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IonicCurrents

IonicConductances

SynapticCurrents

Connectivity

Morphology

FiringProperties

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Neurons.ID Literature Ref.

AJ96

Multiple channel types contribute to the low-voltage-activated calcium current
in hippocampal CA3 pyramidal neurons

1996

Hippocampal neurons exhibit low-voltage-activated (LVA) and
high-voltage-activated (HVA) calcium currents. We characterized the LVA
current by recording whole-cell Ca2+ currents from acutely isolated rat
hippocampal CA3 pyramidal neurons in 2 mM Ca2+. Long depolarizing steps to -50
mV revealed two components to the LVA current: transient and sustained. The
transient phase had a fast decay time constant of 59 msec. The sustained phase
persisted throughout the depolarization, even for steps lasting several
seconds. The transient current was inhibited by the classic T-type channel
antagonists Ni2+ and amiloride. The anticonvulsant phenytoin preferentially
blocked the sustained phase, but ethosuximide had no effect. Steady-state
inactivation of the transient component was half-maximal at -80 mV.
Nimodipine, an L-type channel antagonist, partly inhibited the sustained
current. BayK-8644, an L-type channel agonist, potentiated the sustained
current. Calciseptine, another L-type channel antagonist, inhibited the
sustained component. omega-Conotoxin-MVIIC, a nonselective toxin for HVA
channels, had no effect on either of the LVA current components.
omega-Grammotoxin-SIA, another nonselective toxin, partially inhibited the
sustained component. The voltage dependence of activation of the
nimodipine-sensitive current could be fit with a single Boltzmann, consistent
with a homogenous population of L-type channels in CA3 neurons. Half-maximal
activation of the nimodipine-sensitive current occurred at -30 mV,
considerably more negative than the remaining HVA current. These results
suggest that in physiologic Ca2+ more than one type of Ca2+ channel
contributes to the LVA current in CA3 neurons. The transient current is
carried by T-type channels. The sustained current is carried, at least in
part, by dihydropyridine-sensitive channels. Thus, the designation
"low-voltage-activated" should not be limited to T-type channels.
These findings challenge the traditional designation of L-type channels as
exclusively HVA and reveal a possible role in subthreshold Ca2+ signaling.

DATA NOT ENTERED: Hippocampal cells.

JDJ

AJ96

ASC93a

Postnatal development of a persistent Na+ current in pyramidal neurons from rat
sensorimotor cortex

1993

1. Whole-cell recordings were performed on acutely isolated pyramidal neurons
from rat sensorimotor cortex 2 to 21 days postnatal to study the expression of
a tetrodotoxin (TTX) sensitive, voltage dependent, persistent Na+ current
(INaP) during different stages of postnatal development. 2. INaP was activated
positive to about -60 mV and attained its peak amplitude between -40 and -35
mV. Activation of INaP did not require preceding activation of the transient
Na+ current. 3. Peak INaP amplitudes showed a three-fold increase over the
first three postnatal weeks, starting from 60.7 +/- 7.5 (SE) pA (n = 6) at
postnatal day (P) 2-P5 and reaching 189.1 +/- 20.4 pA (n = 13) at P17-P21. 4.
Measurements of peak INaP density, which took concomitant cell growth into
account, revealed that a considerable current density already existed in very
young neurons (P2-P5: 4.3 +/- 1.0 microA/cm2, n = 6) when compared with INaP
density in early adult neurons (P17 - P21: 8.9 +/- 0.8 microA/cm2, n = 5). 5.
Our data provide the first direct evidence for the presence of a significant
INaP density during early postnatal development of neocortical neurons
indicating that this current should play a role in the control of intrinsic
excitability at this age.

JDJ

ASC93a

-1020917390

481039627

ASC93b

Modal gating of Na+ channels as a mechanism of persistent Na+ current in
pyramidal neurons from rat and cat sensorimotor cortex.

1993

The kinetic behavior of brain Na+ channels was studied in pyramidal cells from
rat and cat sensorimotor cortex using either the thin slice preparation or
acutely isolated neurons. Single-channel recordings were obtained in the
cell-attached and inside-out configuration of the patch-clamp technique. Na+
channels had a conductance of about 16 pS. Patches always contained several
Na+ channels, usually 4-12. In both preparations, long depolarizing pulses
revealed two distinct patterns of late Na+ channel activity following
transient openings. (1) Na+ channels displayed sporadic brief late openings
sometimes clustered to "minibursts" of 10-40 msec. These events
occurred at a low frequency, yielding open probability (NPo) values below 0.01
(mean = 0.0034). (2) In the second gating mode, an individual Na+ channel in
the patch failed to inactivate and produced a burst of openings often lasting
to the end of the pulse. This behavior was observed in about 1% of
depolarizations. Shifts to the bursting mode were usually confined to a single
400 msec pulse, but rarely occurred during two or more consecutive pulses
applied at 2 sec intervals. Sustained bursts did not require preceding
transient openings to occur since they were also observed during slow
depolarizing voltage ramps. The similar incidence of inactivation failures in
cell-attached versus inside-out recordings suggests that the bursting mode is
a property of the channel and/or adjacent membrane-bound structures.
Calculations indicate that brief late openings and rare sustained bursts
suffice to generate a small but significant whole-cell current. Since the Na+
channels mediating early, brief late, and sustained openings were identical in
terms of their elementary electrical properties, we propose that the fast and
the persistent Na+ currents of cortical pyramidal cells are generated by an
electrophysiologically uniform population of Na+ channels that can
individually switch between different gating modes.

DATA NOT ENTERED: Primarily single channel kinetics. NaF/NaP two states of one
channel population.

JDJ

ASC93b

B00b

Distribution and activation of voltage-gated potassium channels in
cell-attached and outside out patches from large layer 5 cortical pyramidal
neurons of the rat.

2000

Voltage-gated potassium channels were studied in cell-attached and outside-out
patches from the soma and primary apical dendrite of large layer 5 pyramidal
neurons in acute slices of rat sensorimotor cortex (22-25 degrees C). Ensemble
averages revealed that some patches contained only fast, I(A)-like channels,
other contained only I(K)-like channels that did not inactivate or inactivated
slowly, and the remainder contained mixtures of both types. I(A) and I(K)
channels had mean unitary conductances of 8.5 and 20.3 pS, respectively, and
had distinctive patterns of gating. Peak activation curves for
ensemble-averaged currents were described by the Boltzmann equation with
half-maximal voltage [V(1/2)] and slope factor (k) values of -24.5 mV and 16.9
mV for I(A) and -7.6 mV and 10.1 mV for I(K) (patches < 250 microm from the
soma) or -22.9 mV and 16.2 mV for I(A) (patches > 250 microm from the
soma). The steady-state inactivation curve for I(A) gave V(1/2) and k values
of -72.3 mV and -5.9 mV (< 250 microm from the soma) or -83.1 mV and -6.5
mV (> 250 microm from the soma). These values were similar to the
corresponding data for I(A) and I(K) in nucleated patches from the same cell.
The amount of I(A) and I(K) present in patches depended weakly on distance
along the primary apical dendrite from the soma. The amplitude of I(A)
increased, on the average, by 2.3 pA per 100 microm, while the amplitude of
I(K) decreased by 0.4 pA per 100 microm. I(A) and I(K) channels in dendritic
cell-attached patches were activated by the passage of a back-propagating
action potential past the tip of the patch electrode. These results show
directly that these potassium channels participate in action potential
repolarisation, and thus contribute to the process of synaptic integration in
these neurons.

JDJ

B00b

1006622979

-625879160

BGC00

A network of electrically coupled interneurons drives synchronized inhibition
in neocortex.

2000

The neocortex has at least two different networks of electrically coupled
inhibitory interneurons: fast-spiking (FS) and low-threshold-spiking (LTS)
cells. Agonists of metabotropic glutamate or acetylcholine receptors induced
synchronized spiking and membrane fluctuations, with irregular or rhythmic
patterns, in networks of LTS cells. LTS activity was closely correlated with
inhibitory postsynaptic potentials in neighboring FS interneurons and
excitatory neurons. Synchronized LTS activity required electrical synapses,
but not fast chemical synapses. Tetanic stimulation of local circuitry induced
effects similar to those of metabotropic agonists. We conclude that an
electrically coupled network of LTS interneurons can mediate synchronized
inhibition when activated by modulatory neurotransmitters.

JDJ

BGC00

-1195798297

-990651240

BSC93

Voltage dependence and activation kinetics of pharmacologically defined
components of the high-threshold calcium current in rat neocortical neurons.

1993

1. As a first step toward identification of the functional significance of the
spatial distribution of calcium channels we examined the high
voltage-activated calcium current (HVA current) in acutely isolated pyramidal
neurons from rat sensorimotor cortex using whole-cell voltage clamp. The goals
of this study were (1) to determine whether the pharmacologically separable
components of the HVA current differed in voltage dependence or activation
kinetics and (2) to develop an empirical model that could predict the HVA
current evoked by action potentials or other physiological responses. 2. Cells
with short dendrites were chosen for study. Input resistance averaged 3.5 +/-
0.4 (SE) G omega. Specific membrane resistance averaged 51.9 +/- 6.8 K
omega-cm2 on the basis of estimated membrane surface area. 3. Using 2 mM
calcium in the extracellular solution, we evoked the HVA current by
depolarizations positive to -45 mV from a holding potential of -60 mV, a
potential where the low-threshold calcium current is fully inactivated.
Maximum HVA current amplitude (484.9 +/- 42.3 pA) occurred near -15 mV. The
evoked current was completely and reversibly blocked by 200 microM cadmium. 4.
Tail current amplitude at a fixed potential increased as a sigmoidal function
of prepulse potential. A plot of normalized tail current amplitude, taken as
the fraction of HVA channels open at each prepulse potential, was best
described by a Boltzmann function (maximum slope: e-fold per 11.3 mV; half
activation: -24.6 mV) raised to the power of 2. This relation was not altered
by extracellular application of 5 microM nifedipine or 10 microM
omega-conotoxin, each of which reduced a separate component of the HVA current
uniformly at all potentials. We conclude that the pharmacologically separable
components of the HVA current do not differ significantly in voltage
dependence. 5. The time course of current onset during a step depolarization
was best described by second-order activation kinetics. Activation time
constants ranged from a maximum of 1.2 ms at -40 mV to 0.3 ms at +25 mV.
Neither activation nor tail current time constants were altered by
extracellular application of 5 microM nifedipine or 10 microM omega-conotoxin.
After application of 1 microM Bay K 8644 tail current decay was best described
by a fast time constant similar to control values and a slow time constant. We
conclude that the pharmacologically separable components of the HVA current in
these neurons do not differ significantly in kinetics.(ABSTRACT TRUNCATED AT
400 WORDS)

JDJ

BSC93

315966505

1004375359

BSC94

Different voltage dependence of transient and persistent Na+ currents is
compatible with modal-gating hypothesis for sodium channels.

1994

1. These experiments tested the hypothesis that the differing voltage
dependence of the transient (INa) and persistent (INaP) Na+ currents in
neocortical neurons results from the state of inactivation of one type of Na+
channel rather than from the existence of different types of Na+ channels.
This question was examined in acutely isolated pyramidal neurons from the
sensorimotor cortex of rats by using papain to remove inactivation from INa
and comparing the resulting activation curve with that of INaP. 2. In control
cells, INaP activated at more negative potentials than INa. Inclusion of
papain in the recording pipette removed inactivation from INa and caused the
INa activation curve to be shifted leftward to the position of the curve for
INaP measured in control cells. Papain greatly increased both INa amplitude
and the time to reach peak INa during smaller depolarizations, whereas the
difference between control and test currents was reduced during large
depolarizations. 3. We conclude that differences in the voltage dependence of
INa and INaP activation does not provide sufficient evidence that these
currents flow through separate sets of Na+ channels. Instead, our results are
consistent with the idea that INaP largely arises from a fraction of the
transient Na+ channels that intermittently lose their inactivation.

JDJ

BSC94

-1756532732

406866101

BSSC94

P-type calcium channels in rat neocortical neurones

1994

1. The high threshold, voltage-activated (HVA) calcium current was recorded
from acutely isolated rat neocortical pyramidal neurones using the whole-cell
patch technique to examine the effect of agents that block P-type calcium
channels and to compare their effects to those of omega-conotoxin GVIA
(omega-CgTX) and nifedipine. 2. When applied at a saturating concentration
(100 nM) the peptide toxins omega-Aga-IVA and synthetic omega-Aga-IVA blocked
31.5 and 33.0% of the HVA current respectively. 3. A saturating concentration
of nifedipine (10 microM) inhibited 48.2% of the omega-Aga-IVA-sensitive
current, whereas saturating concentrations of both omega-Aga-IVA (100 nM) and
omega-CgTX (10 microM) blocked separate specific components of the HVA
current. 4. Partially purified funnel web spider toxin (FTX) at a dilution of
1:1000 blocked 81.4% of the HVA current and occluded the inhibitory effect of
omega-Aga-IVA. Synthetic FTX 3.3 arginine polyamine (sFTX) at a concentration
of 1 mM blocked 61.2% of the HVA current rapidly and reversibly. The effects
of sFTX were partially occluded by pre-application of omega-Aga-IVA. We
conclude that neither FTX nor sFTX blocked a specific component of the HVA
current in these cells. 5. In view of the specificity of omega-Aga-IVA for
P-type calcium channels in other preparations and for a specific component of
the HVA current in dissociated neocortical neurones we conclude that about 30%
of the HVA current in these neurones flow through P-channels.

JDJ

BSSC94

996239748

-1041488843

CG90

Intrinsic firing patterns of diverse cortical neurons

1990

Neurons of the neocortex differ dramatically in the patterns of action
potentials they generate in response to current steps. Regular-spiking cells
adapt strongly during maintained stimuli, whereas fast-spiking cells can
sustain very high firing frequencies with little or no adaptation.
Intrinsically bursting cells generate clusters of spikes (bursts), either
singly or repetitively. These physiological distinctions have morphological
correlates. RS and IB cells can be either pyramidal neurons or spiny stellate
cells, and thus constitute the excitatory cells of the cortex. FS cells are
smooth or sparsely spiny non-pyramidal cells, and are likely to be GABAergic
inhibitory interneurons. The different firing properties of neurons in
neocortex contribute significantly to its network behavior.

DATA NOT ENTERED: General interest review, hypothesis, qualitative data.

JDJ

CG90

FG96

Kinetics of slow inactivation of persistent sodium current in layer V neurons
of mouse neocortical slices.

1996

1. In whole cell recordings from layer V neurons in slices of mouse
somatosensory neocortex, tetrodotoxin (TTX)-sensitive persistent Na+ current
(INaP) was studied by blocking K+ currents with intracellular Cs+ and Ca2+
currents with extracellular Cd2+. During slow voltage ramps, INaP began to
activate at around -60 mV, and attained a peak at around -25 mV. The peak
amplitude of INaP varied widely from cell to cell (range 60-3,160 pA; median
308 pA, n = 77). At potentials more positive than -35 mV, INaP in all cells
was superimposed on a large, TTX-resistant outward current. 2. In hybrid clamp
experiments, INaP was significantly reduced by a preceding high-frequency
train of spikes. 3. INaP underwent pronounced slow inactivation, which was
revealed by systematically varying the ramp speed between 233 and 2.33 mV/s,
or varying the duration of a depolarizing prepulse between 0.1 and 10 s. 4.
Onset of slow inactivation at +20 mV was monoexponential with tau = 2.06 s (n
= 17 cells). Recovery from slow inactivation was voltage dependent. It
followed a monoexponential time course with tau = 2.31 s (n = 6) at -70 mV and
tau = 1.10 s (n = 4) at -90 mV. These values are not significantly different
than values previously reported for slow inactivation of fast-inactivating
INa. 5. Slow inactivation of neocortical INaP will influence all neuronal
functions in which this current plays a role, including spike threshold
determination, synaptic integration, and active propagation in dendrites. The
kinetics of slow inactivation suggest that it may be a factor not only during
extremely intense spiking, but also during periods of "spontaneous"
activity.

JDJ

FG96

988800474

-1725086893

FGPSWA95

Ionic mechanisms underlying burst firing in pyramidal neurons: intracellular
study in rat sensorimotor cortex.

1995

In in vitro slices prepared from rat sensorimotor cortex, intracellular
recordings were obtained from 107 layer V pyramidal neurons, subsequently
injected with biocytin for morphological reconstruction. Of the 107 neurons,
59 (55.1%) were identified as adapting (45) or non-adapting (13) regular
spiking neurons (RS), and 48 (44.9%) as intrinsically bursting (IB) neurons
discharging with an initial cluster of action potentials, which tended to
recur rhythmically in a subset of 19 cells. The block of IAR by extracellular
Cs+ did not affect burst generation, but enhanced the tendency to reburst in
IB neurons. A similar effect was induced by other procedures affecting
K(+)-dependent post-burst hyperpolarization. In IB neurons Ca2+ spikes had a
longer decay time than in RS neurons, however selective blockers of both low
and high threshold Ca2+ conductances failed to impair bursting activity. On
the contrary, the perfusion of the slices with 0.5-1 microM TTX suppressed
bursting behaviour in a critical time interval preceding the complete block of
Na(+)-dependent action potentials. It is concluded that the persistent Na+
current INAP is the most important intrinsic factor for the typical firing
properties of IB neurons, while Ca2+ and K+ conductances appear to contribute
towards shaping bursts and controlling their recurrence rate. The morphology,
connectivity and physiological properties of adapting and non-adapting RS
neurons are particularly suited to the processing of respectively phasic and
tonic inputs, whereas the properties of IB neurons are consistent with their
suggested role in cortical rhythmogenesis and in the pathophysiological
synchronized activities underlying epileptogenesis.

JDJ

FGPSWA95

-399777519

996756505

FSPRA98

Postnatal differentiation of firing properties and morphological
characteristics in layer V pyramidal neurons of the sensorimotor cortex.

1998

The maturational profile of the firing characteristics of 217 layer V pyramidal
neurons of rat sensorimotor cortex, injected with biocytin for morphological
reconstruction, was analysed by means of intracellular recordings made between
postnatal day (P)3 and 22. Starting from the onset of the second postnatal
week, the pyramidal neurons could be differentiated as adapting or
non-adapting regular spiking on the basis of the presence or absence of spike
frequency adaptation. The percentage of non-adapting regular spiking neurons
was very high during the second postnatal week (53%) and progressively
decreased with age, concurrently with the appearance of the new class of
intrinsically bursting neurons (beginning of the third week) whose percentage
progressively increased from 23%, found in P14-P16 rats, to 46% in adult rats.
Non-adapting regular spiking neurons were found to share with intrinsically
bursting neurons several physiological characteristics comprehending faster
action potentials, more prominent effect of anomalous rectification and
consistent depolarizing afterpotentials, that differentiated them from the
adapting regular spiking neurons. Moreover, intrinsically bursting and
non-adapting regular spiking neurons were characterized by a round-shaped
distribution of basal dendrites and expanded apical dendritic arborization,
that differentiated them from the adapting regular spiking neurons showing a
simpler dendritic arborization. These morphological hallmarks were seen in
immature intrinsically bursting neurons as soon as they became
distinguishable, and in immature non-adapting regular spiking neurons starting
from the onset of the second postnatal week. These findings suggest that a
significant subpopulation of immature non-adapting regular spiking neurons are
committed to becoming bursters, and that they are converted into intrinsically
bursting neurons during the second postnatal week, as soon as the ionic
current sustaining the burst firing is sufficiently strong. The faster action
potentials in both immature non-adapting regular spiking and intrinsically
bursting neurons suggest a higher density of Na+ channels in these neuronal
classes: the maturational increase in Na+-current, namely of its persistent
fraction, may represent the critical event for the conversion of the
non-adapting regular spiking neurons into the intrinsically bursting ones.

Data from adult neurons entered.

JDJ

FSPRA98

999097811

999248438

General Map

2000

General map for identifying areas, layers, neurons and compartments.

JDJ

H96

Low-threshold calcium currents in central nervous system neurons.

1996

The low-threshold calcium current, or T current, has recently been demonstrated
with voltage-clamp recordings in a variety of central nervous system (CNS)
neurons. It is especially prominent in the soma and dendrites of neurons with
robust calcium-dependent burst firing behaviors such as thalamic relay neurons
and cerebellar Purkinje cells. Single-channel and macroscopic current behavior
have been carefully investigated and kinetic schemes devised to completely
describe the activation and inactivation processes. The kinetic properties of
T current lead to activation of low-threshold spikes subsequent to transient
membrane hyperpolarizations. Putative functional roles for T current include
generation of low-threshold spikes that lead to burst firing, promotion of
intrinsic oscillatory behavior, boosting of calcium entry, and synaptic
potentiation.

DATA NOT ENTERED: Comparative review on biophysical properties, pharmacology,
localization and function of T-type calcium current. Very few data from
neocortical preparations.

JDJ

H96

HHP88

Developmental Changes in Na+ Conductances in Rat Neocortical Neurons:
Appearance of a Slowly Inactivating Component

1988

1. Na+ conductances have been characterized in rat neocortical neurons from the
sensorimotor area. Neurons were obtained by acute dissociation from animals at
developmental stages from embryonic day 16 (E16) to postnatal day 50 (P50) to
quantify any developmental changes in the kinetic properties of the Na+
conductance. 2. Neurons were divided into two classes, based on morphology, to
determine whether there are any cell-type specific differences in Na+
conductances that contribute to the different action potential morphologies
seen in current-clamp recordings in vitro. 3. Upon isolation, neurons were
voltage clamped using the whole-cell variation of the patch-clamp technology.
Both cell types, pyramidal and nonpyramidal, demonstrate large increases in
Na+ current density during this developmental period (E16-P50). Normalized
conductances were near 10 pS/micron2 in neurons from embryonic animals, and
increased 6- to 10-fold during the first 2 wk postnatal. The final conductance
reached in pyramidal neurons was higher than in non-pyramidal neurons. 4. We
found no differences between the two cell types, pyramidal and nonpyramidal,
in the voltage dependence of activation, inactivation kinetics, voltage
dependence of steady-state inactivation, and recovery from inactivation. 5.
The time course of Na+ current in immature neurons were fit with classical
Hodgkin-Huxley kinetics. However, in more mature neurons the kinetics of
inactivation became more complicated such that two decay components were
required to obtain good fit. The slowly decaying component had a time course 5
to 10 times slower than the fast component. 6. Several procedures were used to
reduce the magnitude of Na+ conductance in mature neurons to ensure graded,
voltage-dependent inward currents. These included reduced extracellular [Na+],
submaximal tetrodotoxin concentrations, and reduced holding potential. Under
each of these conditions we were able to verify the observation that Na+
current inactivation occurs with two exponentials. 7. Single-channel Na+
currents were obtained from cell-attached patches. The membrane density of
active Na+ channels increases with development, and ensemble averages from
mature neurons demonstrated two inactivation processes. The slow inactivation
process was accounted for by long-latency single-channel openings of the same
amplitude as the short-latency openings. 8. We conclude that there are no
kinetic differences in the Na+ channels between cell types. Differences in
action potentials are then not explained by differences in Na+ current
kinetics, but might be partially explained by the different
densities.(ABSTRACT TRUNCATED AT 400 WORDS)

JDJ

HHP88

-20718951

35614620

HHP89

Sodium channels in dendrites of rat cortical pyramidal neurons.

1989

The voltage-dependent properties that have been directly demonstrated in
Purkinje cell and hippocampal pyramidal cell dendrites play an important role
in the integrative capacities of these neurons. By contrast, the properties of
neocortical pyramidal cell dendritic membranes have been more difficult to
assess. Active dendritic conductances near sites of synaptic input would have
an important effect on the input-output characteristics of these neurons. In
the experiments reported here, we obtained direct evidence for the existence
of voltage-dependent Na+ channels on the dendrites of neocortical neurons by
using cell-attached patch and whole cell recordings from acutely isolated rat
neocortical pyramidal cells. The qualitative and quantitative properties of
dendritic and somatic currents were indistinguishable. Insofar as Na+ currents
are concerned, the soma and primary apical dendrite can be considered as one
relatively uniform compartment. Similar dendritic Na+ currents on dendrites in
mature neurons would play an important role in determining the integrative
properties of these cortical units.

JDJ

HHP89

-232296371

-9806123

HHP91

Patch-clamp studies of voltage-gated currents in identified neurons of the rat
cerebral cortex

1991

In the cerebral cortex, neurons can be classified into 2 broad morphological
classes, referred to as pyramidal and nonpyramidal (stellate) cells, which
correspond to functional classes of projection neurons and local circuit
interneurons, respectively. In this study, we demonstrate that specific
morphological, immunohistochemical, and physiological features, that allow
class distinction of neurons in situ, are retained in acutely isolated
neocortical neurons. Furthermore, voltage-clamp analysis with patch-clamp
techniques indicate the differences in functional properties in adult neurons,
reflect cell-specific, developmental changes in the density and type of
specific classes of Na+, K+ and Ca2+ channels expressed. The differences in
channel properties contribute to the different input-output relations of
neocortical neurons, which enable inhibitory neurons to follow excitatory
inputs faithfully and projection neurons to have more integrative roles.

JDJ

HHP91

-862865877

216257617

KHP96a

Development of BK channels in neocortical neurons.

1996

1. Postnatal development of a large conductance Ca(2+)-activated K+ channel (BK
channel) was investigated in neocortical infragranular pyramidal neurons with
inside-out and outside-out patchclamp configurations. Neurons were acutely
isolated from slices of 1- to 28-day-old rats (P1-P28) by using a vibrating
glass probe after preincubation with low concentrations of enzymes. Patch
membrane area was estimated by measuring membrane capacitance. The density,
distribution, voltage dependence, Ca2+ sensitivity, kinetics, and
pharmacological properties of BK channels were examined in neurons from
animals of different ages. 2. In somata, the density of BK channels was 0.056
+/- 0.011/ micron 2 in P1 neurons and 0.312 +/- 0.008/micron 2 in P28 neurons.
There was an abrupt increase between P5 and P7 at a rate of approximately
0.042/ micron 2/day. Before P5 and after P7, the density of BK channels also
increased but at slower rates. 3. The density of BK channels in proximal
apical dendrites underwent a similar developmental sequence. There was a
relatively large increase between P5 and P7 with a rate of approximately
0.021/ micron 2/day, and after P7, channel density increased more slowly
(approximately 0.002/microns 2/day). In P1 neurons, channel density in apical
dendrites was 0.039 +/- 0.008/micron 2, which was close to that in somata,
whereas in P28 neurons, channel density (0.134 +/- 0.008/micron 2) was less
than one-half of that in somata. 4. The distribution of BK channels was
different in immature and mature neurons. In somata of P1 neurons, BK channels
were distributed singly without evidence of clustering, whereas in P28 neurons
BK channels were clustered in groups of approximately 4. 5. BK channels in
both P1 and P14 neurons showed a steep increase in the probability of opening
(Po) as intracellular Ca2+ concentration was raised from 50 to 100 nM,
especially at positive membrane potentials. The Ca2+ dependence, as measured
by the [Ca2+]i that provided half-maximal Po at a variety of membrane
potentials, was not different in patches from P1 and P14 neurons. On the other
hand, the voltage dependence of BK channels shifted during ontogeny such that
Po was larger at negative potentials in P14 than in P1 neurons. 6. The voltage
dependence of P1 BK channels was bimodally distributed with 57% of channels
exhibiting an "immature" pattern consisting of a more positive V1/2
and a smaller change in voltage required to produce an e-fold increase in Po.
Immature type P1 BK channels showed a longer mean closed time at negative
membrane potentials than either P14 or "mature" P1 BK channels. 7.
No postnatal developmental changes in pharmacological properties of BK
channels were observed. In both mature and immature neurons, BK channels were
partially inhibited by 30 or 100 nM charybdotoxin (ChTX) and fully blocked by
1 microM ChTX. The IC50 for ChTX was 100 nM, indicating that BK channels in
neocortical pyramidal neurons are much less sensitive to ChTX than those in
muscle cells and sympathetic ganglion neurons. BK channels were also inhibited
by 0.5 mM tetraethylammonium chloride (TEA) and 50 microM trifluoperazine. 8.
These data indicate that functional somatic and dendritic BK channels are
inserted into neuronal membranes during neocortical development, with an
especially rapid increment in density occurring around P5-P7. These changes,
which occur at a time when other voltage-gated ion channels are known to be
increasing in density, contribute to the development of neocortical
excitability.

JDJ

KHP96a

-1135746851

-2090324328

KHP96b

Two types of BK channels in immature rat neocortical pyramidal neurons

1996

1. The properties of large conductance Ca(2+)-activated K+ channels (BK
channels) were investigaed in neocortical infragranular pyramidal neurons by
the use of inside-out patch recordings. Neurons were acutely isolated from
slices of newborn to 28-day-old rats (P0-P28) by using minimal protease
exposure followed by trituration with a vibrating glass probe. Two types of BK
channels, slow-gating and fast-gating, were observed in immature neurons
(P0-P5), whereas only slow-gating BK were found in more mature neurons.
Fast-gating BK channels differed in conductance, voltage dependence, and
kinetics from the slow-gating ones. 2. The properties of fast-gating channels
included a conductance of 145 +/- 12.9 (SE) pS; frequent openings with short
mean open times that were relatively voltage-independent, mean closed times
that showed a voltage-dependent increase, a voltage-dependent decrease in open
probability (Po). The properties of slow-gating channels contrasted with those
of the fast-gating ones, in that the former had a conductance of 181 +/- 3.9
pS, longer mean open times that showed a voltage-dependent increase, mean
closed times that showed a marked voltage-dependent decrease, a
voltage-dependent increase in Po, and slight inward rectification. The
significance of these developmental variations in channel properties is
discussed.

Rapid communication. Only data on slow BK counductance (present in adult
neurons) entered.

JDJ

KHP96b

998918972

998919415

KLLB94a

Pyramidal neurons in layer 5 of the rat visual cortex. I. Correlation among
cell morphology, intrinsic electrophysiological properties, and axon targets.

1994

Previous work has established two structure/function correlations for pyramidal
neurons of layer 5 of the primary visual cortex of the rat. First, cells
projecting to the superior colliculus have thick apical dendrites with a
florid terminal arborization in layer 1, whereas those projecting to the
visual cortex of the opposite hemisphere have thinner apical dendrites that
terminate below layer 1, without a terminal tuft (e.g., Hallman et al.: J Comp
Neurol 272:149, '90). Second, intracellular recording combined with dye
injection has revealed two classes of cells: the first has a thick, tufted
apical dendrite and fires a distinctive initial burst of two or more impulses,
of virtually fixed, short interspike interval, in response to current
injection; and the other, with a slender apical dendrite lacking a terminal
tuft, tends to have a longer membrane time constant and higher input
resistance, and does not fire characteristic bursts (e.g., Larkman and Mason:
J Neurosci 10:1407, '90). The present study combined intracellular recording
in isolated slices of rat visual cortex and injection of carboxyfluorescein,
to reveal soma-dendritic morphology, with prior injection of
rhodamine-conjugated microspheres into the superior colliculus or
contralateral visual cortex to label neurons according to the target of their
axons. This permitted a complete correlation of morphology, intrinsic
electrophysiological properties, and identity of the projection target for
individual pyramidal cells. Neurons retrogradely labeled from the opposite
visual cortex were found in all layers except layer 1 while those labeled from
the superior colliculus lay exclusively in layer 5. Within layer 5
interhemispheric cells were more concentrated in the lower half of the layer
but extensively overlapped the distribution of corticotectal cells. Every cell
studied that projected to the superior colliculus was of the bursting type and
had a thick apical dendrite with a terminal tuft. Every cell in this study
projecting to the opposite visual cortex was a "nonburster" and had
a slender apical dendrite with fewer oblique branches that ended without a
terminal tuft, usually in the upper part of layer 2/3. Interhemispheric cells
also had rounder, less conical somata and generally had fewer basal dendrites
than corticotectal neurons. Many cells with the physiological and
morphological characteristics of interhemispheric cells were not back-labeled
from the opposite visual cortex, implying that pyramidal cells of this type
can have other projection targets (e.g., other cortical sites in the
ipsilateral hemisphere).(ABSTRACT TRUNCATED AT 400 WORDS)

Data on firing properties entered.

JDJ

KLLB94a

998925852

998993756

KLLB94b

Pyramidal neurons in layer 5 of the rat visual cortex. II. Development of
electrophysiological properties.

1994

Two major classes of pyramidal neurons can be distinguished in layer 5 of the
adult rat visual cortex. Cells of the "thick/tufted" type have stout
apical dendrites with terminal tufts, and most of them project to the superior
colliculus (Larkman and Mason: J Neurosci 10:407, '90; Kasper et al.: J Comp
Neurol, this issue, 339:459-474). "Slender/untufted" cells have
thinner apical trunks with no obvious terminal tufts, and a substantial
proportion of them project to the contralateral visual cortex. These two types
also differ in their intrinsic electrophysiological features. In this study we
describe the postnatal maturation of the electrophysiological and synaptic
properties of layer 5 pyramidal neurons and relate these findings to the
morphological development and divergence of the two cell types. Living slices
were prepared from the visual cortex of rats aged between postnatal day 3 (P3)
and young adults and maintained in vitro. Stable intracellular impalements
were obtained from a total of 63 pyramidal cells of layer 5 at various ages,
which were injected with biocytin so that morphological and
electrophysiological data could be obtained from the same cell. Before P15,
injection of a single cell sometimes stained a cluster of neurons of similar
morphology, probably as a result of dye coupling. The incidence of such
clustering and the number of neurons within each cluster decreased with age.
There was no obvious difference in electrophysiological properties between
cells in clusters and age-matched, noncoupled neurons. From P5, the apical
dendrites of neurons could easily be classified as "thick/tufted" or
"slender/untufted." On average, the resting potential became more
negative, and membrane time constant and input resistance decreased with age.
Electrophysiological differences between the "thick/tufted" and
"slender/untufted" cell types did not become apparent until the
third postnatal week, after which the "thick/tufted" cells on
average had lower input resistances and slightly faster time constants than
"slender/untufted" cells. The current-voltage relations of the
neurons became progressively more nonlinear during maturation, with both rapid
inward rectification and time-dependent rectification or "sag"
becoming more prominent. There were also changes in the amplitude and waveform
of action potentials, which generally approached adult values by 3 weeks of
age. Action potential threshold became more negative, both in absolute terms
and relative to the resting membrane potential. Action potentials became
larger in peak amplitude and of shorter duration, with both rise and fall
times decreasing progressively during development.(ABSTRACT TRUNCATED AT 400
WORDS)

DATA NOT ENTERED: Developmental issues.

JDJ

KLLB94b

KLLB94c

Pyramidal neurons in layer 5 of the rat visual cortex. III. Differential
maturation of axon targeting, dendritic morphology, and electrophysiological
properties.

1994

This paper describes the early morphological and physiological development of
pyramidal neurons in layer 5 of the rat visual cortex in relation to the
targets chosen by their axons. Cells were prelabeled by retrograde transport
from the superior colliculus or the contralateral visual cortex and
intracellularly injected either in fixed slices or after recording in living
slices. In the adult, corticotectal cells have thick apical dendrites with an
extensive terminal arborization extending into layer 1, and fire
characteristic bursts of action potentials when injected with a depolarizing
current; interhemispheric cells have slender apical dendrites that terminate
without a terminal tuft, usually in layer 2/3, and they display a more regular
firing pattern (Kasper et al.: J Comp Neurol, this issue, 339:459-474). At
embryonic day E18 (when axons of the two classes of cells are already taking
different routes towards their targets) and E21, pyramidal-like cells
throughout the cortical plate all have similar soma-dendritic morphology, with
spindle-shaped cell bodies and few, short basal dendrites but apical dendrites
that all end in distinct tufts in the marginal zone. At postnatal day P3,
after the axons of both cell classes have reached their targets, all pyramidal
neurons in layer 5 still have distinct terminal arborizations in layer 1,
though they vary in complexity and extent. The somata are now more mature
(round to ovoid in shape), and the basal dendritic tree has extended. As early
as P5, all cells studied could be clearly classified as tufted or untufted
(considerably earlier than previously reported; Koester and O'Leary: J
Neurosci 12:1382, '92), and these features correlated precisely with the
projection target, as in the adult. Measurement showed that although
interhemispheric cells lose their terminal tufts, in general the trunks of
their apical dendrites do not withdraw but continue to grow, at roughly the
same rate as those of corticotectal cells. The two classes of layer 5
pyramidal neurons differentiate from each other in three distinct phases:
pathway selection by axons precedes the loss of the apical tuft by
interhemispheric cells, and these morphological characteristics are
established 10 days before the onset of burst-firing in corticotectal cells.
These three steps may be guided by different molecular signals.

DATA NOT ENTERED: Original data on non-mature cells. For mature cells
REF:Larkman & Mason (J Neurosci. 1990 May;10(5), 2 papers) or Larkman (J Comp
Neurol. 1991 Apr 8;306(2)) 3 papers.

JDJ

KLLB94c

KS00

Voltage-gated K+ channels in layer 5 neocortical pyramidal neurones from young
rats: subtypes and gradients.

2000

We investigated the types and distribution of voltage-gated K+ channels in the
soma and apical dendrite of layer 5 (L5) neocortical pyramidal neurones, of
young rats (postnatal days 13-15), in acute brain slices. A slow inactivating
outward K+ current and a fast inactivating outward K+ current were detected in
nucleated patches. The slow K+ current was completely blocked by
tetraethylammonium (TEA) with an IC50 of 5 +/- 1 mM (mean +/- s.e.m.) and was
partially blocked by 4-aminopyridine (4-AP). The fast K+ current was blocked
by 4-AP with an IC50 of 4.2 +/- 0.5 mM, but was not blocked by TEA. The
activation kinetics of the slow K+ current were described by a second order
Hodgkin-Huxley model. The slow K+ current displayed bi-exponential
inactivation. A fourth order Hodgkin-Huxley model for activation and first
order for inactivation described the kinetics of the fast K+ current. In
somatic cell-attached recordings, three classes of single K+ channels could be
differentiated based on their unitary conductance and inactivation kinetics, a
fast inactivating channel having a conductance of 13 +/- 1 pS, a slow
inactivating channel having a conductance of 9.5 +/- 0.5 pS, and a very slowly
inactivating channel having a conductance of 16 +/- 1 pS. The inactivation
time constants of the slow and of the very slow K+ channel corresponded to the
two inactivation time constants of the slow K+ current observed in nucleated
patches. This suggested that two distinct K+ channels mediated the slow K+
current in nucleated patches. The three subtypes of K+ channels that were
observed in somatic recordings were present along the apical dendrite. The
amplitude of ensemble K+ currents in cell-attached patches decreased along the
apical dendrite as the distance from the soma increased, with a slope of -0.9
+/- 0.3 pA per 100 microm. The results suggest that the decrease of the
voltage-gated K+ channel density from the soma along the apical dendrite of L5
pyramidal neurones helps to define a distal, low threshold region for the
initiation of dendritic regenerative potentials.

JDJ

KS00

-2086957548

1006790213

LESF00

Columnar organization of dendrites and axons of single and synaptically coupled
excitatory spiny neurons in layer 4 of the rat barrel cortex.

2000

Cortical columns are the functional units of the neocortex that are
particularly prominent in the "barrel" field of the somatosensory
cortex. Here we describe the morphology of two classes of synaptically coupled
excitatory neurons in layer 4 of the barrel cortex, spiny stellate, and star
pyramidal cells, respectively. Within a single barrel, their somata tend to be
organized in clusters. The dendritic arbors are largely confined to layer 4,
except for the distal part of the apical dendrite of star pyramidal neurons
that extends into layer 2/3. In contrast, the axon of both types of neurons
spans the cortex from layer 1 to layer 6. The most prominent axonal
projections are those to layers 4 and 2/3 where they are largely restricted to
a single cortical column. In layers 5 and 6, a small fraction of axon
collaterals projects also across cortical columns. Consistent with the dense
axonal projection to layers 4 and 2/3, the total number and density of boutons
per unit axonal length was also highest there. Electron microscopy combined
with GABA postimmunogold labeling revealed that most (>90%) of the synaptic
contacts were established on dendritic spines and shafts of excitatory neurons
in layers 4 and 2/3. The largely columnar organization of dendrites and axons
of both cell types, combined with the preferential and dense projections
within cortical layers 4 and 2/3, suggests that spiny stellate and star
pyramidal neurons of layer 4 serve to amplify thalamic input and relay
excitation vertically within a single cortical column.

Discussion of "Flow of excitation in the barrel cortex".

JDJ

LESF00

-1143564358

-2088194568

LF95a

Characterization of pharmacologically identified voltage-gated calcium channel
currents in acutely isolated rat neocortical neurons. I. Adult neurons

1995

1. Whole cell recordings were obtained from pyramidal neurons acutely
dissociated from the sensorimotor cortex of adult rats. 2. Whole cell calcium
channel currents were similar in appearance when elicited from holding
potentials of -90 or -40 mV. With 5 mM Ba2+ as the charge carrier, currents
began to activate at approximately -45 mV, peaked at approximately -10 mV, and
had an apparent reversal potential of approximately +45 mV. Current amplitude
and voltage dependence varied with the concentration and identity of the
charge carrier (Ca2+ vs. Ba2+). Calcium channel currents were blocked
completely by > 200 microM Cd2+ (IC50 approximately 3.5 microM). 3. We
determined saturating doses for blockade of currents by nifedipine (Nif),
omega-conotoxin GVIA (CgTx), and omega-agatoxin IVA (AgTx) in adult cells. We
also tested the selectivity of these compounds by applying them in combination
and in different orders. We found the three compounds to be highly, but not
perfectly, specific. 4. L-type current was operationally defined as that
blocked by 5 microM Nif, N-type current as that blocked by 1 microM CgTx, and
P-type current as that blocked by 100 nM AgTx. In adult cells, each of these
compounds blocked 30-35% of the current. When all three blockers were applied
concurrently, approximately 80% of the current was blocked (20% of current was
resistant to the 3 blockers). 5. Few biophysical differences were found
between the pharmacologically defined current components in adult cells. The
resistant current had a more rapid time-to-peak, inactivated more rapidly and
completely, and activated at more negative potentials than the other three
types.

JDJ

LF95a

-231029841

999088458

LF95b

Characterization of pharmacologically identified voltage-gated calcium channel
currents in acutely isolated rat neocortical neurons. II. Postnatal
development.

1995

1. Whole cell recordings were obtained from pyramidal neurons acutely
dissociated from the sensorimotor cortex of adult (from Lorenzon and Foehring,
companion paper) and immature rats postnatal day 1 (P1) to adult. 2. Whole
cell calcium channel currents were similar in appearance at all ages. Current
amplitudes and estimated densities were initially low (approximately 16 pA/pF
at ages < P6) and increased gradually, attaining adult values at
approximately 4-5 wk postnatally (approximately 100 pA/pF). 3. L-type current
was operationally defined as that blocked by 5 microM nifedipine, N-type
current as that blocked by 1 microM omega-conotoxin GVIA, and P-type current
as that blocked by 100 nM omega-agatoxin IVA. A resistant current remained in
the presence of the combination of these three blockers. The proportions of
these four current types did not change during ontogeny. 4. Few biophysical
differences were found between the pharmacologically defined current
components in adult or 1-wk-old cells. At both ages the resistant current had
a more rapid time-to-peak and inactivated more completely and rapidly than the
other three types. Resistant currents also activated at more negative
potentials. N-, L-, and P-type currents activated at more positive potentials
in 1-wk-old cells than in adult cells. For the resistant current, the voltage
dependence of activation was not significantly different between the two ages.

DATA NOT ENTERED: Developmental issues.

JDJ

LF95b

MFA98

Anemone toxin (ATX II)-induced increase in persistent sodium current: effects
of the firing properties of rat neocortical pyramidal neurones.

1998

1. The experiments were performed on sensorimotor cortex using current-clamp
intracellular recordings in layer V pyramidal neurones and whole-cell
voltage-clamp recordings in dissociated pyramidal neurones. The
intracellularly recorded neurones were classified on the basis of their firing
characteristics as intrinsically bursting (IB) and regular spiking (RS). The
RS neurones were further subdivided into adapting (RSAD) or non-adapting
(RSNA), depending on the presence or absence of spike frequency adaptation.
Since burst firing in neocortical pyramidal neurones has previously been
suggested to depend on the persistent fraction of Na+ current (INa, p),
pharmacological manipulations with drugs affecting INa inactivation have been
employed. 2. ATX II, a toxin derived from Anemonia sulcata, selectively
inhibited INa fast inactivation in dissociated neurones. In current-clamp
experiments on neocortical slices, ATX II enhanced the naturally occurring
burst firing in IB neurones and revealed the ability of RSNA neurones to
discharge in bursts, whereas in RSAD neurones it increased firing frequency,
without inducing burst discharges. During the ATX II effect, in all the three
neuronal subclasses, episodes of a metastable condition occurred,
characterized by long-lasting depolarizing shifts, triggered by action
potentials, which were attributed to a peak in the toxin-induced inhibition of
INa inactivation. The ATX II effect on IB and RSNA neurones was compared with
that induced by veratridine and iodoacetamide. Veratridine induced a small
increase in the INa and a large shift to the left in the voltage dependence of
INa activation. Accordingly, its major effect on firing characteristics was
the induction of prolonged tonic discharges, associated with burst
facilitation less pronounced than that induced by ATX II. The alkylating agent
iodoacetamide was able to induce a selective small increase in the INa,p, with
a similar but less pronounced effect than ATX II on firing behaviour. 3. The
present results show that pharmacological manipulations capable of slowing
down INa inactivation significantly enhance burst behaviour in IB neurones and
promote burst firing in otherwise non-bursting RSNA neurones. We suggest that
IB and, to a lesser extent, RSNA neurones are endowed with a relatively large
fraction of INa,p which, in physiological conditions, is sufficient to sustain
bursting in IB but not in RSNA neurones.

JDJ

MFA98

-1662948559

989418859

MLSC97

Evidence for persistant Na+ current in apical dendrites of rat neocortical
neurons from imaging of Na+-sensitive dye

1997

Evidence for a persistent Na+ current (I(NaP)) in the apical dendrite of
neocortical neurons was sought with the use of fluorescence imaging to measure
changes in intradendritic Na+ concentration. Neurons in neocortical brain
slices were filled iontophoretically through an intracellular recording
microelectrode with the Na+-sensitive dye benzofuran isophthalate (SBFI), and
fluorescence images were recorded with a cooled charge-coupled device camera
system using 380-nm illumination. In the presence of Ca2+ and K+ channel
blockers, a short depolarizing current pulse evoked a single action potential
followed by a plateau depolarization (PD) lasting >1 s. This tetrodotoxin
(TTX)-sensitive PD is known to be maintained by I(NaP). A single action
potential caused no detectable SBFI fluorescence change, whereas the PD was
associated with an SBFI fluorescence change in the soma and apical dendrite
indicating increased intracellular Na+ concentration. Determination of the
full spatial extent of the dendritic fluorescence change was prevented by our
inability to detect the dim fluorescence signal in the distal regions of the
apical dendrite. In each experiment the fluorescence change extended into the
apical dendrite as far as dye could be visualized (50-300 microm). A slow,
depolarizing voltage-clamp ramp that activated I(NaP) caused similar
fluorescence changes that were eliminated by TTX, indicating that the SBFI
fluorescence changes are caused by Na+ influx due to I(NaP) activation. We
conclude that I(NaP) can be generated by the apical dendritic membrane to at
least 300 microm from the soma.

JDJ

MLSC97

-253258512

-1546107746

OSC01a

Initiation and propagation of regenerative Ca(2+)-dependent potentials in
dendrites of layer 5 pyramidal neurons.

2001

The initiation and propagation of dendritic Ca(2+)-dependent regenerative
potentials (CDRPs) were investigated by imaging the Ca(2+)-sensitive dye
Fluo-4 during whole cell recording from the soma of layer 5 pyramidal neurons
visualized in a slice preparation of rat neocortex by the use of
infrared-differential interference contrast microscopy. CDRPs were evoked by
focal iontophoresis of glutamate at visually identified sites 178-648 microm
from the soma on the apical dendrite and at sites on the basal dendrites.
Increases in [Ca(2+)](i) were maximal near the site of iontophoresis and were
graded with iontophoretic current that was subthreshold for evoking CDRPs.
CDRP initiation was associated with a [Ca(2+)](i) rise that differed from a
just-subthreshold response in both magnitude and spatial extent but whose
amplitude declined both proximal and distal to the iontophoretic site. These
[Ca(2+)](i) rises, whether associated with subthreshold or regenerative
voltage responses, were minimally affected by blockade of N-methyl-D-aspartate
receptors but were abolished by Cd(2+), suggesting that Ca(2+) influx through
voltage-gated channels caused the rise of [Ca(2+)](i). On the assumption that
the rise of [Ca(2+)](i) during a CDRP marks the spatial extent of regenerative
Ca(2+) influx, we conclude that CDRPs can be evoked at any point on the main
apical or basal trunk where membrane potential reaches CDRP threshold rather
than at discrete "hot spots," the CDRP is initiated at a spatially
restricted site, and it propagates decrementally both distal and proximal to
its initiation site. These results raise the possibility that synaptic
integration may occur first in the dendrites to evoke a CDRP. Because these
responses propagate decrementally to the soma, they are able to sum with input
from other regions of the cell so that the cell as a whole remains integrative.

JDJ

OSC01a

-1723982012

-944650159

OSC01b

Dendritic calcium spikes in layer 5 pyramidal neurons amplify and limit
transmission of ligand-gated dendritic current to soma.

2001

Long-lasting, dendritic, Ca(2+)-dependent action potentials (plateaus) were
investigated in layer 5 pyramidal neurons from rat neocortical slices
visualized by infrared-differential interference contrast microscopy to
understand the role of dendritic Ca(2+) spikes in the integration of synaptic
input. Focal glutamate iontophoresis on visualized dendrites caused soma
firing rate to increase linearly with iontophoretic current until dendritic
Ca(2+) responses caused a jump in firing rate. Increases in iontophoretic
current caused no further increase in somatic firing rate. This limitation of
firing rate resulted from the inability of increased glutamate to change
evoked plateau amplitude. Similar nonlinear patterns of soma firing were
evoked by focal iontophoresis on the distal apical, oblique, and basal
dendrites, whereas iontophoresis on the soma and proximal apical dendrite only
evoked a linear increase in firing rate as a function of iontophoretic current
without plateaus. Plateau amplitude recorded in the soma decreased as the site
of iontophoresis was moved farther from the soma, consistent with decremental
propagation of the plateau to the soma. Currents arriving at the soma summed
if plateaus were evoked on separate dendrites or if subthreshold responses
were evoked from sites on the same dendrite. If plateaus were evoked at two
sites on the same dendrite, only the proximal plateau was seen at the soma.
Just-subthreshold depolarizations at two sites on the same dendrite could sum
to evoke a plateau at the proximal site. We conclude that the plateaus prevent
current from ligand-gated channels distal to the plateau-generating region
from reaching the soma and directly influencing firing rate. The implications
of plateau properties for synaptic integration are discussed.

JDJ

OSC01b

-1633605921

1940208406

SBSC93

Calcium currents in acutely isolated human neocortical neurons.

1993

1. Ca2+ currents were investigated in neurons acutely isolated from adult human
temporal neocortex. The aim was to compare the basic characteristics of the
currents with those previously described in animals and to examine the effects
of dihydropyridine Ca2+ antagonists and antiepileptic drugs. The tissue,
obtained from patients undergoing temporal lobe surgery for medically
intractable epilepsy, was sliced, incubated in papain, and triturated. 2. Most
of the isolated neurons (34 of 36) were judged to be pyramidal cells by their
morphology. Whole-cell voltage-clamp recordings revealed two components of
Ca2+ current: 1) a low-threshold (T-type) current that was transient, small in
amplitude, and required hyperpolarization more negative than -70 mV for
removal of inactivation and 2) a high-threshold current that was slowly
inactivating and was available for activation from more positive potentials.
The characteristics of the Ca2+ currents were very similar to those in the
neocortical neurons of young rats, although the low-threshold current was less
prominent in the human cells. 3. Subcomponents of the high-threshold current
were identified by pharmacology. About 20% of the peak current was blocked by
omega-conotoxin GVIA (presumed N current) and 40-50% of the peak current was
blocked by micromolar concentrations of the dihydropyridine Ca2+ antagonists
nifedipine and nimodipine (presumed L current). In two neurons tested with a
range of nimodipine concentrations, the threshold for suppression of the
high-threshold current was approximately 10 nM. 4. The antiepileptic agents
ethosuximide, carbamazepine, and valproate did not affect the Ca2+ currents at
therapeutically relevant concentrations. Phenytoin marginally reduced the low-
and high-threshold Ca2+ currents at 8 microM (a concentration corresponding to
the upper therapeutic range). The results do not support the hypothesis that
inhibition of Ca2+ currents in neocortical pyramidal neurons is a major action
of these drugs.

JDJ

SBSC93

999521822

-866037043

SC95

Amplification of synaptic current by persistent sodium conductance in apical
dendrite of neocortical neurons.

1995

1. Evidence for amplification of synaptic current by voltage-gated channels in
dendrites of neocortical pyramidal neurons was demonstrated by examining the
effect of specific channel blocking agents on the current arriving at the soma
during iontophoresis of glutamate at a distal site on the apical dendrite. 2.
Dendritic noninactivating Na+ channels were implicated in this
voltage-dependent amplification of the transmitted current because it was
maintained for > 1 s and because tetrodotoxin (TTX) eliminated much of this
amplification. 3. Specific blockers of N-methyl-D-aspartate (NMDA) glutamate
receptors reduced the amplitude of the glutamate-evoked current at all
potentials and also reduced the non-TTX-sensitive component of
voltage-dependent augmentation. The effects of TTX were identical whether or
not NMDA channels were blocked. 4. We conclude that a persistent Na+
conductance exists in the apical dendrite of neocortical neurons. Together
with the NMDA conductance at the synaptic site it provides a mechanism for the
graded, voltage-dependent amplification of tonic, excitatory synaptic input.
This amplification results in much more effective transmission of tonic
excitatory current to the soma than would occur in a passive dendrite.

JDJ

SC95

-979866364

SS95

Amplification of EPSPs by axosomatic sodium channels in neocortical pyramidal
neurons.

1995

Simultaneous somatic and dendritic recordings were made from the same
neocortical layer V pyramidal neuron, and current injection via the dendritic
recording pipette was used to simulate the voltage change that occurs during
an EPSP. At the soma, these simulated EPSPs increased nonlinearly with the
amplitude of the dendritic current injection and with depolarization of the
membrane potential. Bath application of the sodium channel blocker TTX
decreased large (> 5 mV) EPSPs and also blocked amplification of EPSPs at
depolarized membrane potentials, whereas calcium channel blockers had little
effect. Local application of TTX to the soma and axon blocked EPSP
amplification, whereas dendritic application had little effect. Simultaneous
somatic and axonal recordings demonstrated that EPSP amplification was largest
in the axon. These results show that EPSPs are amplified by voltage-activated
sodium channels located close to the soma and in the axon.

JDJ

SS95

SSC90

High- and low-threshold calcium currents in neurons acutely isolated from rat
sensorimotor cortex.

1990

Neurons were isolated by papain treatment and trituration of the frontoparietal
cortex of 14 to 28-day-old rats. Whole cell voltage clamp revealed a slowly
inactivating high-threshold Ca2+ current, activated positive to -45 mV, and a
transient low-threshold Ca2+ current, activated positive to -65 mV. The
high-threshold current was more sensitive to block by Cd2+ and the
low-threshold current was more sensitive to block by Ni2+. Replacement of Ca2+
by Ba2+ increased the high-threshold current and reduced the low-threshold
current. The high-threshold current was enhanced by Bay K 8644 and reduced by
nimodipine and omega-conotoxin. The low-threshold current was also reduced by
nimodipine but was insensitive to Bay K 8644 and omega-conotoxin. The
properties of the currents were consistent with different underlying Ca2+
channel types.

Brief.

JDJ

SSC90

974817158

-806603121

SSSS97

Calcium action potentials restricted to distal apical dendrites of rat
neocortical pyramidal neurons.

1997

1. Simultaneous whole-cell voltage and Ca2+ fluorescence measurements were made
from the distal apical dendrites and the soma of thick tufted pyramidal
neurons in layer 5 of 4-week-old (P28-32) rat neocortex slices to investigate
whether activation of distal synaptic inputs can initiate regenerative
responses in dendrites. 2. Dual whole-cell voltage recordings from the distal
apical trunk and primary tuft branches (540-940 microns distal to the soma)
showed that distal synaptic stimulation (upper layer 2) evoking a subthreshold
depolarization at the soma could initiate regenerative potentials in distal
branches of the apical tuft which were either graded or all-or-none. These
regenerative potentials did not propagate actively to the soma and axon. 3.
Calcium fluorescence measurements along the apical dendrites indicated that
the regenerative potentials were associated with a transient increase in the
concentration of intracellular free calcium ([Ca2+]i) restricted to distal
dendrites. 4. Cadmium added to the bath solution blocked both the all-or-more
dendritic regenerative potentials and local dendritic [Ca2+]i transients
evoked by distal dendritic current injection. Thus, the regenerative
potentials in distal dendrites represent local Ca2+ action potentials. 5.
Initiation of distal Ca2+ action potentials by a synaptic stimulus required
coactivation of AMPA- and NMDA-type glutamate receptor channels. 6. It is
concluded that in neocortical layer 5 pyramidal neurons of P28-32 animals
glutamatergic synaptic inputs to the distal apical dendrites can be amplified
via local Ca2+ action potentials which do not reach threshold for axonal AP
initiation. As amplification of distal excitatory synaptic input is associated
with a localized increase in [Ca2+]i these Ca2+ action potentials could
control the synaptic efficacy of the distal cortico-cortical inputs to layer 5
pyramidal neurons.

JDJ

SSSS97

-847634651

-2140593619

TBGW03

Fast rhythmic bursting can be induced in layer 2/3 cortical neurons by
enhancing persistent Na+ conductance or by blocking BK channels

2003

Fast rhythmic bursting (or "chattering") is a firing pattern exhibited by
selected neocortical neurons in cats in vivo and in slices of adult ferret and
cat brain. Fast rhythmic bursting (FRB) has been recorded in certain
superficial and deep principal neurons and in aspiny presumed local circuit
neurons; it can be evoked by depolarizing currents or by sensory stimulation
and has been proposed to depend on a persistent g(Na) that causes spike
depolarizing afterpotentials. We constructed a multicompartment 11-conductance
model of a layer 2/3 pyramidal neuron, containing apical dendritic
calcium-mediated electrogenesis; the model can switch between rhythmic spiking
(RS) and FRB modes of firing, with various parameter changes. FRB in this
model is favored by enhancing persistent g(Na) and also by measures that
reduce [Ca(2+)](i) or that reduce the conductance of g(K(C)) (a fast voltage-
and Ca(2+)-dependent conductance). Axonal excitability plays a critical role
in generating fast bursts in the model. In vitro experiments in rat layer 2/3
neurons confirmed (as shown previously by others) that RS firing could be
switched to fast rhythmic bursting, either by buffering [Ca(2+)](i) or by
enhancing persistent g(Na). In addition, our experiments confirmed the model
prediction that reducing g(KC) (with iberiotoxin) would favor FRB. During the
bursts, fast prepotentials (spikelets) could occur that did not originate in
apical dendrites and that appear to derive from the axon. We suggest that
modulator-induced regulation of [Ca(2+)] dynamics or of BK channel
conductance, for example via protein kinase A, could play a role in
determining the firing pattern of neocortical neurons; specifically, such
modulation could play a role in regulating whether neurons respond to strong
stimulation with fast rhythmic bursts.

JDJ

TBGW03

-1892354029

-558364987

WS00

Site independence of EPSP time course is mediated by dendritic I(h) in
neocortical pyramidal neurons

2000

Neocortical layer 5 pyramidal neurons possess long apical dendrites that
receive a significant portion of the neurons excitatory synaptic input.
Passive neuronal models indicate that the time course of excitatory
postsynaptic potentials (EPSPs) generated in the apical dendrite will be
prolonged as they propagate toward the soma. EPSP propagation may, however, be
influenced by the recruitment of dendritic voltage-activated channels. Here we
investigate the properties and distribution of I(h) channels in the axon,
soma, and apical dendrites of neocortical layer 5 pyramidal neurons, and their
effect on EPSP time course. We find a linear increase (9 pA/100 microm) in the
density of dendritic I(h) channels with distance from soma. This nonuniform
distribution of I(h) channels generates site independence of EPSP time course,
such that the half-width at the soma of distally generated EPSPs (up to 435
microm from soma) was similar to somatically generated EPSPs. As a corollary,
a normalization of temporal summation of EPSPs was observed. The site
independence of somatic EPSP time course was found to collapse after
pharmacological blockade of I(h) channels, revealing pronounced temporal
summation of distally generated EPSPs, which could be further enhanced by
TTX-sensitive sodium channels. These data indicate that an increasing density
of apical dendritic I(h) channels mitigates the influence of cable filtering
on somatic EPSP time course and temporal summation in neocortical layer 5
pyramidal neurons.

JDJ

WS00

655797886

-781327707

ZC99

Intrinsic firing patterns and whisker-evoked synaptic responses of neurons in
the rat barrel cortex

1999

We have used whole cell recording in the anesthetized rat to study
whisker-evoked synaptic and spiking responses of single neurons in the barrel
cortex. On the basis of their intrinsic firing patterns, neurons could be
classified as either regular-spiking (RS) cells, intrinsically burst-spiking
(IB) cells, or fast-spiking (FS) cells. Some recordings responded to current
injection with a complex spike pattern characteristic of apical dendrites. All
cell types had high rates of spontaneous postsynaptic potentials, both
excitatory (EPSPs) and inhibitory (IPSPs). Some spontaneous EPSPs reached
threshold, and these typically elicited only single action potentials in RS
cells, bursts of action potentials in FS cells and IB cells, and a small, fast
spike or a complex spike in dendrites. Deflection of single whiskers evoked a
fast initial EPSP, a prolonged IPSP, and delayed EPSPs in all cell types. The
intrinsic firing pattern of cells predicted their short-latency whisker-evoked
spiking patterns. All cell types responded best to one or, occasionally, two
primary whiskers, but typically 6-15 surrounding whiskers also generated
significant synaptic responses. The initial EPSP had a relatively fixed
amplitude and latency, and its amplitude in response to first-order
surrounding whiskers was approximately 55% of that induced by the primary
whisker. Second- and third-order surrounding whiskers evoked responses of
approximately 27 and 12%, respectively. The latency of the initial EPSP was
shortest for the primary whiskers, longer for surrounding whiskers, and varied
with the neurons' depth below the pia. EPSP latency was shortest in the
granular layer, longer in supragranular layers, and longest in infragranular
layers. The receptive field size, defined as the total number of fast
EPSP-inducing whiskers, was independent of each cell's intrinsic firing type,
its subpial depth, or the whisker stimulus parameters. On average, receptive
fields included >10 whiskers. Our results show that single neurons
integrate rapid synaptic responses from a large proportion of the mystacial
vibrissae, and suggest that the whisker-evoked responses of barrel neurons are
a function of both synaptic inputs and intrinsic membrane properties.

JDJ

ZC99

39353653

-1387839592