Estimating the Time Course of the Excitatory Synaptic Conductance in Neocortical Pyramidal Cells Using a Novel Voltage Jump Method

The temporal precision of converting excitatory postsynaptic potentials (EPSPs) into spikes at pyramidal cells is critical for the coding of information in the cortex. Several in vitro studies have shown that voltage-dependent conductances in pyramidal cells can prolong the EPSP time course resulting in an imprecise EPSP-spike coupling. We have used dynamic-clamp techniques to mimic the in vivo background synaptic conductance in cortical slices and investigated how the ongoing synaptic activity may affect the EPSP time course near threshold and the EPSP spike coupling. We report here that background synaptic conductance dramatically diminished the depolarization related prolongation of the EPSPs in pyramidal cells and improved the precision of spike timing. Furthermore, we found that background synaptic conductance can affect the interaction among action potentials in a spike train. Thus the level of ongoing synaptic activity in the cortex may regulate the capacity of pyramidal cells to process temporal information.

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GABAA-Mediated IPSCs in Piriform Cortex Have Fast and Slow Components With Different Properties and Locations on Pyramidal Cells

Journal of Neurophysiology ◽

10.1152/jn.1997.78.5.2531 ◽

1997 ◽

Vol 78 (5) ◽

pp. 2531-2545 ◽

Cited By ~ 49

Author(s):

A. Kapur ◽

R. A. Pearce ◽

W. W. Lytton ◽

L. B. Haberly

Keyword(s):

Time Course ◽

Feedback Inhibition ◽

Slow Component ◽

Piriform Cortex ◽

Pyramidal Cells ◽

Long Term Potentiation ◽

Companion Paper ◽

Protective Role ◽

Functional Roles ◽

Term Potentiation

Kapur, A., R. A. Pearce, W. W. Lytton, and L. B. Haberly.GABAA-mediated IPSCs in piriform cortex have fast and slow components with different properties and locations on pyramidal cells. J. Neurophysiol. 78: 2531–2545, 1997. A recent study in piriform (olfactory) cortex provided evidence that, as in hippocampus and neocortex, γ-aminobutyric acid-A (GABAA)-mediated inhibition is generated in dendrites of pyramidal cells, not just in the somatic region as previously believed. This study examines selected properties of GABAA inhibitory postsynaptic currents (IPSCs) in dendritic and somatic regions that could provide insight into their functional roles. Pharmacologically isolated GABAA-mediated IPSCs were studied by whole cell patch recording in slices. To compare properties of IPSCs in distal dendritic and somatic regions, local stimulation was carried out with tungsten microelectrodes, and spatially restricted blockade of GABAA-mediated inhibition was achieved by pressure-ejection of bicuculline from micropipettes. The results revealed that largely independent circuits generate GABAA inhibition in distal apical dendritic and somatic regions. With such independence, a selective decrease in dendritic-region inhibition could enhance integrative or plastic processes in dendrites while allowing feedback inhibition in the somatic region to restrain system excitability. This could allow modulatory fiber systems from the basal forebrain or brain stem, for example, to change the functional state of the cortex by altering the excitability of interneurons that mediate dendritic inhibition without increasing the propensity for regenerative bursting in this highly epileptogenic system. As in hippocampus, GABAA-mediated IPSCs were found to have fast and slow components with time constants of decay on the order of 10 and 40 ms, respectively, at 29°C. Modeling analysis supported physiological evidence that the slow time constant represents a true IPSC component rather than an artifactual slowing of the fast component from voltage clamp of a dendritic current. The results indicated that, whereas both dendritic and somatic-region IPSCs have both fast and slow GABAA components, there is a greater proportion of the slow component in dendrites. In a companion paper, the hypothesis is explored that the resulting slower time course of the dendritic IPSC increases its capacity to regulate the N-methyl-d-aspartate component of EPSPs. Finally, evidence is presented that the slow GABAA-mediated IPSC component is regulated by presynaptic GABAB inhibition whereas the fast is not. Based on the requirement for presynaptic GABAB-mediated block of inhibition for expression of long-term potentiation, this finding is consistent with participation of the slow GABAA component in regulation of synaptic plasticity. The lack of susceptibility of the fast GABAA component to the long-lasting, activity-induced suppression mediated by presynaptic GABAB receptors is consistent with a protective role for this process in preventing seizure activity.

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Dynamic Change in Cells Expressing IL-1β in Rat Hippocampus after Status Epilepticus

Japanese Clinical Medicine ◽

10.4137/jcm.s13738 ◽

2014 ◽

Vol 5 ◽

pp. JCM.S13738 ◽

Cited By ~ 1

Author(s):

Satoru Sakuma ◽

Daisuke Tokuhara ◽

Hiroshi Otsubo ◽

Tsunekazu Yamano ◽

Haruo Shintaku

Keyword(s):

Status Epilepticus ◽

Cellular Localization ◽

Wistar Rats ◽

Time Course ◽

Dynamic Change ◽

Chronic Phase ◽

Pyramidal Cells ◽

Reactive Astrocytes ◽

Time Courses ◽

Ca3 Pyramidal Cells

Background The time course of cytokine dynamics after seizure remains controversial. Here we evaluated the changes in the levels and sites of interleukin (IL)-1β expression over time in the hippocampus after seizure. Methods Status epilepticus (SE) was induced in adult Wistar rats by means of intraperitoneal injection of kainic acid (KA). Subsequently, the time courses of cellular localization and IL-1β concentration in the hippocampus were evaluated by means of immunohistochemical and quantitative assays. Results On day 1 after SE, CA3 pyramidal cells showed degeneration and increased IL-1β expression. In the chronic phase (>7 days after SE), glial fibrillary acidic protein (GFAP)–-positive reactive astrocytes–-appeared in CA1 and became IL-1β immunoreactive. Their IL-1β immunoreactivity increased in proportion to the progressive hypertrophy of astrocytes that led to gliosis. Quantitative analysis showed that hippocampal IL-1β concentration progressively increased during the acute and chronic phases. Conclusion IL-1β affects the hippocampus after SE. In the acute phase, the main cells expressing IL-1β were CA3 pyramidal cells. In the chronic phase, the main cells expressing IL-1β were reactive astrocytes in CA1.

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Activity-induced elevations of intracellular calcium concentration in pyramidal and nonpyramidal cells of the CA3 region of rat hippocampal slice cultures

Journal of Neurophysiology ◽

10.1152/jn.1992.68.3.961 ◽

1992 ◽

Vol 68 (3) ◽

pp. 961-963 ◽

Cited By ~ 20

Author(s):

T. Knopfel ◽

B. H. Gahwiler

Keyword(s):

Intracellular Calcium ◽

Time Course ◽

Calcium Concentration ◽

Potassium Conductance ◽

Pyramidal Cells ◽

Calcium Transients ◽

Intracellular Calcium Concentration ◽

Calcium Signal ◽

Cell Somata ◽

Ca3 Region

1. Depolarization-induced elevations of intracellular calcium concentration ([Ca2+]i) were examined in slice-cultured hippocampal pyramidal and nonpyramidal cells of the CA3 region by combined intracellular and multisite fura-2 recording techniques. 2. In pyramidal cells, spiking activity induced by depolarizing current pulses (200–800 ms) induced transient elevations of somatic as well as of proximal dendritic [Ca2+]i. The calcium signals from the proximal dendrites were larger in amplitude and decayed much faster than those from the soma. Depolarization of presumed interneurons induced comparable somatic and dendritic calcium transients, which decayed faster than those observed in pyramidal cell somata. 3. The calcium transients of pyramidal cells, but not those of nonpyramidal cells, were associated with a slow afterhyperpolarization (sAHP), whose time course was correlated with that of the somatic calcium signal. We conclude that the lack of a sAHP in non-pyramidal cells cannot be explained by the absence of an efficient rise in [Ca2+]i but rather by the absence of the potassium conductance underlying the sAHP in pyramidal cells.

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Estimation of Synaptic Activity during Neuronal Oscillations

Mathematics ◽

10.3390/math8122153 ◽

2020 ◽

Vol 8 (12) ◽

pp. 2153

Author(s):

Catalina Vich ◽

Rafel Prohens ◽

Antonio E. Teruel ◽

Antoni Guillamon

Keyword(s):

Time Course ◽

Mathematical Proof ◽

Brain Connectivity ◽

Synaptic Activity ◽

Synaptic Conductance ◽

Period Function ◽

Voltage Trace ◽

Local Functional ◽

Time Trace ◽

Synaptic Conductances

In the study of brain connectivity, an accessible and convenient way to unveil local functional structures is to infer the time trace of synaptic conductances received by a neuron by using exclusively information about its membrane potential (or voltage). Mathematically speaking, it constitutes a challenging inverse problem: it consists in inferring time-dependent parameters (synaptic conductances) departing from the solutions of a dynamical system that models the neuron’s membrane voltage. Several solutions have been proposed to perform these estimations when the neuron fluctuates mildly within the subthreshold regime, but very few methods exist for the spiking regime as large amplitude oscillations (revealing the activation of complex nonlinear dynamics) hinder the adaptability of subthreshold-based computational strategies (mostly linear). In a previous work, we presented a mathematical proof-of-concept that exploits the analytical knowledge of the period function of the model. Inspired by the relevance of the period function, in this paper we generalize it by providing a computational strategy that can potentially adapt to a variety of models as well as to experimental data. We base our proposal on the frequency versus synaptic conductance curve (f−gsyn), derived from an analytical study of a base model, to infer the actual synaptic conductance from the interspike intervals of the recorded voltage trace. Our results show that, when the conductances do not change abruptly on a time-scale smaller than the mean interspike interval, the time course of the synaptic conductances is well estimated. When no base model can be cast to the data, our strategy can be applied provided that a suitable f−gsyn table can be experimentally constructed. Altogether, this work opens new avenues to unveil local brain connectivity in spiking (nonlinear) regimes.

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Evidence for Endogenous Excitatory Amino Acids as Mediators in DSI of GABAAergic Transmission in Hippocampal CA1

Journal of Neurophysiology ◽

10.1152/jn.1999.82.5.2556 ◽

1999 ◽

Vol 82 (5) ◽

pp. 2556-2564 ◽

Cited By ~ 18

Author(s):

Wade Morishita ◽

Bradley E. Alger

Keyword(s):

Amino Acids ◽

Time Course ◽

Metabotropic Glutamate Receptor ◽

Excitatory Amino Acid ◽

Pyramidal Cells ◽

Kainate Receptors ◽

Sulfinic Acid ◽

Homocysteic Acid ◽

Group I ◽

Hippocampal Ca1

Depolarization-induced suppression of inhibition (DSI) is a process whereby brief ∼1-s depolarization to the postsynaptic membrane of hippocampal CA1 pyramidal cells results in a transient suppression of GABAAergic synaptic transmission. DSI is triggered by a postsynaptic rise in [Ca2+]in and yet is expressed presynaptically, which implies that a retrograde signal is involved. Recent evidence based on synthetic metabotropic glutamate receptor (mGluR) agonists and antagonists suggested that group I mGluRs take part in the expression of DSI and raised the possibility that glutamate or a glutamate-like substance is the retrograde messenger in hippocampal CA1. This hypothesis was tested, and it was found that the endogenous amino acidsl-glutamate (l-Glu) and l-cysteine sulfinic acid (l-CSA) suppressed GABAA-receptor–mediated inhibitory postsynaptic currents (IPSCs) and occluded DSI, whereas l-homocysteic acid (l-HCA) and l-homocysteine sulfinic acid (l-HCSA) did not. Activation of metabotropic kainate receptors with kainic acid (KA) reduced IPSCs; however, DSI was not occluded. When iontophoretically applied, both l-Glu andl-CSA produced a transient IPSC suppression similar in magnitude and time course to that observed during DSI. Both DSI and the actions of the amino acids were antagonized by (S)-α-methyl-4-carboxyphenylglycine ([S]-MCPG), indicating that the effects of the endogenous agonists were produced through activation of mGluRs. Blocking excitatory amino acid transport significantly increased DSI and the suppression produced by l-Glu orl-CSA without affecting the time constant of recovery from the suppression. Similar to DSI, IPSC suppression by l-Glu or l-CSA was blocked by N-ethylmaleimide (NEM). Moreover, paired-pulse depression (PPD), which is unaltered during DSI, is also not significantly affected by the amino acids. Taken together, these results support the glutamate hypothesis of DSI and argue that l-Glu or l-CSA are potential retrograde messengers in CA1.

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Tone-Evoked Excitatory and Inhibitory Synaptic Conductances of Primary Auditory Cortex Neurons

Journal of Neurophysiology ◽

10.1152/jn.01020.2003 ◽

2004 ◽

Vol 92 (1) ◽

pp. 630-643 ◽

Cited By ~ 175

Author(s):

Andrew Y. Y. Tan ◽

Li I. Zhang ◽

Michael M. Merzenich ◽

Christoph E. Schreiner

Keyword(s):

Auditory Cortex ◽

Time Course ◽

Frequency Tuning ◽

Primary Auditory Cortex ◽

Cell Voltage ◽

Synaptic Conductance ◽

Synaptic Excitation ◽

Tone Intensity ◽

Synaptic Conductances

In primary auditory cortex (AI) neurons, tones typically evoke a brief depolarization, which can lead to spiking, followed by a long-lasting hyperpolarization. The extent to which the hyperpolarization is due to synaptic inhibition has remained unclear. Here we report in vivo whole cell voltage-clamp measurements of tone-evoked excitatory and inhibitory synaptic conductances of AI neurons of the pentobarbital-anesthetized rat. Tones evoke an increase of excitatory synaptic conductance, followed by an increase of inhibitory synaptic conductance. The synaptic conductances can account for the gross time course of the typical membrane potential response. Synaptic excitation and inhibition have the same frequency tuning. As tone intensity increases, the amplitudes of synaptic excitation and inhibition increase, and the latency of synaptic excitation decreases. Our data indicate that the interaction of synaptic excitation and inhibition shapes the time course and frequency tuning of the spike responses of AI neurons.

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Probability of Transmitter Release at Neocortical Synapses at Different Temperatures

Journal of Neurophysiology ◽

10.1152/jn.01166.2003 ◽

2004 ◽

Vol 92 (1) ◽

pp. 212-220 ◽

Cited By ~ 60

Author(s):

Maxim Volgushev ◽

Igor Kudryashov ◽

Marina Chistiakova ◽

Mikhail Mukovski ◽

Johannes Niesmann ◽

...

Keyword(s):

Visual Cortex ◽

Nmda Receptor ◽

Transmitter Release ◽

Room Temperature ◽

Time Course ◽

Dynamic Properties ◽

Variable Temperature ◽

Pyramidal Cells ◽

Mk 801 ◽

Release Probability

The probability of transmitter release at synaptic terminals is one of the key characteristics of communication between nerve cells because it determines both the strength and dynamic properties of synaptic connections. To assess the distribution of the release probabilities at excitatory synapses on supragranular pyramidal cells in rat visual cortex, we have used the MK-801, a blocker of the open N-methyl-d-aspartate (NMDA) receptor-gated channels. With this method, the release probability can be calculated from the time course of the blockade of NMDA-receptor mediated postsynaptic currents in the presence of MK-801. At temperatures >32°C, the distribution of release probabilities covered the range from 0.05 to 0.43 [mean: 0.171 ± 0.012 (SE), n = 65], being skewed toward low values. When estimated at room temperature (22–25°C), the release probabilities were significantly lower (mean: 0.123 ± 0.009, n = 54), and almost the whole distribution was restricted to values <0.2. Furthermore, warming from room temperature to >32°C led to a pronounced overshooting increase of the release probability. Taken together, the results of the present study show that release probabilities at synapses formed onto layer 2/3 pyramidal cells in the visual cortex vary significantly, but values >0.3 are rare and the results obtained either at room or variable temperature differ significantly from those made under conditions of constant temperature in the physiological range.

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Patterned Activity in Stratum Lacunosum Moleculare Inhibits CA1 Pyramidal Neuron Firing

Journal of Neurophysiology ◽

10.1152/jn.1999.82.6.3213 ◽

1999 ◽

Vol 82 (6) ◽

pp. 3213-3222 ◽

Cited By ~ 46

Author(s):

Hannah Dvorak-Carbone ◽

Erin M. Schuman

Keyword(s):

Time Course ◽

Pyramidal Cells ◽

Stratum Radiatum ◽

High Frequency Stimulation ◽

Dependent Manner ◽

Ca1 Pyramidal Cells ◽

Frequency Stimulation ◽

Primary Output ◽

Ca1 Pyramidal Neuron ◽

Stratum Lacunosum Moleculare

CA1 pyramidal cells are the primary output neurons of the hippocampus, carrying information about the result of hippocampal network processing to the subiculum and entorhinal cortex (EC) and thence out to the rest of the brain. The primary excitatory drive to the CA1 pyramidal cells comes via the Schaffer collateral (SC) projection from area CA3. There is also a direct projection from EC to stratum lacunosum-moleculare (SLM) of CA1, an input well positioned to modulate information flow through the hippocampus. High-frequency stimulation in SLM evokes an inhibition sufficiently strong to prevent CA1 pyramidal cells from spiking in response to SC input, a phenomenon we refer to as spike-blocking. We characterized the spike-blocking efficacy of burst stimulation (10 stimuli at 100 Hz) in SLM and found that it is greatest at ∼300–600 ms after the burst, consistent with the time course of the slow GABABsignaling pathway. Spike-blocking efficacy increases in potency with the number of SLM stimuli in a burst, but also decreases with repeated presentations of SLM bursts. Spike-blocking was eliminated in the presence of GABABantagonists. We have identified a candidate population of interneurons in SLM and distal stratum radiatum (SR) that may mediate this spike-blocking effect. We conclude that the output of CA1 pyramidal cells, and hence the hippocampus, is modulated in an input pattern-dependent manner by activation of the direct pathway from EC.

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Dendrosomatic Voltage and Charge Transfer in Rat Neocortical Pyramidal Cells In Vitro

Journal of Neurophysiology ◽

10.1152/jn.2000.84.3.1445 ◽

2000 ◽

Vol 84 (3) ◽

pp. 1445-1452 ◽

Cited By ~ 9

Author(s):

Daniel Ulrich ◽

Christian Stricker

Keyword(s):

Membrane Potential ◽

Time Course ◽

Cutoff Frequency ◽

Pyramidal Cells ◽

Apical Dendrite ◽

Resting Membrane Potential ◽

Excitatory Postsynaptic Potential ◽

Transfer Characteristics ◽

Layer V

Most excitatory synapses on neocortical pyramidal cells are located on dendrites, which are endowed with a variety of active conductances. The main origin for action potentials is thought to be at the initial segment of the axon, although local regenerative activity can be initiated in the dendrites. The transfer characteristics of synaptic voltage and charge along the dendrite to the soma remains largely unknown, although this is an essential determinant of neural input-output transformations. Here we perform dual whole-cell recordings from layer V pyramidal cells in slices from somatosensory cortex of juvenile rats. Steady-state and sinusoidal current injections are applied to characterize the voltage transfer characteristics of the apical dendrite under resting conditions. Furthermore, dendrosomatic charge and voltage transfer are determined by mimicking synapses via dynamic current-clamping. We find that around rest, the dendrite behaves like a linear cable. The cutoff frequency for somatopetal current transfer is around 4 Hz, i.e., synaptic inputs are heavily low-pass filtered. In agreement with linearity, transfer resistances are reciprocal in opposite directions, and the centroids of the synaptic time course are on the order of the membrane time constant. Transfer of excitatory postsynaptic potential (EPSP) charge, but not peak amplitude, is positively correlated with membrane potential. We conclude that the integrative properties of dendrites in infragranular neocortical pyramidal cells appear to be linear near resting membrane potential. However, at polarized potentials charge transferred is voltage-dependent with a loss of charge at hyperpolarized and a gain of charge at depolarized potentials.

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