gamma-Aminobutyric acid hyperpolarizes rat hippocampal pyramidal cells through a calcium-dependent potassium conductance.

1. Starting with published data derived mainly from hippocampal slice preparations, we have used computer-modeling techniques to study hippocampal pyramidal cells (HPCs). 2. The dendrites of the HPC apparently have a short electrotonic length. Calcium spikes are apparently generated by a voltage-dependent mechanism whose kinetics are slow in comparison with those generating sodium spikes of the soma. Inward calcium currents are assumed to trigger a long-lasting potassium conductance. This slow calcium-potassium system, which in our model is located predominantly on the dendrites, provides a heuristic model to describe the mechanism for a) the after-depolarization following an HPC soma (sodium) spike, b) the long afterhyperpolarization following repetitive firing, c) bursts of spikes that sometimes occur after orthodromic or antidromic stimulation, and d) the buildup of the "depolarizing shift" during the strong synaptic input presumed to occur during seizures. 3. Fast prepotentials or d-spikes are shown to arise most probably from dendritic "hot spots" of sodium-regenerative membrane. The limited amplitude and short duration of these prepotentials imply that the hot spots are located on small dendrites. 4. Dendritic electroresponsiveness, first postulated for the HPC by Spencer and Kandel (52), is analyzed quantitatively here and is shown to provide rich integrative possibilities for this cell. Our model suggests that, for these nerve cells, alterations in specific membrane properties, particularly calcium electroresponsiveness, can lead to bursting behavior that resembles epileptogenic neuronal responses.

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Ammonia does not selectively block IPSPs in rat hippocampal pyramidal cells

Journal of Neurophysiology ◽

10.1152/jn.1983.49.6.1381 ◽

1983 ◽

Vol 49 (6) ◽

pp. 1381-1391 ◽

Cited By ~ 43

Author(s):

B. E. Alger ◽

R. A. Nicoll

Keyword(s):

Reversal Potential ◽

Pyramidal Cells ◽

Gamma Aminobutyric Acid ◽

Postsynaptic Potentials ◽

Calcium Dependent ◽

Nonspecific Effects ◽

Chloride Pump ◽

High Concentrations ◽

Conductance Increase ◽

Potassium Response

Intracellular recordings from CA1 pyramidal cells in the rat hippocampal slice preparation have been used to study the action of ammonia on inhibitory postsynaptic potentials (IPSPs). Concentrations of ammonia less than 2 mM had little effect on IPSPs or the action of iontophoretically applied gamma-aminobutyric acid (GABA). This concentration has been reported to be fully effective in blocking hyperpolarizing IPSPs in spinal cord and neocortex. Concentrations above 2 mM did cause a depolarizing shift in the IPSP and GABA reversal potentials, but this effect was accompanied by several generalized effects. The conductance increase during the IPSP but not during the GABA response was depressed, indicating that ammonia has a presynaptic depressant effect on the IPSP. Ammonia also depressed excitatory postsynaptic potentials (EPSPs), presynaptic fiber potentials, and pyramidal cell population spikes. In addition, the calcium-dependent potassium response elicited by depolarizing current pulses was depressed. This depression was due, in part, to a depolarizing shift in the reversal potential for this response. Responses recorded with potassium-sensitive microelectrodes indicate that ammonia releases potassium into the extracellular space. The possibility is discussed that the shifts in IPSP reversal potential seen with high concentrations of ammonia are a consequence of generalized nonspecific effects. We conclude that the relative insensitivity of hippocampal IPSPs to blockade by ammonia suggests that a mechanism fundamentally unlike an ammonia-sensitive chloride pump must maintain the hippocampal IPSP gradient.

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Neuroleptics decrease calcium-activated potassium conductance in hippocampal pyramidal cells

Brain Research ◽

10.1016/0006-8993(87)91231-5 ◽

1987 ◽

Vol 407 (1) ◽

pp. 159-162 ◽

Cited By ~ 28

Author(s):

Timothy G. Dinan ◽

Vincenzo Crunelli ◽

John S. Kelly

Keyword(s):

Potassium Conductance ◽

Pyramidal Cells ◽

Calcium Activated Potassium Conductance ◽

Hippocampal Pyramidal Cells

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Foxg1 Upregulation Enhances Neocortical Activity

Cerebral Cortex ◽

10.1093/cercor/bhaa107 ◽

2020 ◽

Vol 30 (9) ◽

pp. 5147-5165

Author(s):

Wendalina Tigani ◽

Moira Pinzan Rossi ◽

Osvaldo Artimagnella ◽

Manuela Santo ◽

Rossana Rauti ◽

...

Keyword(s):

Primary Cultures ◽

Cell Activity ◽

Pyramidal Cells ◽

Copy Number Variations ◽

Aminobutyric Acid ◽

Gamma Aminobutyric Acid ◽

Transcription Factor Gene ◽

Neocortical Neurons ◽

Genes Encoding ◽

Neuronal Physiology

Abstract Foxg1 is an ancient transcription factor gene orchestrating a number of neurodevelopmental processes taking place in the rostral brain. In this study, we investigated its impact on neocortical activity. We found that mice overexpressing Foxg1 in neocortical pyramidal cells displayed an electroencephalography (EEG) with increased spike frequency and were more prone to kainic acid (KA)-induced seizures. Consistently, primary cultures of neocortical neurons gain-of-function for Foxg1 were hyperactive and hypersynchronized. That reflected an unbalanced expression of key genes encoding for ion channels, gamma aminobutyric acid and glutamate receptors, and was likely exacerbated by a pronounced interneuron depletion. We also detected a transient Foxg1 upregulation ignited in turn by neuronal activity and mediated by immediate early genes. Based on this, we propose that even small changes of Foxg1 levels may result in a profound impact on pyramidal cell activity, an issue relevant to neuronal physiology and neurological aberrancies associated to FOXG1 copy number variations.

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Classical conditioning reduces amplitude and duration of calcium-dependent afterhyperpolarization in rabbit hippocampal pyramidal cells

Journal of Neurophysiology ◽

10.1152/jn.1989.61.5.971 ◽

1989 ◽

Vol 61 (5) ◽

pp. 971-981 ◽

Cited By ~ 161

Author(s):

D. A. Coulter ◽

J. J. Lo Turco ◽

M. Kubota ◽

J. F. Disterhoft ◽

J. W. Moore ◽

...

Keyword(s):

Hippocampal Slices ◽

Pyramidal Cells ◽

Channel Blockers ◽

Calcium Spikes ◽

Calcium Dependent ◽

Current Threshold ◽

The Difference ◽

And Control ◽

Hippocampal Pyramidal Cells ◽

In Cells

1. The afterhyperpolarization (AHP) that follows action potentials was studied in CA1 hippocampal pyramidal cells from classically conditioned and control rabbits. Measurements of the AHP were obtained with intracellular recordings from CA1 cells within hippocampal slices. 2. The AHP of rabbit CA1 pyramidal cells was found to be accompanied by a conductance increase. The AHP was reduced by bath applications of the calcium channel blockers, cadmium and cobalt, by bath application of the cholinergic agonist, carbamylcholine chloride, and intracellular injection of the calcium chelator, ethylene glycol-bis(B-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). 3. The AHP was markedly reduced in cells from rabbits that were well-trained with the nictitating membrane conditioning procedure, as compared with cells from pseudoconditioned or naive control animals. The difference in AHP amplitudes between conditioned and control groups increased as the number of spikes elicited by the stimulation pulse increased from one to four. Both the duration (measured as the time constant of AHP decay) and amplitude of the AHP were reduced in cells from conditioned animals. 4. The reduced AHP in cells from conditioned animals remained reduced in a medium that contained 0.5 microM tetrodotoxin (TTX) and 5.0 mM tetraethylammonium chloride (TEA); the AHP following calcium spikes was measured under these conditions. Since this medium eliminated synaptic transmission elicited by Schaeffer collateral stimulation, the AHP reduction in pyramidal cells from conditioned animals was not due to a modification in synaptic properties. There were no significant differences in the mean voltage thresholds, amplitudes, or durations of calcium spikes between cells from animals in the three groups. Thus the AHP reduction appears to be due to a modification of a Ca2+ -dependent K+ conductance and was not due to a secondary effect of reductions in calcium conductances underlying the spike. 5. In medium containing TTX and TEA, the amount of injected current required to elicit a calcium spike (current threshold) was significantly greater in cells from conditioned animals than in cells from control animals. This increase in current threshold persisted in 4-aminopyridine (4-AP)-containing medium and so cannot be attributed entirely to conditioning-specific increases in the A-current. 6. The conditioning-specific AHP reduction resulted in increased excitability in cells from conditioned animals versus pseudoconditioned control animals. Cells from conditioned animals fired more spikes to trains of 100-ms depolarizing current pulses than did cells from controls.

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