Postsynaptic effects of GABAergic synaptic diversity: regulation of neuronal excitability by changes in IPSC variance.

Full Abstract

GABAergic synaptic inputs to principal cells are heterogeneous in terms of their anatomical, molecular and physiological properties. Whether diversity in GABAergic synaptic inputs affects the efficacy of GABAergic inhibition is not understood. Here we show that alterations in the heterogeneity of IPSC populations arriving at single cells can significantly modify the effects of GABAergic inputs on neuronal excitability. The effects of IPSC diversity were examined in a computational model that incorporated experimentally measured values for spontaneous IPSCs and CA1 pyramidal cell electrophysiological properties. The simulations showed that increased variance in the conductance or decay of IPSCs could potently modulate the firing rate of the postsynaptic cells. The actual direction of the IPSC variance-induced modulation in postsynaptic cell discharges depended on the mean IPSC conductance and mean decay time constant around which the variance was introduced, as well as on the degree of depolarization and firing of the postsynaptic cell. Further analysis of the underlying mechanisms determined that these effects of IPSC variance on neuronal excitability were entirely predicted from the non-linear actions of IPSCs on action potential generation. The variance effects on neuronal excitability could be strong enough to overcome even large changes in mean IPSC conductance, demonstrating that increased mean synaptic conductance (or increased mean IPSC or IPSP) alone does not necessarily imply a more effective inhibition, a finding which has important implications for epilepsy research. These data show that the degree of heterogeneity of the GABAergic synaptic inputs to principal cells can powerfully modulate the efficacy of GABAergic inhibition. The results indicate the functional importance of the diversity of interneurons in cortical and hippocampal circuits, and suggest that plastic changes in GABAergic synaptic diversity may modulate neuronal excitability under both normal and pathological conditions.

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Author information

Author/s: Aradi, Ildiko (I); Santhakumar, Vijayalakshmi (V); Chen, Kang (K); Soltesz, Ivan (I);

Affiliation: Department of Anatomy and Neurobiology, University of California Irvine, 92697-1280, USA.

Grants: NS35915 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, U.S. Gov't, P.H.S.

Journal: Neuropharmacology (Neuropharmacology), published in England. (Language: eng)

Reference: 2002-Sep; vol 43 (issue 4) : pp 511-22

Dates: Created 2002/10/07; Completed 2002/12/24; Revised 2007/11/14;

PMID: 12367598, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Cerebral Cortex - cytology; physiology
Excitatory Postsynaptic Potentials - physiology
Humans
Interneurons - physiology
Kinetics
Models, Neurological

Models, Neurological
Neuronal Plasticity - drug effects
Pyramidal Cells - drug effects
Receptors, GABA-A - physiology
Synapses - physiology
gamma-Aminobutyric Acid - physiology

Associated Chemicals: Receptors, GABA-A (0) ; gamma-Aminobutyric Acid (56-12-2)

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