GABAERGIC SYNAPTIC DIVERSITY AND ITS POSTSYNAPTIC EFFECTS: REGULATION OF NEURONAL EXCITABILITY BY CHANGES IN IPSC VARIANCE
Abstract number :
2.027
Submission category :
Year :
2002
Submission ID :
1509
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Ildiko Aradi, Vijayalakshmi Santhakumar, Kang Chen, Ivan Soltesz. Anatomy and Neurobiology, University of California, Irvine, Irvine, CA
RATIONALE: 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 IPSCs, even without alteration in the mean amplitude or kinetics of IPSC populations arriving at single cells, can significantly modify the effects of GABAergic inputs on neuronal excitability. Following this presentation the participants will be able to discuss the role of changes in variability in GABAergic synaptic inputs as a possible mechanism underlying inhibitory control of principal cells.
METHODS: 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 (Chen et al., Nat. Med. 2001; Aradi and Soltesz, J. Physiol. 2002).
RESULTS: The simulations showed that increased variance in the conductance or decay of IPSCs, even without changes in the mean, 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 conductance and mean decay time constant of the IPSCs, 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 could be entirely predicted from the non-linear actions of IPSCs on action potential generation.
CONCLUSIONS: These data show that the degree of heterogeneity of the GABAergic synaptic inputs to principal cells can modulate the efficacy of GABAergic inhibition. Therefore, modified variability of inhibitory inputs (e.g. after interneuron loss) may constitute a novel factor in the generation of seizures. The results have interesting implications for our understanding of the evolution of the diversity of interneurons in cortical and hippocampal circuits, as well as for the unraveling of novel forms of GABAergic plasticity that may take place in epilepsy.
[Supported by: NIH (NS35915) to I.S.]