Temporal coding at the immature depolarizing GABAergic synapse

Valeeva Valeeva

doi:10.3389/fncel.2010.00017

Abstract

In the developing hippocampus, GABA exerts depolarizing and excitatory actions and contributes to the generation of neuronal network driven giant depolarizing potentials (GDPs). Here, we studied spike time coding at immature GABAergic synapses and its impact on synchronization of the neuronal network during GDPs in the neonatal (postnatal days P2–6) rat hippocampal slices. Using extracellular recordings, we found that the delays of action potentials (APs) evoked by synaptic activation of GABA(A) receptors are long (mean, 65 ms) and variable (within a time window of 10–200 ms). During patch-clamp recordings, depolarizing GABAergic responses were mainly subthreshold and their amplification by persistent sodium conductance was required to trigger APs. AP delays at GABAergic synapses shortened and their variability reduced with an increase in intracellular chloride concentration during whole-cell recordings. Negative shift of the GABA reversal potential (EGABA) with low concentrations of bumetanide, or potentiation of GABA(A) receptors with diazepam reduced GDPs amplitude, desynchronized neuronal firing during GDPs and slowed down GDPs propagation. Partial blockade of GABA(A) receptors with bicuculline increased neuronal synchronization and accelerated GDPs propagation. We propose that spike timing at depolarizing GABA synapses is determined by intracellular chloride concentration. At physiological levels of intracellular chloride GABAergic depolarization does not reach the action potential threshold and amplification of GABAergic responses by non-inactivating sodium conductance is required for postsynaptic AP initiation. Slow and variable excitation at GABAergic synapse determines the level of neuronal synchrony and the rate of GDPs propagation in the developing hippocampus.

Highlights

Gamma aminobutyric acid is the main inhibitory neurotransmitter in the adult brain
The main findings of the present study are the following: (i) delays of action potentials (APs) evoked by synaptic GABA in neonatal CA3 pyramidal cells are long and variable, and depend on intracellular chloride concentration; (ii) at physiological conditions, depolarization produced by GABA is typically more negative than the AP threshold (APthr), and activation of subthreshold voltage-gated INap is required to trigger APs; (iii) while depolarizing action of GABA is required for giant depolarizing potentials (GDPs) generation, slow and variable AP delays in GABAergic synapses reduce neuronal synchrony during generation of GDPs and slow down GDPs propagation
Excitatory actions of GABA in the immature neurons have been well documented in various brain structures (Ben Ari et al, 2007), the temporal AP coding aspect of GABAergic excitation until present study has not been analyzed

Summary

Introduction

Synchronous inhibition by hyperpolarization and shunt provided by GABAergic interneurons is instrumental for the generation of various network activity patterns in the adult brain (Freund and Buzsaki, 1996). Depolarizing GABA is involved in the generation of primitive pattern of neuronal network activity in the immature hippocampus – so called GDPs (Ben-Ari et al, 1989; Khazipov et al, 2004; Dzhala et al, 2005; Sipila et al, 2005). Excitation to pyramidal cells and interneurons during GDPs is brought by synergistic excitatory actions of GABA and glutamate (Menendez de la et al, 1996; Khazipov et al, 1997; Leinekugel et al, 1997; De la Prida et al, 1998; Bolea et al, 1999; Lamsa et al, 2000). Factors determining spatio-temporal characteristics of GPDs and spike timing during GDPs are not completely understood

Methods

Results

Conclusion