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GABAergic functions in the developing neuronal networks

Name
Roustem
Surname
Khazipov
Scientific organization
Kazan Federal University
Academic degree
PhD, MD
Position
Directeur de Recherche (INSERM U901 - Inmed), senior research fellow (OpenLab Neurobiology KFU), professor (Department of Human and Animal Physiology KFU)
Scientific discipline
Life Sciences & Medicine
Topic
GABAergic functions in the developing neuronal networks
Abstract
Не заполнено
Keywords
GABA, development, cerebral cortex, network activity, patch-clamp
Summary

During development, GABA, which is the main inhibitory neurotransmitter in cerebral cortex, exerts paradoxical excitatory actions on the immature neurons. Excitatory actions of GABA during development are due to the elevated intracellular chloride concentration and thus depolarizing direction of currents through GABA(A) ion channels. However, the roles of GABAergic mechanisms in the operation of immature neuronal networks remain poorly understood. Recent studies have provided important insights into the understanding of how GABA controls activity in the developing cortical networks. Firstly, using gramicidin perforated patch recordings from CA3 pyramidal cells we have shown that during generation of the recurrent network bursts in the neonatal rat hippocampal slices in vitro (so-called Giant Depolarizing Potentials), GABA transiently switches its action from depolarizing/excitatory to hyperpolarizing/inhibitory. These dynamic changes in the GABAergic actions on principal neurons enable GABA not only to initiate network bursts, but also to inhibit neuronal network at the peak of the network excitation. Moreover, using optogenetic approach in the mice expressing photoactivated channelrhodopsin in GABAergic interneurons, we have shown that in the neonatal cortex in vivo GABA reduces the frequency of glutamatergic postsynaptic currents and thus exerts mainly inhibitory actions in the developing cortical networks. These findings indicate that GABAergic functions are more complex than simplistic view on GABA as purely excitatory neurotransmitter despite of its depolarizing actions in the developing brain. The complexity in the actions of depolarizing GABA at the network level may be important not only during development but also in a number of pathological states including epilepsy, trauma and pain, where depolarizing shifts in the GABA actions may occur.