Article

Molecular Neurobiology

, Volume 43, Issue 2, pp 97-106

First online:

The Depolarizing Action of GABA Controls Early Network Activity in the Developing Hippocampus

  • Enrico CherubiniAffiliated withNeurobiology Sector and IIT Unit, International School for Advanced Studies (SISSA) Email author 
  • , Marilena GriguoliAffiliated withNeurobiology Sector and IIT Unit, International School for Advanced Studies (SISSA)
  • , Victoria SafiulinaAffiliated withNeurobiology Sector and IIT Unit, International School for Advanced Studies (SISSA)
  • , Laura LagostenaAffiliated withNeurobiology Sector and IIT Unit, International School for Advanced Studies (SISSA)

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Abstract

Early in postnatal life γ-aminobutyric acid (GABA), the primary inhibitory transmitter in adults, excites targeted neurons by an outwardly directed flux of chloride which results from the unbalance between the cation–chloride cotransporters NKCC1 and KCC2, involved in chloride uptake and extrusion, respectively. This effect contributes to generate synchronized network activity or giant depolarizing potentials (GDPs) in the developing hippocampus. Here, we review some recent data concerning the mechanisms by which GDPs are generated and their functional role in enhancing synaptic efficacy at poorly developed GABAergic and glutamatergic synapses. In adulthood, reshaping neuronal circuits due to changes in chloride homeostasis and to the shift of GABA from hyperpolarizing to depolarizing, has been implicated in several neurological disorders, including epilepsy. Evidence has been recently provided that in chronically nerve growth factor-deprived mice expressing a progressive age-dependent neurodegenerative pathology resembling that observed in patients with Alzheimer’s disease, the reduced expression of mRNA encoding for the Kcc2 gene and the depolarizing action of GABA lead to the reorganization of the neuronal hippocampal network. This may represent a novel mechanism by which GABAergic signaling counterbalances the loss of synaptic activity in neurodegenerative diseases.

Keywords

Depolarizing action of GABA Development Cation–chloride cotransporters Synaptic efficacy Correlated network activity GDPs NGF Neurodegeneration