GABA itself promotes the developmental switch of neuronal GABAergic responses from excitation to inhibition

Cell. 2001 May 18;105(4):521-32. doi: 10.1016/s0092-8674(01)00341-5.

Abstract

GABA is the main inhibitory neurotransmitter in the adult brain. Early in development, however, GABAergic synaptic transmission is excitatory and can exert widespread trophic effects. During the postnatal period, GABAergic responses undergo a switch from being excitatory to inhibitory. Here, we show that the switch is delayed by chronic blockade of GABA(A) receptors, and accelerated by increased GABA(A) receptor activation. In contrast, blockade of glutamatergic transmission or action potentials has no effect. Furthermore, GABAergic activity modulated the mRNA levels of KCC2, a K(+)-Cl(-) cotransporter whose expression correlates with the switch. Finally, we report that GABA can alter the properties of depolarization-induced Ca(2+) influx. Thus, GABA acts as a self-limiting trophic factor during neural development.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Chlorides / metabolism
  • Gene Expression Regulation, Developmental / physiology
  • Hippocampus / cytology*
  • Hippocampus / embryology*
  • Neural Inhibition / physiology*
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, GABA-A / physiology*
  • Signal Transduction / physiology
  • Symporters*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Carrier Proteins
  • Chlorides
  • RNA, Messenger
  • Receptors, GABA-A
  • Symporters
  • potassium-chloride symporters
  • gamma-Aminobutyric Acid
  • Potassium
  • Calcium