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GABA-activated Single-channel and Tonic Currents in Rat Brain Slices
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GAT-1 acts to limit a tonic GABA(A) current in rat CA3 pyramidal neurons at birth

Sampsa T Sipilä1, Juha Voipio, Kai Kaila

  • 1Department of Biological and Environmental Sciences, University of Helsinki, FIN-00014 Helsinki, Finland. Sampsa.Sipila@Helsinki.Fi

The European Journal of Neuroscience
|February 15, 2007
PubMed

Insights

Tonic GABA(A) receptor currents are present in early postnatal hippocampal neurons. GABA transporter-1 (GAT-1) activity influences these currents, suggesting a role in controlling neuronal excitability before synapses fully develop.

Area of Science:

  • Neuroscience
  • Developmental Neuroscience
  • Synaptic Plasticity

Background:

  • Tonic activation of GABA(A) receptors occurs before functional synapse development in cortical structures.
  • The source of tonic GABA currents in early development is not fully understood.
  • GABA uptake mechanisms may play a role in regulating early neuronal activity.

Purpose of the Study:

  • Investigate the role of GABA uptake in tonic GABA(A)-mediated currents (I(GABA-A)) in early postnatal hippocampal pyramidal neurons.
  • Determine if GABA transporter-1 (GAT-1) influences tonic I(GABA-A) in neonatal rat CA3 pyramidal neurons.
  • Examine the impact of GAT-1 blockade on GABA transients during giant depolarizing potentials.

Main Methods:

  • Electrophysiological recordings in rat CA3 pyramidal neurons at postnatal day 0.
  • Application of the GAT-1 specific blocker NO-711.
  • Assessment of tonic I(GABA-A) and GABA transients.
  • Experiments conducted in the presence of tetrodotoxin to evaluate action-potential independence.

Main Results:

  • The tonic I(GABA-A) in neonatal CA3 pyramidal neurons was enhanced by the GAT-1 blocker NO-711.
  • NO-711 prolonged the duration of GABA transients during giant depolarizing potentials.
  • The endogenous tonic I(GABA-A) was largely independent of action-potential activity.
  • Zolpidem increased tonic I(GABA-A), suggesting involvement of GABA(A) receptors with gamma2 and alpha1-alpha3 subunits.

Conclusions:

  • GABA transporter-1 (GAT-1) plays a significant role in controlling the excitability of immature hippocampal neurons and networks.
  • Inefficient GABA uptake is not the sole explanation for tonic currents; GAT-1 actively regulates GABA levels.
  • Tonic GABAergic signaling is active and influenced by transporter function even before mature synaptic connections are established.

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