Recruitment of GABAA inhibition in rat neocortex is limited and not NMDA dependent

J Neurophysiol. 1995 Dec;74(6):2329-35. doi: 10.1152/jn.1995.74.6.2329.

Abstract

1. The recruitment of evoked fast inhibitory postsynaptic currents (IPSCs) and excitatory postsynaptic currents (EPSCs) was examined using whole cell voltage-clamp recordings from layer V pyramidal neurons in slices of rat somatosensory cortex. Synaptic currents were evoked with graded electrical stimulation to assess the relative activation of IPSCs and EPSCs. Fast GABAA ergic IPSCs were selectively recorded by holding cells at potentials equal to EPSC reversal (approximately 0 mV). EPSCs were likewise isolated by holding cells at IPSC reversal potential (about -75 mV). 2. As stimulus intensities were increased, the magnitude of the postsynaptic currents also increased. Over the range of stimuli applied (2-10 V), EPSCs did not exhibit an upper limit. However, fast gamma-aminobutyric acid-A (GABAA-mediated IPSCs reached a maximum at intensities approximately 2 times threshold. 3. The limit on fast inhibition was unresponsive to alterations in N-methyl-D-aspartate (NMDA)-mediated excitation. Exposure to nominally magnesium-free solutions or to the NMDA antagonist 3-[(RS)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid did not affect the fast IPSC maximum. Shifts in the input-output curves for submaximal activation of IPSCs were seen, which were attributed to polysynaptic excitation. 4. Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (non-NMDA) receptors with 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) completely abolished synaptically driven, fast GABAA-mediated inhibition. These findings suggested that neocortical inhibitory cells could be driven exclusively through non-NMDA transmission. 5. By comparison, in hippocampal CA1 pyramidal neurons maximal fast inhibition was sensitive to both NMDA and non-NMDA receptor blockade. 6. The results in neocortex were corroborated by direct intracellular recordings from layer V-VI interneurons. Non-NMDA receptor blockade with CNQX prevented synaptic activation of action potentials in these cells, even during cotreatment with magnesium-free solution. 7. Together, these results suggest that recruitment of GABA(A) ergic IPSCs in neocortex is ultimately driven via glutamatergic afferents arriving at non-NMDA receptors on interneurons. Properties limiting fast inhibition would favor the propagation of enhanced excitatory activity through the neuronal network.

Publication types

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

MeSH terms

  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Evoked Potentials / drug effects
  • Evoked Potentials / physiology
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA-A Receptor Antagonists
  • Glutamic Acid / physiology
  • In Vitro Techniques
  • Interneurons / drug effects
  • Interneurons / physiology
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / physiology*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Recruitment, Neurophysiological / drug effects
  • Recruitment, Neurophysiological / physiology*
  • Synapses / drug effects
  • Synapses / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Excitatory Amino Acid Antagonists
  • GABA-A Receptor Antagonists
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid