PMID- 8747195
OWN - NLM
STAT- MEDLINE
DCOM- 19961009
LR  - 20171213
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 74
IP  - 6
DP  - 1995 Dec
TI  - Recruitment of GABAA inhibition in rat neocortex is limited and not NMDA 
      dependent.
PG  - 2329-35
AB  - 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.
FAU - Ling, D S
AU  - Ling DS
AD  - Department of Pharmacology, State University of New York Health Science Center at 
      Brooklyn 11203, USA.
FAU - Benardo, L S
AU  - Benardo LS
LA  - eng
GR  - F32 NS-09534/NS/NINDS NIH HHS/United States
GR  - MH-51677/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (GABA-A Receptor Antagonists)
RN  - 0 (Receptors, GABA-A)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Animals
MH  - Cerebral Cortex/cytology/drug effects/*physiology
MH  - Evoked Potentials/drug effects/physiology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - GABA-A Receptor Antagonists
MH  - Glutamic Acid/physiology
MH  - In Vitro Techniques
MH  - Interneurons/drug effects/physiology
MH  - Patch-Clamp Techniques
MH  - Pyramidal Cells/drug effects/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, GABA-A/*physiology
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*physiology
MH  - Recruitment, Neurophysiological/drug effects/*physiology
MH  - Synapses/drug effects/physiology
MH  - Synaptic Transmission/drug effects/physiology
EDAT- 1995/12/01 00:00
MHDA- 1995/12/01 00:01
CRDT- 1995/12/01 00:00
PHST- 1995/12/01 00:00 [pubmed]
PHST- 1995/12/01 00:01 [medline]
PHST- 1995/12/01 00:00 [entrez]
AID - 10.1152/jn.1995.74.6.2329 [doi]
PST - ppublish
SO  - J Neurophysiol. 1995 Dec;74(6):2329-35. doi: 10.1152/jn.1995.74.6.2329.