GABAB receptors mediate frequency-dependent depression of excitatory potentials in rat perirhinal cortex in vitro.
Excitatory synaptic transmission in the perirhinal cortex exhibits marked homosynaptic paired pulse depression (PPD) at inter-pulse intervals between 100 and 1000 ms, being maximal at 200 ms. Additionally, there is greater PPD with stimulation of the pathway from the temporal cortex side than with stimulation of the pathway from the entorhinal cortex side. We establish that this frequency-dependent depression relies on the activation of GABAB (gamma-aminobutyric acid) receptors. PPD in both temporal and entorhinal pathways is abolished by either of the selective GABAB receptor antagonists, 3-N[1-(S)-(3, 4-dichlorophenyl)ethyl]amino-2-(S)-hydroxypropyl-p-benzyl-phosphinic acid (CGP55845A) or 3-amino-propyl(diethoxymethyl)phosphinic acid (CGP35348). Barium which blocks G-protein-coupled, inwardly rectifying potassium channels, does not block PPD. Heterosynaptic depression mediated by GABAB receptors was also observed. The depression of the entorhinal pathway by stimulation of the temporal pathway is greater than depression of the temporal pathway by stimulation of the entorhinal pathway. Moreover, PPD increases with stimulus strength and the depression is enhanced by short trains of stimuli, consistent with stronger stimulation resulting in more GABA reaching GABAB receptors on excitatory glutamatergic synapses. Synaptic activation of GABAB receptors may be important in regulating excitability in a frequency-dependent manner with maximal depression occurring at approximately 5 Hz, which approximates to the theta rhythm. That homosynaptic and heterosynaptic depression by stimulation of the temporal pathway is greater than by stimulation of the entorhinal pathway suggests that activation of temporal feedforward connections to the perirhinal cortex can dominate the GABAergic control of synaptic activity within the perirhinal cortex.
Ziakopoulos
Z
Z
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol BS8 1TD, UK.
Brown
M W
MW
Bashir
Z I
ZI
D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005246:Feedback / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010721:Phosphinic Acids / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D018080:Receptors, GABA-B / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D013702:Temporal Lobe / Q000502:physiology
D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D010721:Phosphinic Acids; D015221:Potassium Channels; D011412:Propanolamines; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; D018047:Receptors, Purinergic P1; C085075:CGP 55845A; C066430:CGP 35348; D019204:GTP-Binding Proteins