title: GABA(B) receptor-mediated heterosynaptic depression of excitatory synaptic transmission in rat frontal neocortex.
abstract: Neocortical synapses display several forms of short-term plasticity including paired-pulse facilitation and depression. The mechanisms underlying this diversity are unclear. Synaptic currents in response to paired stimulation were recorded from layer II/III pyramidal neurons in rat frontal neocortical slices using the whole-cell patch-clamp method. Both paired-pulse facilitation (PPF) and paired-pulse depression (PPD) were observed in control saline. In the presence of 10 microM bicuculline (BIC), prominent PPD was consistently elicited. The maximal depression of the second EPSC occurred around 100 ms although PPD was still observed at intervals up to 1500 ms. Manipulations that reduced the probability of transmitter release significantly affected PPD. Both conditioning (C)- and test (T)-EPSCs were reduced when the extracellular Ca(2+) concentration was lowered from 3 to 1 mM. The decrease was greater in the C-EPSC resulting in a decrease in PPD. The gamma-aminobutyric acid (GABA)(B) receptor agonist baclofen (10 microM) reduced the amplitude of both evoked EPSCs and changed PPD to PPF. In the presence of the GABA(B) antagonists 2(OH)-saclofen (200-400 microM) or SCH50911 (10 microM), PPF was commonly observed. The metabotropic glutamate receptor antagonist MCPG (500 microM) had no effect on neocortical PPD. Brief stimulus trains induced a progressive depression that was insensitive to GABA(B) antagonists. Paired-pulse depression of excitatory synaptic transmission is a prominent phenomenon in frontal neocortex. At least two components of depression were observed. They may play an important role in regulating the balance between excitation and inhibition, therefore maintaining stability in cortical circuits.
authors.affiliation: Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294-0021, USA.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Chu
authors.forename: John J
authors.initials: JJ
authors.lastname: Hablitz
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019579:Neocortex / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013995:Time
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B; D017661:Receptors, Presynaptic