Presynaptic GABAB receptors modulate thalamic excitation of inhibitory and excitatory neurons in the mouse barrel cortex.
Cortical inhibition plays an important role in the processing of sensory information, and the enlargement of receptive fields by the in vivo application of GABAB receptor antagonists indicates that GABAB receptors mediate some of this cortical inhibition. Although there is evidence of postsynaptic GABAB receptors on cortical neurons, there is no evidence of GABAB receptors on thalamocortical terminals. Therefore to determine if presynaptic GABAB receptors modulate the thalamic excitation of layer IV inhibitory neurons and excitatory neurons in layers II-III and IV of the somatosensory "barrel" cortex of mice, we used a thalamocortical slice preparation and patch-clamp electrophysiology. Stimulation of the ventrobasal thalamus elicited excitatory postsynaptic currents (EPSCs) in cortical neurons. Bath application of baclofen, a selective GABAB receptor agonist, reversibly decreased AMPA receptor-mediated and N-methyl-D-aspartate (NMDA) receptor-mediated EPSCs in inhibitory and excitatory neurons. The GABAB receptor antagonist, CGP 35348, reversed the inhibition produced by baclofen. Blocking the postsynaptic GABAB receptor-mediated effects with a Cs+ -based recording solution did not affect the inhibition, suggesting a presynaptic effect of baclofen. Baclofen reversibly increased the paired-pulse ratio and the coefficient of variation, consistent with the presynaptic inhibition of glutamate release. Our results indicate that the presynaptic activation of GABAB receptors modulates thalamocortical excitation of inhibitory and excitatory neurons and provide another mechanism by which cortical inhibition can modulate the processing of sensory information.
Porter
James T
JT
Department of Pharmacology and Toxicology, Ponce School of Medicine, Ponce, Puerto Rico, 00732. jporter@psm.edu.
Nieves
Dalila
D
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002540:Cerebral Cortex / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013788:Thalamus / Q000502:physiology*
D018080:Receptors, GABA-B; D016194:Receptors, N-Methyl-D-Aspartate; D001418:Baclofen