Presynaptic GABA_B Receptors Modulate Thalamic Excitation of Inhibitory and Excitatory Neurons in the Mouse Barrel Cortex

Abstract

Porter, James T. and Dalila Nieves. Presynaptic GABA B receptors modulate thalamic excitation of inhibitory and excitatory neurons in the mouse barrel cortex. J Neurophysiol 92: 2762-2770, 2004. First published July 14, 2004 10.1152/jn.00196.2004. Cortical inhibition plays an important role in the processing of sensory information, and the enlargement of receptive fields by the in vivo application of GABA B receptor antagonists indicates that GABA B receptors mediate some of this cortical inhibition. Although there is evidence of postsynaptic GABA B receptors on cortical neurons, there is no evidence of GABA B receptors on thalamocortical terminals. Therefore to determine if presynaptic GABA B 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 GABA B receptor agonist, reversibly decreased AMPA receptor-mediated and N-methyl-D-aspartate (NMDA) receptor-mediated EPSCs in inhibitory and excitatory neurons. The GABA B receptor antagonist, CGP 35348, reversed the inhibition produced by baclofen. Blocking the postsynaptic GABA B receptormediated effects with a Cs ϩ -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 GABA B receptors modulates thalamocortical excitation of inhibitory and excitatory neurons and provide another mechanism by which cortical inhibition can modulate the processing of sensory information.

Increased Excitability of Somatosensory Cortex in Aged Humans is Associated with Impaired Tactile Acuity

“…In the visual cortex, suppression is also more consistent with thalamocortical synaptic depression than with inhibition Freeman et al, 2002). In addition, there is evidence that GABA B receptors seem to be involved in regulation of PPS (Porter and Nieves, 2004). Recently, an altered composition of GABA A receptors, especially a reduction of subunit ␣ 5, has been reported in aged animals (Schmidt et al, 2010).…”

Modulation of synaptic function through the α-neurexin–specific ligand neurexophilin-1

“…Therefore, the recruitment of (additional) postsynaptic GABA A R triggered by our ectopic expression of Nxph1 may enhance a natural process and thus explain the alterations of shortterm plasticity as observed in our study. Moreover, coactivation of presynaptic GABA B R at the transgenic excitatory synapses may curtail glutamate release itself, thus further decreasing the possiblity of facilitation (55). In fact, this regulatory action of presynaptic GABA B R is well-documented for many excitatory and inhibitory synapses (55)(56)(57)(58)(59)(60), suggesting that recruitment of (additional) presynaptic GABA B R triggered by our ectopic expression of Nxph1 may again only enhance a natural process.…”

“…Moreover, coactivation of presynaptic GABA B R at the transgenic excitatory synapses may curtail glutamate release itself, thus further decreasing the possiblity of facilitation (55). In fact, this regulatory action of presynaptic GABA B R is well-documented for many excitatory and inhibitory synapses (55)(56)(57)(58)(59)(60), suggesting that recruitment of (additional) presynaptic GABA B R triggered by our ectopic expression of Nxph1 may again only enhance a natural process. Finally, in both mouse models and types of synapses investigated, evoked release (eIPSC in NRT and eEPSC in neocortex) was unchanged over a range of stimulation strengths, suggesting that the efficiency of .…”

Tonic Activation of GABAB Receptors Reduces Release Probability at Inhibitory Connections in the Cerebellar Glomerulus

“…Although a tonic presynaptic inhibition of neurotransmitter release by GABA B receptor was also reported at other central synapses (Chen and Yung 2005;Fearon 2003;Jensen et al 1999;Morishita and Sastry 1995;Mouginot et al 1998;Porter and Nieves 2004), in the cerebellar glomerulus this mechanism would benefit from restricted neurotransmitter diffusion, which can also favor cross talk between glutamatergic and GABAergic terminals. In particular, metabotropic glutamate receptors can inhibit GABA release from Golgi cell terminals and GABA B receptors can inhibit glutamate release from mossy fiber (Mitchell and Silver 2000a,b).…”