Regulation of synaptic input to hypothalamic presympathetic neurons by GABAB receptors

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The hypothalamic paraventricular (PVN) neurons projecting to the spinal cord and brainstem play an important role in the control of homeostasis and the sympathetic nervous system. Although GABAB receptors are present in the PVN, their function in the control of synaptic inputs to PVN presympathetic neurons is not clear. Using retrograde tracing and whole-cell patch-clamp recordings in rat brain slices, we determined the role of presynaptic GABAB receptors in regulation of glutamatergic and GABAergic inputs to spinally projecting PVN neurons. The GABAB receptor agonist baclofen (1-50 µM) dose-dependently decreased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) and inhibitory postsynaptic currents (sIPSCs). The effect of baclofen on sEPSCs and sIPSCs was completely blocked by 10 µM CGP52432, a selective GABAB receptor antagonist. Baclofen also significantly reduced the frequency of both miniature excitatory and miniature inhibitory postsynaptic currents (mEPSCs and mIPSCs). Furthermore, uncoupling pertussis toxin-sensitive Gi/o proteins with N-ethylmaleimide abolished baclofen-induced inhibition of mEPSCs and mIPSCs. However, the inhibitory effect of baclofen on the frequency of mIPSCs and mEPSCs persisted in the presence of either Cd2+, a voltage-gated Ca2+ channel blocker, or 4-aminopyridine, a blocker of voltage-gated K+ channels. Our results suggest that activation of presynaptic GABAB receptors inhibits synaptic GABA and glutamate release to PVN presympathetic neurons. This presynaptic action of GABAB receptors is mediated by the N-ethylmaleimide-sensitive Gi/o proteins, but independent of voltage-gated Ca2+ and K+ channels. © 2006 IBRO.

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This article was published in Neuroscience, Volume 142, Issue 2, Pages 595-606.

The published version is available at http://dx.doi.org/10.1016/j.neuroscience.2006.06.039.

Copyright © 2006 Elsevier.

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