Open AccessGABAB-mediated inhibition of multiple modes of glutamate release in the nucleus of the solitary tract
Author(s) -
Jessica A. Fawley,
James H. Peters,
Michael Andresen
Publication year - 2011
Publication title -
journal of neurophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.302
H-Index - 245
eISSN - 1522-1598
pISSN - 0022-3077
DOI - 10.1152/jn.00476.2011
Subject(s) - excitatory postsynaptic potential , chemistry , glutamate receptor , trpv1 , neuroscience , solitary tract , glutamatergic , inhibitory postsynaptic potential , biophysics , nucleus , receptor , transient receptor potential channel , biology , biochemistry
In the caudal portions of the solitary tract (ST) nucleus, primary sensory afferents fall into two broad classes based on the expression of transient receptor potential vanilloid type 1 (TRPV1) receptors. Both afferent classes (TRPV1+/-) have indistinguishable glutamate release mechanisms for ST-evoked excitatory postsynaptic currents (EPSCs). However, TRPV1+ terminals release additional glutamate from a unique, TRPV1-operated vesicle pool that is temperature sensitive and facilitated by ST activity to generate asynchronous EPSCs. This study tested whether presynaptic γ-aminobutyric acid (GABA)(B) receptors inhibit both the evoked and TRPV1-operated release mechanisms on second-order ST nucleus neurons. In horizontal slices, shocks activated single ST axons and evoked the time-invariant (latency jitter <200 μs), glutamatergic EPSCs, which identified second-order neurons. Gabazine eliminated GABA(A) responses in all recordings. The GABA(B) agonist baclofen inhibited the amplitude of ST-EPSCs from both TRPV1+ and TRPV1- afferents with a similar EC(50) (∼1.2 μM). In TTX, GABA(B) activation decreased miniature EPSC (mEPSC) rates but not amplitudes, suggesting presynaptic actions downstream from terminal excitability. With calcium entry through voltage-activated calcium channels blocked by cadmium, baclofen reduced mEPSC frequency, indicating that GABA(B) reduced vesicle release by TRPV1-dependent calcium entry. GABA(B) activation also reduced temperature-evoked increases in mEPSC frequency, which relies on TRPV1. Our studies indicate that GABA(B) G protein-coupled receptors are uniformly distributed across all ST primary afferent terminals and act at multiple stages of the excitation-release cascades to suppress both action potential-triggered and TRPV1-coupled glutamate transmission pathways. Moreover, the segregated release cascades within TRPV1+ ST primary afferents represent independent, potential targets for differential modulation.