Journal article
GABA(B)-mediated inhibition of multiple modes of glutamate release in the nucleus of the solitary tract
Journal of neurophysiology, Vol.106(4), pp.1833-1840
10/2011
Handle:
https://hdl.handle.net/2376/102538
PMID: 21734101
Abstract
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.
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Details
- Title
- GABA(B)-mediated inhibition of multiple modes of glutamate release in the nucleus of the solitary tract
- Creators
- Jessica A Fawley - Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon, USA. fawley.jessica@gmail.comJames H PetersMichael C Andresen
- Publication Details
- Journal of neurophysiology, Vol.106(4), pp.1833-1840
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- United States
- Grant note
- R01 HL105703 / NHLBI NIH HHS HL-041119 / NHLBI NIH HHS R01 HL041119 / NHLBI NIH HHS HL-088894 / NHLBI NIH HHS F32 HL088894 / NHLBI NIH HHS HL-105703 / NHLBI NIH HHS
- Identifiers
- 99900546672201842
- Language
- English
- Resource Type
- Journal article