Activation of metabotropic GABA receptors increases the energy barrier for vesicle fusion

Abstract

SummaryNeurotransmitter release from presynaptic terminals is under the tight control of various metabotropic receptors. We report here that in addition to the regulation of Ca 2+ channel activity, metabotropic GABA B receptors (GABA B Rs) at murine hippocampal glutamatergic synapses utilize an inhibitory pathway that directly targets the synaptic vesicle release machinery. Acute application of the GABA B R agonist baclofen rapidly and reversibly inhibits vesicle fusion, which occurs independently of the SNAP-25 C-terminus. Using applications of hypertonic sucrose solutions, we find that the size of the readily releasable pool remains unchanged by GABA B R activation, but the sensitivity of primed vesicles to hypertonic stimuli appears lowered as the response amplitudes at intermediate sucrose concentrations are smaller and release kinetics are slowed. These data show that presynaptic GABA B Rs can inhibit neurotransmitter release directly by increasing the energy barrier for vesicle fusion.

FABP3 in the Anterior Cingulate Cortex Modulates the Methylation Status of the Glutamic Acid Decarboxylase67Promoter Region

“…In animal studies, it has been shown that the ACC is closely involved in novel object recognition during a task (Weible et al, 2009(Weible et al, , 2012. Specifically, the microinfusion of muscimol, a GABA A receptor agonist, into the ACC immediately before the retrieval phase decreases exploratory behavior toward novel objects (Pezze et al, 2017). In our present and previous studies, Fabp3 KO mice exhibited decreased performance in noveltyseeking (Shimamoto et al, 2014;Yabuki et al, 2018).…”

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