GABAB receptor deficiency causes failure of neuronal homeostasis in hippocampal networks.

摘要: Stabilization of neuronal activity by homeostatic control systems is fundamental for proper functioning neural circuits. Failure in homeostasis has been hypothesized to underlie common pathophysiological mechanisms a variety brain disorders. However, the key molecules regulating central mammalian circuits remain obscure. Here, we show that selective inactivation GABAB, but not GABA(A), receptors impairs firing rate disrupting synaptic plasticity hippocampal networks. Pharmacological GABA(B) receptor (GABA(B)R) blockade or genetic deletion GB(1a) subunit disrupts regulation vesicle release. GABA(B)Rs mediate adaptive presynaptic enhancement inactivity two principle mechanisms: First, silencing promotes syntaxin-1 switch from closed an open conformation accelerate soluble N-ethylmaleimide-sensitive factor attachment protein (SNARE) complex assembly, and second, it boosts spike-evoked calcium flux. In both cases, removes tonic block imposed presynaptic, GB(1a)-containing on opening entry enhance probability fusion. We identified intracellular domain essential response tuning intermolecular interactions among receptor, syntaxin-1, Ca(V)2.2 channel. The adaptations were accompanied scaling excitatory quantal amplitude via postsynaptic, GB(1b)-containing receptors. Thus, sense chronic perturbations GABA levels transduce changes strength. Our results reveal novel role GABA(B)R as regulator population stability propose disruption may seizure's persistence absence functional GABA(B)Rs.