GABAB receptor deficiency causes XXXX in hippocampal networks.

@entity1 @entity410 @entity1246 @entity75 @entity8816 @entity460 @entity12357 @entity528
UNASSIGNED: Stabilization of neuronal activity by homeostatic control systems is fundamental for proper functioning of neural circuits. @entity528 has been hypothesized to underlie common pathophysiological mechanisms in a variety of @entity75 . However, the key molecules regulating homeostasis in central @entity1 neural circuits remain obscure. Here, we show that selective inactivation of GABAB, but not GABAA, receptors impairs firing rate homeostasis by disrupting synaptic homeostatic plasticity in hippocampal networks. Pharmacological GABAB receptor (GABABR) blockade or genetic deletion of the GB1a receptor subunit disrupts homeostatic regulation of synaptic vesicle release. GABABRs mediate adaptive presynaptic enhancement to neuronal inactivity by two principle mechanisms: First, neuronal silencing promotes syntaxin-1 switch from a closed to an open conformation to accelerate soluble @entity8816 -sensitive factor attachment protein receptor (SNARE) complex assembly, and second, it boosts spike-evoked presynaptic @entity460 flux. In both cases, neuronal inactivity removes tonic block imposed by the presynaptic, GB1a-containing receptors on syntaxin-1 opening and @entity460 entry to enhance probability of vesicle fusion. We identified the GB1a intracellular domain essential for the presynaptic homeostatic response by tuning intermolecular interactions among the receptor, syntaxin-1, and the @entity12357 channel. The presynaptic adaptations were accompanied by scaling of excitatory quantal amplitude via the postsynaptic, GB1b-containing receptors. Thus, GABABRs sense chronic perturbations in @entity1246 levels and transduce it to homeostatic changes in synaptic strength. Our results reveal a novel role for GABABR as a key regulator of population firing stability and propose that disruption of homeostatic synaptic plasticity may underlie @entity410 's persistence in the absence of functional GABABRs.
