The role of amygdaloid glutamatergic receptors (GluRs) in maintenance of the sensory versus emotional component of neuropathic pain was studied by assessing monofilament-induced limb withdrawal response (sensory pain) and aversive place-conditioning behavior (emotional pain) following amygdaloid administration of various glutamatergic compounds in nerve-injured animals. The results indicate that endogenous activation of amygdaloid group I metabotropic GluRs, mGluR(1) and mGluR(5), and the NMDA-R contributes to maintenance of sensory and emotional components of neuropathic pain. The predominant effect by amygdaloid group I mGluRs was facilitation of emotional-like pain behavior.
Spermatogenesis-associated protein 13 (
Spata13
) is a guanine nucleotide exchange factor (GEF) enriched in discrete brain regions in the adult, with pronounced expression in the extended central amygdala (CeA). Loss of
Spata13
, also known as the adenomatous polyposis coli exchange factor
Asef2
, has no identifiable phenotype although it has been shown to reduce the number and size of intestinal tumours in Apc (Min/+) mice. Nevertheless, its brain-related functions have not been investigated. To pursue this, we have generated a
Spata13
knockout mouse line using CRISPR-mediated deletion of an exon containing the GTPase domain that is common to multiple isoforms. Homozygous mutants were viable and appeared normal. We subjected both male and female cohorts to a comprehensive battery of behavioural tests designed to investigate particular CeA-related functions. Here, we show that
Spata13
modulates social behaviour with homozygous mutants being subordinate to wildtype controls. Furthermore, female homozygotes show increased activity in home cages during the dark phase of the light–dark cycle. In summary,
Spata13
modulates social hierarchy in both male and female mice in addition to affecting voluntary activity in females.
Switches between global sleep and wakefulness states are believed to be dictated by top-down influences arising from subcortical nuclei. Using forward genetics and in vivo electrophysiology, we identified a recessive mouse mutant line characterized by a substantially reduced propensity to transition between wake and sleep states with an especially pronounced deficit in initiating rapid eye movement (REM) sleep episodes. The causative mutation, an Ile102Asn substitution in the synaptic vesicular protein, VAMP2, was associated with morphological synaptic changes and specific behavioral deficits, while in vitro electrophysiological investigations with fluorescence imaging revealed a markedly diminished probability of vesicular release in mutants. Our data show that global shifts in the synaptic efficiency across brain-wide networks leads to an altered probability of vigilance state transitions, possibly as a result of an altered excitability balance within local circuits controlling sleep-wake architecture.
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