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Visual deprivation by dark rearing in kittens and monkeys delays visual pathway development and prolongs the critical period. In contrast, receptive fields (RFs) in superior colliculus (SC) of Syrian hamsters (Mesocricetus auratus) refine normally with spontaneous activity alone, requiring only brief juvenile visual experience to maintain refined RFs in adulthood (Carrasco et al., 2005). Extending dark rearing past puberty leads to lower GAD and GABA levels due to reduced BDNF-TrkB signaling, resulting in RF re-enlargement (Carrasco et al., 2011; Mudd et al., 2019). Previous studies in kittens and monkeys have reported that dark rearing is associated with changes in both GABA ligand and GABA-Areceptor levels. Given the reduced GABA levels in SC of dark reared adult hamsters, we asked if dark rearing also causes changes in GABA_Areceptor levels. We examined expression of GABA_Areceptor subunits, their anchoring protein gephyrin, and the cation-chloride co-transporters KCC2 and NKCC1 in dark reared hamsters. Surprisingly, we found that dark rearing from birth until puberty had no effect on the levels of any of these postsynaptic elements, revealing a new form of maladaptive, presynaptic only inhibitory plasticity in which, rather than extending the critical period as seen in kittens and monkeys, hamster receptive fields refine normally and then lose refinement in adulthood. These results suggest that attempts to increase plasticity in adulthood for rehabilitation or recovery from injury should consider the possibility of unintended negative consequences. In addition, our results demonstrate the interesting finding that changes in neurotransmitter levels are not necessarily coordinated with changes in postsynaptic components. 

Gordon Holmes syndrome (GHS) is a neurological disorder associated with neuroendocrine, cognitive, and motor impairments with corresponding neurodegeneration. Mutations in the E3 ubiquitin ligaseRNF216are strongly linked to GHS. Previous studies show that deletion ofRnf216in mice led to sex-specific neuroendocrine dysfunction due to disruptions in the hypothalamic–pituitary–gonadal axis. To address RNF216 action in cognitive and motor functions, we testedRnf216knock-out (KO) mice in a battery of motor and learning tasks for a duration of 1 year. Although male and female KO mice did not demonstrate prominent motor phenotypes, KO females displayed abnormal limb clasping. KO mice also showed age-dependent strategy and associative learning impairments with sex-dependent alterations of microglia in the hippocampus and cortex. Additionally, KO males but not females had more negative resting membrane potentials in the CA1 hippocampus without any changes in miniature excitatory postsynaptic current (mEPSC) frequencies or amplitudes. Our findings show that constitutive deletion ofRnf216alters microglia and neuronal excitability, which may provide insights into the etiology of sex-specific impairments in GHS.