Aberrant processing of auditory stimuli is a prominent feature of schizophrenia (SZ). Prior studies have chronicled histological abnormalities in the auditory cortex of SZ subjects, but whether deficits exist at upstream, subcortical levels has yet to be established. En route to the auditory cortex, ascending information is integrated in the inferior colliculus (IC), a highly gamma amino butyric acid (GABA) ergic midbrain structure that is critically involved in auditory processing. The IC contains a dense population of parvalbumin-immunoreactive interneurons (PVIs), a cell type characterized by increased metabolic demands and enhanced vulnerability to oxidative stress. During development, PVIs are preferentially surrounded by perineuronal nets (PNNs), specialized extracellular matrix structures that promote redox homeostasis and excitatory/inhibitory balance. Moreover, in SZ, deficits in PVIs, PNNs, and the GABA synthesizing enzyme, glutamic acid decarboxylase (Gad67), have been extensively documented in cortical regions. Yet, whether similar impairments exist in the IC is currently unknown. Thus, we compared IC samples of age- and sex-matched pairs of SZ and unaffected control subjects. SZ subjects exhibited lower levels of Gad67 immunoreactivity and a decreased density of PVIs and PNNs within the IC. These findings provide the first histological evidence of IC GABAergic abnormalities in SZ and suggest that SZ-related auditory dysfunction may stem, in part, from altered IC inhibitory tone.

Selenium (Se) is an essential micronutrient of critical importance to mammalian life. Its biological effects are primarily mediated via co-translational incorporation into selenoproteins, as the unique amino acid, selenocysteine. These proteins play fundamental roles in redox signaling and includes the glutathione peroxidases and thioredoxin reductases. Environmental distribution of Se varies considerably worldwide, with concomitant effects on Se status in humans and animals. Dietary Se intake within a narrow range optimizes the activity of Se-dependent antioxidant enzymes, whereas both Se-deficiency and Se-excess can adversely impact health. Se-deficiency affects a significant proportion of the world's population, with hypothyroidism, cardiomyopathy, reduced immunity, and impaired cognition being common symptoms. Although relatively less prevalent, Se-excess can also have detrimental consequences and has been implicated in promoting both metabolic and neurodegenerative disease in humans. Herein, we sought to comprehensively assess the developmental effects of both Se-deficiency and Se-excess on a battery of neurobehavioral and metabolic tests in mice. Se-deficiency elicited deficits in cognition, altered sensorimotor gating, and increased adiposity, while Se-excess was surprisingly beneficial.

Contextual fear learning is heavily dependent on the hippocampus. Despite evidence that catecholamines contribute to contextual encoding and memory retrieval, the precise temporal dynamics of their release in the hippocampus during behavior is unknown. In addition, new animal models are required to probe the effects of altered catecholamine synthesis on release dynamics and contextual learning. Utilizing GRABNE and GRABDA sensors, in vivo fiber photometry, and two new mouse models of altered locus coeruleus norepinephrine (LC-NE) synthesis, we investigate norepinephrine (NE) and dopamine (DA) release dynamics in dorsal hippocampal CA1 during contextual fear conditioning. We report that aversive foot-shock increases both NE and DA release in dorsal CA1, while freezing behavior associated with recall of fear memory is accompanied by decreased release. Partial loss of LC-NE synthesis reveals that NE release dynamics are modulated by sex. Moreover, we find that recall of recent fear memory is sensitive to both partial and complete loss of LC-NE synthesis throughout prenatal and postnatal development, similar to prior observations of mice with global loss of NE synthesis beginning postnatally. In contrast, remote recall is compromised only by complete loss of LC-NE synthesis beginning prenatally. Overall, these findings provide novel insights into the role of NE in contextual fear and the precise temporal dynamics of both NE and DA during freezing behavior, and highlight a complex relationship between genotype, sex, and NE signaling.