A discrete parasubthalamic nucleus subpopulation plays a critical role in appetite suppression.

Food intake behavior is regulated by a network of appetite-inducing and appetite-suppressing neuronal populations throughout the brain. The parasubthalamic nucleus (PSTN), a relatively unexplored population of neurons in the posterior hypothalamus, has been hypothesized to regulate appetite due to its connectivity with other anorexigenic neuronal populations and because these neurons express Fos, a marker of neuronal activation, following a meal. However, the individual cell types that make up the PSTN are not well characterized, nor are their functional roles in food intake behavior. Here, we identify and distinguish between two discrete PSTN subpopulations, those that express tachykinin-1 (PSTNTac1 neurons) and those that express corticotropin-releasing hormone (PSTNCRH neurons), and use a panel of genetically encoded tools in mice to show that PSTNTac1 neurons play an important role in appetite suppression. Both subpopulations increase activity following a meal and in response to administration of the anorexigenic hormones amylin, cholecystokinin (CCK), and peptide YY (PYY). Interestingly, chemogenetic inhibition of PSTNTac1, but not PSTNCRH neurons, reduces the appetite-suppressing effects of these hormones. Consistently, optogenetic and chemogenetic stimulation of PSTNTac1 neurons, but not PSTNCRH neurons, reduces food intake in hungry mice. PSTNTac1 and PSTNCRH neurons project to distinct downstream brain regions, and stimulation of PSTNTac1 projections to individual anorexigenic populations reduces food consumption. Taken together, these results reveal the functional properties and projection patterns of distinct PSTN cell types and demonstrate an anorexigenic role for PSTNTac1 neurons in the hormonal and central regulation of appetite.

Clinical and demographic features of chronic progressive external ophthalmoplegia in a large adult-onset cohort.

Chronic progressive external ophthalmoplegia (CPEO) is a common mitochondrial disease. We evaluated the impact of sex and smoking status upon knee extension strength and the phenotypic spectrum of disease in a large cohort of adult-onset CPEO patients (N=116) using retrospective chart analysis. The CPEO patients showed significantly lower knee extension strength as compared to the age- and sex-matched control population (-37%, P<0.05). Smoking also negatively impacted knee extension strength only in women with CPEO (-26%, P<0.05). We conclude that smoking and female sex interact negatively in CPEO patients.