Biology subjects

Barnhill, O. K.

Publications and source records attributed to Barnhill, O. K..

3 recordsLinked to original sources

bioRxiv2026

Depolarization block in substantia nigra pars reticulata neurons drives dystonia in a mouse model

Dystonia is a common movement disorder characterized by involuntary co-contraction of antagonist muscles, resulting in abnormal postures. The brain often appears grossly normal, suggesting dysfunctional neural activity as a cause. The basal ganglia are implicated in dystonia, but the causal patterns of neural activity remain unknown. We used a transgenic mouse model of human paroxysmal nonkinesigenic dyskinesia (PNKD), in which ethanol triggers dystonic attacks, to test the role of the substantia nigra pars reticulata (SNr), the primary output nucleus of the basal ganglia in rodents. The firing of SNr neurons was profoundly reduced in vivo during dystonic attacks. Multiple physiological approaches indicated that in PNKD mice, ethanol leads to depolarization block in SNr neurons. Indeed, pulsatile optical activation of inhibitory striatal inputs to SNr rescued firing and attenuated dystonia. In line with theories of basal ganglia dysfunction, these results suggest reduced activity in basal ganglia output nuclei causes dystonia.

neuroscience↗

bioRxiv2025

Ingestion-activated CGRP neurons control learning but not satiety

Calcitonin Gene-Related Peptide (CGRP) neurons in the parabrachial nucleus are critical for sickness and malaise but have also been proposed to control non-aversive (rewarding) satiation. How one cell type can coordinate these opposing processes has not been explained. Here we reinvestigate the function of these cells using single-cell imaging as well as optical and chemogenetic manipulations. Contrary to current models, we show that CGRP neurons do not track cumulative food consumption, and their activity is not necessary for meal termination. Instead, we identify two distinct populations of CGRP cells, one of which responds rapidly to appetitive signals during ingestion and the other of which responds slowly to aversive visceral cues. Surprisingly, the ingestion-activated CGRP neurons are important for learning about post-ingestive effects but have little effect on food consumption. This reveals two populations of CGRP neurons that are sequentially engaged during, and responsible for, the distinct stages of post-ingestive learning.

neuroscience↗

bioRxiv2021

An essential role for a discrete parasubthalamic nucleus subpopulation 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 essential 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, is sufficient to reduce 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 essential, anorexigenic role for PSTNTac1 neurons in the hormonal and central regulation of appetite.

neuroscience↗