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Neurons in the lateral hypothalamic area that express hypocretin (Hcrt) neuropeptides help regulate many behaviors including wakefulness and reward seeking. These neurons project throughout the brain, including to neural populations that regulate wakefulness, such as the locus coeruleus (LC) and tuberomammilary nucleus (TMN), as well as to populations that regulate reward, such as the nucleus accumbens (NAc) and ventral tegmental area (VTA). To address the roles of Hcrt neurons in seemingly disparate behaviors, it has been proposed that Hcrt neurons can be anatomically subdivided into at least two distinct subpopulations: a “medial group” that projects to the LC and TMN, and a “lateral group” that projects to the NAc and VTA. Here, we use a dual retrograde tracer strategy to test the hypotheses that Hcrt neurons can be classified based on their downstream projections and medial/lateral location within the hypothalamus. We found that individual Hcrt neurons were significantly more likely to project to both the LC and TMN or to both the VTA and NAc than would be predicted by chance. In contrast, we found that Hcrt neurons that projected to the LC or TMN were mostly distinct from Hcrt neurons that projected to the VTA or NAc. Interestingly, these two populations of Hcrt neurons are intermingled within the hypothalamus and cannot be classified into medial or lateral groups. These results suggest that Hcrt neurons can be distinguished based on their downstream projections but are intermingled within the hypothalamus.

 

Mus musculus enters a torpid state in response to caloric restriction in sub-thermoneutral ambient temperatures. This torpid state is characterized by an adaptive and controlled decrease in metabolic rate, heart rate, body temperature, and activity. Previous research has identified the paraventricular nucleus (PVN) within the hypothalamus, a region containing oxytocin neurons, as a location that is active during torpor onset. We hypothesized that oxytocin neurons within the PVN are part of this neural circuit and that activation of oxytocin neurons would deepen and lengthen torpor bouts. We report that activation of oxytocin neurons alone is not sufficient to induce a torpor-like state in the fed mouse, with no significant difference in body temperature or heart rate upon activation of oxytocin neurons. However, we found that activation of oxytocin neurons prior to the onset of daily torpor both deepens and lengthens the subsequent bout, with a 1.7 ± 0.4 °C lower body tempera- ture and a 135 ± 32 min increase in length. We therefore conclude that oxytocin neurons are involved in the neural circuitry controlling daily torpor in the mouse. 

The parabrachial nucleus (PBN) is a major hub that receives sensory information from both internal and external environments. Specific populations of PBN neurons are involved in behaviors including food and water intake, nociceptive responses, breathing regulation, as well as learning and responding appropriately to threatening stimuli. However, it is unclear how many PBN neuron populations exist and how different behaviors may be encoded by unique signaling molecules or receptors. Here we provide a repository of data on the molecular identity, spatial location, and projection patterns of dozens of PBN neuron subclusters. Using single-cell RNA sequencing, we identified 21 subclusters of neurons in the PBN and neighboring regions. Multiplexed in situ hybridization showed many of these subclusters are enriched within specific PBN subregions with scattered cells in several other regions. We also provide detailed visualization of the axonal projections from 21 Cre-driver lines of mice. These results are all publicly available for download and provide a foundation for further interrogation of PBN functions and connections. 

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 (PSTN Tac1 neurons) and those that express corticotropin-releasing hormone (PSTN CRH neurons), and use a panel of genetically encoded tools in mice to show that PSTN Tac1 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 PSTN Tac1 , but not PSTN CRH neurons, reduces the appetite-suppressing effects of these hormones. Consistently, optogenetic and chemogenetic stimulation of PSTN Tac1 neurons, but not PSTN CRH neurons, reduces food intake in hungry mice. PSTN Tac1 and PSTN CRH neurons project to distinct downstream brain regions, and stimulation of PSTN Tac1 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 PSTN Tac1 neurons in the hormonal and central regulation of appetite. 

Abstract The sleep disorder narcolepsy is associated with symptoms related to either boundary state control that include excessive daytime sleepiness and sleep fragmentation, or rapid eye movement (REM) sleep features including cataplexy, sleep paralysis, hallucinations, and sleep-onset REM sleep events (SOREMs). Although the loss of Hypocretin/Orexin (Hcrt/Ox) peptides or their receptors have been associated with the disease, here we propose a circuit perspective of the pathophysiological mechanisms of these narcolepsy symptoms that encompasses brain regions, neuronal circuits, cell types, and transmitters beyond the Hcrt/Ox system. We further discuss future experimental strategies to investigate brain-wide mechanisms of narcolepsy that will be essential for a better understanding and treatment of the disease.