Hemispheric specializations are well studied at the functional level but less is known about the underlying neural mechanisms. We identified a small cluster of cholinergic neurons in the dorsal habenula (dHb) of zebrafish, defined by their expression of the lecithin retinol acyltransferase domain containing 2a (lratd2a) gene and their efferent connections with a subregion of the ventral interpeduncular nucleus (vIPN). The lratd2a-expressing neurons in the right dHb are innervated by a subset of mitral cells from both the left and right olfactory bulb and are activated upon exposure to the odorant cadaverine that is repellent to adult zebrafish. Using an intersectional strategy to drive expression of the botulinum neurotoxin specifically in these neurons, we find that adults no longer show aversion to cadaverine. Mutants with left-isomerized dHb that lack these neurons are also less repelled by cadaverine and their behavioral response to alarm substance, a potent aversive cue, is diminished. However, mutants in which both dHb have right identity appear more reactive to alarm substance. The results implicate an asymmetric dHb-vIPN neural circuit in the processing of repulsive olfactory cues and in modulating the resultant behavioral response.
All data generated or analyzed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1-5.Behavioral analyses were performed using custom written scripts in MATLAB and uploaded as Source Code Files.
- Marnie E Halpern
- Marnie E Halpern
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All zebrafish protocols were approved by the Institutional Animal Care and Use Committee (IACUC) of the Carnegie Institution for Science [Protocol #122] or Dartmouth College [Protocol #00002253(m3a)].
- Claire Wyart, Institut du Cerveau et la Moelle épinière, Hôpital Pitié-Salpêtrière, Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, France
© 2021, Choi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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.
The medial prefrontal cortex and amygdala are involved in the regulation of social behavior and associated with psychiatric diseases but their detailed neurophysiological mechanisms at a network level remain unclear. We recorded local field potentials (LFPs) from the dorsal medial prefrontal cortex (dmPFC) and basolateral amygdala (BLA) while male mice engaged on social behavior. We found that in wild-type mice, both the dmPFC and BLA increased 4–7 Hz oscillation power and decreased 30–60 Hz power when they needed to attend to another target mouse. In mouse models with reduced social interactions, dmPFC 4–7 Hz power further increased especially when they exhibited social avoidance behavior. In contrast, dmPFC and BLA decreased 4–7 Hz power when wild-type mice socially approached a target mouse. Frequency-specific optogenetic manipulations replicating social approach-related LFP patterns restored social interaction behavior in socially deficient mice. These results demonstrate a neurophysiological substrate of the prefrontal cortex and amygdala related to social behavior and provide a unified pathophysiological understanding of neuronal population dynamics underlying social behavioral deficits.