Central regulation of food intake is a key mechanism contributing to energy homeostasis. Many neural circuits that are thought to orchestrate feeding behavior overlap with the brain’s reward ...circuitry both anatomically and functionally. Manipulation of numerous neural pathways can simultaneously influence food intake and reward. Two key systems underlying these processes—those controlling homeostatic and hedonic feeding—are often treated as independent. Homeostatic feeding is necessary for basic metabolic processes and survival, while hedonic feeding is driven by sensory perception or pleasure. Despite this distinction, their functional and anatomical overlap implies considerable interaction that is often overlooked. Here, we argue that the neurocircuits controlling homeostatic feeding and hedonic feeding are not completely dissociable given the current data and urge researchers to assess behaviors extending beyond food intake in investigations of the neural control of feeding.
Rossi and Stuber discuss the entangled neurocircuitry that governs feeding and reward. Using insights from recently developed molecular and genetic tools, the authors argue that homeostatic feeding and hedonic feeding are highly interrelated and urge investigators to measure more than food intake when probing neuronal control of feeding.
The lateral hypothalamic area (LHA) is a subcortical brain region that exerts control over motivated behavior, feeding, and energy balance across species. Recent single-cell sequencing studies have ...defined at least 30 distinct LHA neuron types. Some of these influence specific aspects of energy homeostasis; however, the functions of many LHA cell types remain unclear. This review addresses the rapidly emerging evidence from cell-type-specific investigations that the LHA leverages distinct neuron populations to regulate energy balance through complex connections with other brain regions. It will highlight recent findings demonstrating that LHA control of energy balance extends beyond mere food intake and propose outstanding questions to be addressed by future research.
The brain has long been known to control stress and reward through complex and interconnected circuitry. A new study now reveals a group of hypothalamic neurons that paradoxically mediate both reward ...and aversion.
We examined the contribution of the nigrostriatal DA system to instrumental learning and behavior using optogenetics in awake, behaving mice. Using Cre-inducible channelrhodopsin-2 (ChR2) in mice ...expressing Cre recombinase driven by the tyrosine hydroxylase promoter (Th-Cre), we tested whether selective stimulation of DA neurons in the substantia nigra pars compacta (SNC), in the absence of any natural rewards, was sufficient to promote instrumental learning in naive mice. Mice expressing ChR2 in SNC DA neurons readily learned to press a lever to receive laser stimulation, but unlike natural food rewards the lever pressing did not decline with satiation. When the number of presses required to receive a stimulation was altered, mice adjusted their rate of pressing accordingly, suggesting that the rate of stimulation was a controlled variable. Moreover, extinction, i.e. the cessation of action-contingent stimulation, and the complete reversal of the relationship between action and outcome by the imposition of an omission contingency, rapidly abolished lever pressing. Together these results suggest that selective activation of SNC DA neurons can be sufficient for acquisition and maintenance of a new instrumental action.
The prefrontal cortex is a critical neuroanatomical hub for controlling motivated behaviours across mammalian species. In addition to intra-cortical connectivity, prefrontal projection neurons ...innervate subcortical structures that contribute to reward-seeking behaviours, such as the ventral striatum and midline thalamus. While connectivity among these structures contributes to appetitive behaviours, how projection-specific prefrontal neurons encode reward-relevant information to guide reward seeking is unknown. Here we use in vivo two-photon calcium imaging to monitor the activity of dorsomedial prefrontal neurons in mice during an appetitive Pavlovian conditioning task. At the population level, these neurons display diverse activity patterns during the presentation of reward-predictive cues. However, recordings from prefrontal neurons with resolved projection targets reveal that individual corticostriatal neurons show response tuning to reward-predictive cues, such that excitatory cue responses are amplified across learning. By contrast, corticothalamic neurons gradually develop new, primarily inhibitory responses to reward-predictive cues across learning. Furthermore, bidirectional optogenetic manipulation of these neurons reveals that stimulation of corticostriatal neurons promotes conditioned reward-seeking behaviour after learning, while activity in corticothalamic neurons suppresses both the acquisition and expression of conditioned reward seeking. These data show how prefrontal circuitry can dynamically control reward-seeking behaviour through the opposing activities of projection-specific cell populations.
The habenula complex is appreciated as a critical regulator of motivated and pathological behavioral states via its output to midbrain nuclei. Despite this, transcriptional definition of cell ...populations that comprise both the medial habenular (MHb) and lateral habenular (LHb) subregions in mammals remain undefined. To resolve this, we performed single-cell transcriptional profiling and highly multiplexed in situ hybridization experiments of the mouse habenula complex in naive mice and those exposed to an acute aversive stimulus. Transcriptionally distinct neuronal cell types identified within the MHb and LHb, were spatially defined, differentially engaged by aversive stimuli, and had distinct electrophysiological properties. Cell types identified in mice also displayed a high degree of transcriptional similarity to those previously described in zebrafish, highlighting the well-conserved nature of habenular cell types across the phylum. These data identify key molecular targets within habenular cell types and provide a critical resource for future studies.
•scRNA-seq identifies transcriptional cell types in the mammalian habenula•Zebrafish and mouse habenula are transcriptionally conserved•Topographical and functional organization of transcriptionally defined cell types•Identification of transcriptional cell types in response to aversive stimulus
Whereas anatomy and functions of the habenula have been extensively studied, the transcriptional landscape of the mammalian habenula remains poorly defined. Multimodal analysis of single-cell transcriptomes in the habenula by Hashikawa et al. provides a useful data resource to associate transcriptional diversity with functional relevance of the molecularly defined habenula cell types.
The current obesity epidemic is a major worldwide health concern. Despite the consensus that the brain regulates energy homeostasis, the neural adaptations governing obesity are unknown. Using a ...combination of high-throughput single-cell RNA sequencing and longitudinal in vivo two-photon calcium imaging, we surveyed functional alterations of the lateral hypothalamic area (LHA)-a highly conserved brain region that orchestrates feeding-in a mouse model of obesity. The transcriptional profile of LHA glutamatergic neurons was affected by obesity, exhibiting changes indicative of altered neuronal activity. Encoding properties of individual LHA glutamatergic neurons were then tracked throughout obesity, revealing greatly attenuated reward responses. These data demonstrate how diet disrupts the function of an endogenous feeding suppression system to promote overeating and obesity.
Neural networks that control reproduction must integrate social and hormonal signals, tune motivation, and coordinate social interactions. However, the neural circuit mechanisms for these processes ...remain unresolved. The medial preoptic area (mPOA), an essential node for social behaviors, comprises molecularly diverse neurons with widespread projections. Here we identify a steroid-responsive subset of neurotensin (Nts)-expressing mPOA neurons that interface with the ventral tegmental area (VTA) to form a socially engaged reward circuit. Using in vivo two-photon imaging in female mice, we show that mPOA
neurons preferentially encode attractive male cues compared to nonsocial appetitive stimuli. Ovarian hormone signals regulate both the physiological and cue-encoding properties of these cells. Furthermore, optogenetic stimulation of mPOA
-VTA circuitry promotes rewarding phenotypes, social approach and striatal dopamine release. Collectively, these data demonstrate that steroid-sensitive mPOA neurons encode ethologically relevant stimuli and co-opt midbrain reward circuits to promote prosocial behaviors critical for species survival.
Jump processes as generalized gradient flows Peletier, Mark A.; Rossi, Riccarda; Savaré, Giuseppe ...
Calculus of variations and partial differential equations,
02/2022, Letnik:
61, Številka:
1
Journal Article
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We have created a functional framework for a class of non-metric gradient systems. The state space is a space of nonnegative measures, and the class of systems includes the Forward Kolmogorov ...equations for the laws of Markov jump processes on Polish spaces. This framework comprises a definition of a notion of solutions, a method to prove existence, and an archetype uniqueness result. We do this by using only the structure that is provided directly by the dissipation functional, which need not be homogeneous, and we do not appeal to any metric structure.
Oxytocin (OT) is critical for the expression of social behavior across a wide array of species; however, the role of this system in the encoding of socially relevant information is not well ...understood. In the present study, we show that chemogenetic activation of OT neurons within the paraventricular nucleus of the hypothalamus (PVH) of male mice (OT-Ires-Cre) enhanced social investigation during a social choice test, while chemogenetic inhibition of these neurons abolished typical social preferences. These data suggest that activation of the OT system is necessary to direct behavior preferentially toward social stimuli. To determine whether the presence of a social stimulus is sufficient to induce activation of PVH-OT neurons, we performed the first definitive recording of OT neurons in awake mice using two-photon calcium imaging. These recordings demonstrate that social stimuli activate PVH-OT neurons and that these neurons differentially encode social and nonsocial stimuli, suggesting that PVH-OT neurons may act to convey social salience of environmental stimuli. Finally, an attenuation of social salience is associated with social disorders, such as autism. We therefore also examined possible OT system dysfunction in a mouse model of autism,
knock-out (KO) mice. Male
KO mice showed a marked reduction in PVH-OT neuron number and administration of an OT receptor agonist improved social deficits. Overall, these data suggest that the presence of a social stimulus induces activation of the PVH-OT neurons to promote adaptive social behavior responses.
Although the oxytocin (OT) system is well known to regulate a diverse array of social behaviors, the mechanism in which OT acts to promote the appropriate social response is poorly understood. One hypothesis is that the presence of social conspecifics activates the OT system to generate an adaptive social response. Here, we selectively recorded from OT neurons in the paraventricular hypothalamic nucleus (PVH) to show that social stimulus exposure indeed induces activation of the OT system. We also show that activation of the OT system is necessary to promote social behavior and that mice with abnormal social behavior have reduced numbers of PVH-OT neurons. Finally, aberrant social behavior in these mice was rescued by administration of an OT receptor agonist.
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