Hierarchical Representations of Aggression in a Hypothalamic-Midbrain Circuit.
Ontology highlight
ABSTRACT:
SUBMITTER: Falkner AL
PROVIDER: S-EPMC7571490 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The paraventricular hypothalamus (PVH) regulates stress, feeding behaviors and other homeostatic processes, but whether PVH also drives defensive states remains unknown. Here we showed that photostimulation of PVH neurons in mice elicited escape jumping, a typical defensive behavior. We mapped PVH outputs that densely terminate in the ventral midbrain (vMB) area, and found that activation of the PVH?vMB circuit produced profound defensive behavioral changes, including escape jumping, hiding, hyperlocomotion, and learned aversion. Electrophysiological recordings showed excitatory postsynaptic input onto vMB neurons via PVH fiber activation, and in vivo studies demonstrated that glutamate transmission from PVH?vMB was required for the evoked behavioral responses. Photostimulation of PVH?vMB fibers induced cFos expression mainly in non-dopaminergic neurons. Using a dual optogenetic-chemogenetic strategy, we further revealed that escape jumping and hiding were partially contributed by the activation of midbrain glutamatergic neurons. Taken together, our work unveils a hypothalamic-vMB circuit that encodes defensive properties, which may be implicated in stress-induced defensive responses.
| S-EPMC6664144 | biostudies-literature
Project description:'Sundowning' in dementia and Alzheimer's disease is characterized by early-evening agitation and aggression. While such periodicity suggests a circadian origin, whether the circadian clock directly regulates aggressive behavior is unknown. We demonstrate that a daily rhythm in aggression propensity in male mice is gated by GABAergic subparaventricular zone (SPZGABA) neurons, the major postsynaptic targets of the central circadian clock, the suprachiasmatic nucleus. Optogenetic mapping revealed that SPZGABA neurons receive input from vasoactive intestinal polypeptide suprachiasmatic nucleus neurons and innervate neurons in the ventrolateral part of the ventromedial hypothalamus (VMH), which is known to regulate aggression. Additionally, VMH-projecting dorsal SPZ neurons are more active during early day than early night, and acute chemogenetic inhibition of SPZGABA transmission phase-dependently increases aggression. Finally, SPZGABA-recipient central VMH neurons directly innervate ventrolateral VMH neurons, and activation of this intra-VMH circuit drove attack behavior. Altogether, we reveal a functional polysynaptic circuit by which the suprachiasmatic nucleus clock regulates aggression.
| S-EPMC5920747 | biostudies-literature
Project description:In many vertebrate species, certain individuals will seek out opportunities for aggression, even in the absence of threat-provoking cues. Although several brain areas have been implicated in the generation of attack in response to social threat, little is known about the neural mechanisms that promote self-initiated or 'voluntary' aggression-seeking when no threat is present. To explore this directly, we utilized an aggression-seeking task in which male mice self-initiated aggression trials to gain brief and repeated access to a weaker male that they could attack. In males that exhibited rapid task learning, we found that the ventrolateral part of the ventromedial hypothalamus (VMHvl), an area with a known role in attack, was essential for aggression-seeking. Using both single-unit electrophysiology and population optical recording, we found that VMHvl neurons became active during aggression-seeking and that their activity tracked changes in task learning and extinction. Inactivation of the VMHvl reduced aggression-seeking behavior, whereas optogenetic stimulation of the VMHvl accelerated moment-to-moment aggression-seeking and intensified future attack. These data demonstrate that the VMHvl can mediate both acute attack and flexible seeking actions that precede attack.
| S-EPMC4853470 | biostudies-literature
Project description:Discrimination between predictive and non-predictive threat stimuli decreases as threat intensity increases. The central mechanisms that mediate the transition from discriminatory to generalized threat responding remain poorly resolved. Here, we identify the stress- and dysphoria-associated kappa opioid receptor (KOR) and its ligand dynorphin (Dyn), acting in the ventral tegmental area (VTA), as a key substrate for regulating threat generalization. We identify several dynorphinergic inputs to the VTA and demonstrate that projections from the bed nucleus of the stria terminalis (BNST) and dorsal raphe nucleus (DRN) both contribute to anxiety-like behavior but differentially affect threat generalization. These data demonstrate that conditioned threat discrimination has an inverted "U" relationship with threat intensity and establish a role for KOR/Dyn signaling in the midbrain for promoting threat generalization.
| S-EPMC8511093 | biostudies-literature
Project description:Maternal behaviors are essential for the survival of the young. Previous studies implicated the medial preoptic area (MPOA) as an important region for maternal behaviors, but details of the maternal circuit remain incompletely understood. Here we identify estrogen receptor alpha (Esr1)-expressing cells in the MPOA as key mediators of pup approach and retrieval. Reversible inactivation of MPOAEsr1+ cells impairs those behaviors, whereas optogenetic activation induces immediate pup retrieval. In vivo recordings demonstrate preferential activation of MPOAEsr1+ cells during maternal behaviors and changes in MPOA cell responses across reproductive states. Furthermore, channelrhodopsin-assisted circuit mapping reveals a strong inhibitory projection from MPOAEsr1+ cells to ventral tegmental area (VTA) non-dopaminergic cells. Pathway-specific manipulations reveal that this projection is essential for driving pup approach and retrieval and that VTA dopaminergic cells are reliably activated during those behaviors. Altogether, this study provides new insight into the neural circuit that generates maternal behaviors.
| S-EPMC5890946 | biostudies-literature
Project description:We propose that humans spontaneously organize environments into clusters of states that support hierarchical planning, enabling them to tackle challenging problems by breaking them down into sub-problems at various levels of abstraction. People constantly rely on such hierarchical presentations to accomplish tasks big and small-from planning one's day, to organizing a wedding, to getting a PhD-often succeeding on the very first attempt. We formalize a Bayesian model of hierarchy discovery that explains how humans discover such useful abstractions. Building on principles developed in structure learning and robotics, the model predicts that hierarchy discovery should be sensitive to the topological structure, reward distribution, and distribution of tasks in the environment. In five simulations, we show that the model accounts for previously reported effects of environment structure on planning behavior, such as detection of bottleneck states and transitions. We then test the novel predictions of the model in eight behavioral experiments, demonstrating how the distribution of tasks and rewards can influence planning behavior via the discovered hierarchy, sometimes facilitating and sometimes hindering performance. We find evidence that the hierarchy discovery process unfolds incrementally across trials. Finally, we propose how hierarchy discovery and hierarchical planning might be implemented in the brain. Together, these findings present an important advance in our understanding of how the brain might use Bayesian inference to discover and exploit the hidden hierarchical structure of the environment.
| S-EPMC7162548 | biostudies-literature
Project description:The hippocampus is traditionally thought to transmit contextual information to limbic structures where it acquires valence. Using freely moving calcium imaging and optogenetics, we show that while the dorsal CA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA). Consistent with this selectivity, optogenetic activation of vCA1 terminals in LHA but not BA increased anxiety and avoidance, while activation of terminals in BA but not LHA impaired contextual fear memory. Thus, the hippocampus encodes not only neutral but also valence-related contextual information, and the vCA1-LHA pathway is a direct route by which the hippocampus can rapidly influence innate anxiety behavior.
| S-EPMC5877404 | biostudies-literature
Project description:The homeostatic control of body temperature is essential for survival in mammals and is known to be regulated in part by temperature-sensitive neurons in the hypothalamus. However, the specific neural pathways and corresponding neural populations have not been fully elucidated. To identify these pathways, we used cFos staining to identify neurons that are activated by a thermal challenge and found induced expression in subsets of neurons within the ventral part of the lateral preoptic nucleus (vLPO) and the dorsal part of the dorsomedial hypothalamus (DMD). Activation of GABAergic neurons in the vLPO using optogenetics reduced body temperature, along with a decrease in physical activity. Optogenetic inhibition of these neurons resulted in fever-level hyperthermia. These GABAergic neurons project from the vLPO to the DMD and optogenetic stimulation of the nerve terminals in the DMD also reduced body temperature and activity. Electrophysiological recording revealed that the vLPO GABAergic neurons suppressed neural activity in DMD neurons, and fiber photometry of calcium transients revealed that DMD neurons were activated by cold. Accordingly, activation of DMD neurons using designer receptors exclusively activated by designer drugs (DREADDs) or optogenetics increased body temperature with a strong increase in energy expenditure and activity. Finally, optogenetic inhibition of DMD neurons triggered hypothermia, similar to stimulation of the GABAergic neurons in the vLPO. Thus, vLPO GABAergic neurons suppressed the thermogenic effect of DMD neurons. In aggregate, our data identify vLPO?DMD neural pathways that reduce core temperature in response to a thermal challenge, and we show that outputs from the DMD can induce activity-induced thermogenesis.
| S-EPMC5338448 | biostudies-literature
Project description:Brain signals that govern memory formation remain incompletely identified. The hypothalamus is implicated in memory disorders, but how its rapidly changing activity shapes memorization is unknown. During encounters with objects, hypothalamic melanin-concentrating hormone (MCH) neurons emit brief signals that reflect object novelty. Here we show that targeted optogenetic silencing of these signals, performed selectively during the initial object encounters (i.e. memory acquisition), prevents future recognition of the objects. We identify an upstream inhibitory microcircuit from hypothalamic GAD65 neurons to MCH neurons, which constrains the memory-promoting MCH cell bursts. Finally, we demonstrate that silencing the GAD65 cells during object memory acquisition improves future object recognition through MCH-receptor-dependent pathways. These results provide causal evidence that object-associated signals in genetically distinct but interconnected hypothalamic neurons differentially control whether the brain forms object memories. This gating of memory formation by hypothalamic activity establishes appropriate behavioral responses to novel and familiar objects.
| S-EPMC6555780 | biostudies-literature
Project description:Migraines are a major health burden, but treatment is limited because of inadequate understanding of neural mechanisms underlying headache. Imaging studies of migraine patients demonstrate changes in both pain-modulatory circuits and reward-processing regions, but whether these changes contribute to the experience of headache is unknown. Here, we demonstrate a direct connection between the ventrolateral periaqueductal gray (vlPAG) and the ventral tegmental area (VTA) that contributes to headache aversiveness in rats. Many VTA neurons receive monosynaptic input from the vlPAG, and cranial nociceptive input increases Fos expression in VTA-projecting vlPAG neurons. Activation of PAG inputs to the VTA induces avoidance behavior, while inactivation of these projections induces a place preference only in animals with headache. This work identifies a distinct pathway that mediates cranial nociceptive aversiveness.
| S-EPMC6831085 | biostudies-literature