Heterogeneous Habenular Neuronal Ensembles during Selection of Defensive Behaviors.
Ontology highlight
ABSTRACT:
SUBMITTER: Lecca S
PROVIDER: S-EPMC7296347 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The ventral tegmental area (VTA) has dopamine, GABA, and glutamate neurons, which have been implicated in reward and aversion. Here, we determined whether VTA-glutamate or -GABA neurons play a role in innate defensive behavior. By VTA cell-type-specific genetic ablation, we found that ablation of glutamate, but not GABA, neurons abolishes escape behavior in response to threatening stimuli. We found that escape behavior is also decreased by chemogenetic inhibition of VTA-glutamate neurons and detected increases in activity in VTA-glutamate neurons in response to the threatening stimuli. By ultrastructural and electrophysiological analysis, we established that VTA-glutamate neurons receive a major monosynaptic glutamatergic input from the lateral hypothalamic area (LHA) and found that photoinhibition of this input decreases escape responses to threatening stimuli. These findings indicate that VTA-glutamate neurons are activated by and required for innate defensive responses and that information on threatening stimuli to VTA-glutamate neurons is relayed by LHA-glutamate neurons.
| S-EPMC7381361 | biostudies-literature
Project description:The formation of the embryonic brain requires the production, migration, and differentiation of neurons to be timely and coordinated. Coupling to the photoperiod could synchronize the development of neurons in the embryo. Here, we consider the effect of light and melatonin on the differentiation of embryonic neurons in zebrafish. We examine the formation of neurons in the habenular nuclei, a paired structure found near the dorsal surface of the brain adjacent to the pineal organ. Keeping embryos in constant darkness causes a temporary accumulation of habenular precursor cells, resulting in late differentiation and a long-lasting reduction in neuronal processes (neuropil). Because constant darkness delays the accumulation of the neurendocrine hormone melatonin in embryos, we looked for a link between melatonin signaling and habenular neurogenesis. A pharmacological block of melatonin receptors delays neurogenesis and reduces neuropil similarly to constant darkness, while addition of melatonin to embryos in constant darkness restores timely neurogenesis and neuropil. We conclude that light and melatonin schedule the differentiation of neurons and the formation of neural processes in the habenular nuclei.
| S-EPMC3171612 | biostudies-literature
Project description:Respiratory defensive behaviors, like coughing, play a crucial role in protecting the respiratory system, ensuring its integrity and optimal function. How these critical behaviors are regulated by sensory stimuli within the body remains largely unknown. Here, we show that the nucleus of the solitary tract (NTS) in mice, a key hub in the brain for processing internal sensory signals and mediating interoceptive processes, contains heterogenous neuronal populations that differentially control breathing. Within these subtypes, activation of tachykinin 1 (Tac1) neurons triggers a specific respiratory behavior. Our detailed characterization of respiratory defensive behaviors reveals that these responses are cough-like behaviors. Chemogenetic silencing or genetic ablation of Tac1 neurons significantly reduces cough-like behaviors induced by tussive challenges. These Tac1 neurons receive synaptic inputs from the bronchopulmonary chemosensory and mechanosensory neurons in the vagal ganglion, and directly integrate the medullary regions to control sequential phases of cough-like defensive behaviors. We propose that these Tac1 neurons are a key component of the airway-vagal-brain neural circuit that controls cough-like defensive behaviors in mice, and they coordinate the downstream modular circuits to elicit the sequential motor pattern of forceful expiratory responses.
2024-06-05 | GSE268741 | GEO
Project description:Heterogeneous ensembles are an effective approach in scenarios where the ideal data type and/or individual predictor are unclear for a given problem. These ensembles have shown promise for protein function prediction (PFP), but their ability to improve PFP at a large scale is unclear. The overall goal of this study is to critically assess this ability of a variety of heterogeneous ensemble methods across a multitude of functional terms, proteins and organisms. Our results show that these methods, especially Stacking using Logistic Regression, indeed produce more accurate predictions for a variety of Gene Ontology terms differing in size and specificity. To enable the application of these methods to other related problems, we have publicly shared the HPC-enabled code underlying this work as LargeGOPred ( https://github.com/GauravPandeyLab/LargeGOPred).
| S-EPMC6221071 | biostudies-literature
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:The nonapeptide, oxytocin (OT), known for its role in social bonding and attachment formation, has demonstrated anxiolytic properties in animal models and human studies. However, its role in the regulation of fear responses appears more complex, brain site-specific, sex-specific, and dependent on a prior stress history. Studies have shown that OT neurons in the hypothalamus are activated during cued and contextual fear conditioning and during fear recall, highlighting the recruitment of endogenous oxytocin system in fear learning. OT is released into the extended amygdala, which contains the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST), both critical for the regulation of fear and anxiety-like behaviors. Behavioral studies report that OT in the CeA reduces contextual fear responses; whereas in the BNST, OT receptor (OTR) neurotransmission facilitates cued fear and reduces fear responses to un-signaled, diffuse threats. These ostensibly contrasting behavioral effects support growing evidence that OT works to promote fear discrimination by reducing contextual fear or fear of diffuse threats, yet strengthening fear responses to imminent and predictable threats. Recent studies from the basolateral nucleus of the amygdala (BLA) support this notion and show that activation of OTR in the BLA facilitates fear discrimination by increasing fear responses to discrete cues. Also, OTR transmission in the CeA has been shown to mediate a switch from passive freezing to active escape behaviors in confrontation with an imminent, yet escapable threat but reduce reactivity to distant threats. Therefore, OT appears to increase the salience of relevant threat-signaling cues yet reduce fear responses to un-signaled, distant, or diffuse threats. Lastly, OTR signaling has been shown to underlie emotional discrimination between conspecifics during time of distress, social transmission of fear, and social buffering of fear. As OT has been shown to enhance salience of both positive and negative social experiences, it can also serve as a warning system against potential threats in social networks. Here, we extend the social salience hypothesis by proposing that OT enhances the salience of relevant environmental cues also in non-social contexts, and as such promotes active defensive behaviors.
| S-EPMC7538630 | biostudies-literature
Project description:The ventromedial hypothalamus (VMH) was thought to be essential for coping with threat, although its circuit mechanism remains unclear. To investigate this, we optogenetically activated steroidogenic factor 1 (SF1)-expressing neurons in the dorsomedial and central parts of the VMH (VMHdm/c), and observed a range of context-dependent somatomotor and autonomic responses resembling animals' natural defensive behaviors. By activating independent pathways emanating from the VMHdm/c, we demonstrated that VMHdm/c projection to the dorsolateral periaqueductal gray (dlPAG) induces inflexible immobility, while the VMHdm/c to anterior hypothalamic nucleus (AHN) pathway promotes avoidance. Consistent with the behavior changes induced by VMH to AHN pathway activation, direct activation of the AHN elicited avoidance and escape jumping, but not immobility. Retrograde tracing studies revealed that nearly 50% of PAG-projecting VMHdm/c neurons send collateral projection to the AHN and vice versa. Thus, VMHdm/c neurons employ a one-to-many wiring configuration to orchestrate multiple aspects of defensive behaviors.
| S-EPMC4368499 | biostudies-literature
Project description:Anatomic and physiologic studies have suggested a model in which neurons of the piriform cortex receive convergent input from random collections of glomeruli. In this model, odor representations can only be afforded behavioral significance upon experience. We have devised an experimental strategy that permits us to ask whether the activation of an arbitrarily chosen subpopulation of neurons in piriform cortex can elicit different behavioral responses dependent upon learning. Activation of a small subpopulation of piriform neurons expressing channelrhodopsin at multiple loci in the piriform cortex, when paired with reward or shock, elicits either appetitive or aversive behavior. Moreover, we demonstrate that different subpopulations of piriform neurons expressing ChR2 can be discriminated and independently entrained to elicit distinct behaviors. These observations demonstrate that the piriform cortex is sufficient to elicit learned behavioral outputs in the absence of sensory input. These data imply that the piriform does not use spatial order to map odorant identity or behavioral output.
| S-EPMC3230930 | biostudies-literature
Project description:The prefrontal cortex is an important regulator of fear expression in humans and rodents. Specifically, the rodent prelimbic (PL) prefrontal cortex drives fear expression during both encoding and retrieval of fear memory. Neuronal ensembles have been proposed to function as memory encoding units, and their re-activation is thought to be necessary for memory retrieval and expression of conditioned behavior. However, it remains unclear whether PL cortex neuronal ensembles that encode fear memory contribute to long-term fear expression during memory retrieval. To address this, we employed a viral-mediated TRAP (Targeted Recombination in Active Population) technology to target PL cortex ensembles active during fear conditioning and expressed the inhibitory Gi-DREADD in fear-encoding ensembles. Male and female rats were trained to lever press for food and subjected to Pavlovian delay fear conditioning, then 28 days later, they underwent a fear memory retrieval test. Chemogenetic inhibition of TRAPed PL cortex ensembles reduced conditioned suppression of food seeking in females, but not males. Neither context nor tone freezing behavior was altered by this manipulation during the same retrieval test. Thus, fear-encoding ensembles in PL cortex drive long-term fear expression in a sex and fear modality dependent manner.
| S-EPMC6656710 | biostudies-literature
Project description:The interplay of modern molecular simulation and high-quality nuclear magnetic resonance (NMR) experiments has reached a fruitful stage for quantitative characterization of structural ensembles of disordered peptides. Amyloid-? 1-42 (A?42), the primary peptide associated with Alzheimer's disease, and fragments such as A?21-30 are both classified as intrinsically disordered peptides (IDPs). We use a variety of NMR observables to validate de novo molecular dynamics simulations in explicit water to characterize the tertiary structure ensemble of A?42 and A?21-30 from the perspective of their classification as IDPs. Unlike the A?21-30 fragment that conforms to expectations of an IDP that is primarily extended, we find that A?42 samples conformations reflecting all possible secondary structure categories and spans the range of IDP classifications from collapsed structured states to highly extended conformations, making it an IDP with a far more heterogeneous tertiary ensemble.
| S-EPMC3474852 | biostudies-literature