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Functional organization of the hypothalamus. A. Sagittal view of a mouse brain. The hypothalamus (pink) is ventral to the thalamus (yellow), caudal to the bed nucleus of the stria terminalis (BST, gray), and includes the mammillary body (MB, red) at the boundary. Along the rostral-caudal axis, the hypothalamus is divided into 4 regions: the preoptic, the anterior, the posterior, and the mammillary regions. OX, optical chiasm. B. Schematic showing a fl attened view of the hypothalamus. The hypothalamus is divided into 3 columns that span the entire rostral-caudal length. During development, progenitors along the ventricles divide and migrate out in 3 consecutive waves. The fi rst wave (blue) populates the lateral column, the second wave (green) populates the medial column, and the third wave (orange) populates the periventricular column. The relative positions of major hypothalamic nuclei are indicated. PVN, paraventricular nucleus; SCN, suprachiasmatic nucleus; ARC, arcuate nucleus; POA, preoptic area; AH, anterior hypothalamus; DMH, dorsomedial hypothalamus; VMH, ventromedial hypothalamus; PMN, premammillary nucleus; VLPO, ventrolateral preoptic area; LH, lateral hypothalamus; TMN, tuberomammillary nucleus.
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Many complex behaviors that do not require learning are displayed and are termed innate. Although traditionally the subject matter of ethology, innate behaviors offer a unique entry point for neuroscientists to dissect the physiological mechanisms governing complex behaviors. Since the last century, converging evidence has implicated the hypothalam...
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Context 1
... hypothalamus lies beneath the thalamus at the ventral base of the brain. It is one of the most ancient brain structures and is highly conserved. It extends rostrally into the forebrain to the optic chiasm and caudally to include the mammillary body (Fig. 1A). Along the rostro- caudal axis, the hypothalamus is divided into four regions: the preoptic area, the anterior hypothalamus, the tuberal hypothalamus, and the mammillary body [4,5] . Within each region, a hypothalamic nucleus is identifi ed when there is an appearance of uniform cell groups. Such is the case for the paraventricular ...
Context 2
... development, progenitor cells along the ventricles divide in 3 consecutive waves and migrate outwards tangentially to populate the hypothalamus in a roughly "outside-in" manner (Fig. 1B). Based on these events, the hypothalamus is divided into 3 columns that span the entire rostro-caudal length: the periventricular, the medial, and the lateral columns [4,6] . These 3 columns appear to be functionally distinct but are extensively interconnected. Broadly speaking, the periventricular column projects to the anterior and ...
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Parental care is a limited resource which in many species is acquired by the offspring through begging behaviours and often causes competition between siblings. The Neotropical poison frog Ranitomeya variabilis provides a very specific form of parental care: because its tadpoles are cannibalistic males usually separate them from their siblings after...
Citations
... Most importantly, the neural circuits underlying individual innate behaviors, including sex, aggression, feeding, and sleep, have been well elucidated in recent years, making Drosophila an ideal model in which to study the mechanisms of decision-making among innate behaviors. Neural circuit mechanisms underlying individual innate behaviors have also been intensively studied in mice, with huge progress in the last two decades [1,[13][14][15][16][17][18]. Here, we review some of the latest progress on the neural circuits and neuromodulatory mechanisms of interaction among sex, fight, feeding, and sleep in both sexes of Drosophila, and compare the circuit configurations in flies and mice, aiming to provide new insights for understanding the neural mechanisms of action selection. ...
... Anderson has recently reviewed the functional similarity of the pC1 neurons in flies and the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) neurons in mice [3]. These neurons, like pC1 neurons in flies, integrate sex-related cues and social information to promote a scalable and persistent state and regulate both sexual and aggressive behaviors in mice [3,13,133]. The VMHvl neurons express sex pheromone receptors such as estrogen receptor 1 and/or progesterone receptor [3], similar to pC1 neurons expressing the sexdetermination genes fru and/or dsx. ...
Nervous systems must not only generate specific adaptive behaviors, such as reproduction, aggression, feeding, and sleep, but also select a single behavior for execution at any given time, depending on both internal states and external environmental conditions. Despite their tremendous biological importance, the neural mechanisms of action selection remain poorly understood. In the past decade, studies in the model animal Drosophila melanogaster have demonstrated valuable neural mechanisms underlying action selection of innate behaviors. In this review, we summarize circuit mechanisms with a particular focus on a small number of sexually dimorphic neurons in controlling action selection among sex, fight, feeding, and sleep behaviors in both sexes of flies. We also discuss potentially conserved circuit configurations and neuromodulation of action selection in both the fly and mouse models, aiming to provide insights into action selection and the sexually dimorphic prioritization of innate behaviors.
... Its structure and development are highly conserved among vertebrates [16,17]. The selective stimulation of hypothalamic circuits in the adult brain initiates a range of natural behaviours that are aimed to satisfy physiological and reproductive needs [2,[18][19][20][21][22][23]. Hypothalamic activity is critical for survival, both of the individual and of the species [24,25], through eating, drinking, thermoregulation, defensive behaviours, reproduction and rearing of young [2]. ...
We are curious by nature, particularly when young. Evolution has endowed our brain with an inbuilt obligation to educate itself. In this perspectives article, we posit that self-tuition is an evolved principle of vertebrate brain design that is reflected in its basic architecture and critical for its normal development. Self-tuition involves coordination between functionally distinct components of the brain, with one set of areas motivating exploration that leads to the experiences that train another set. We review key hypothalamic and telencephalic structures involved in this interplay, including their anatomical connections and placement within the segmental architecture of conserved forebrain circuits. We discuss the nature of educative behaviours motivated by the hypothalamus, innate stimulus biases, the relationship to survival in early life, and mechanisms by which telencephalic areas gradually accumulate knowledge. We argue that this aspect of brain function is of paramount importance for systems neuroscience, as it confers neural specialization and allows animals to attain far more sophisticated behaviours than would be possible through genetic mechanisms alone. Self-tuition is of particular importance in humans and other primates, whose large brains and complex social cognition rely critically on experience-based learning during a protracted childhood period.
This article is part of the theme issue ‘Systems neuroscience through the lens of evolutionary theory’.
... Beyond this, a more detailed dissection on the specific neural circuits that govern intraspecific aggression was not feasible until recent developments of sophisticated new tools that permit targeting and functional manipulation of genetically defined populations of neurons and their projections {reviewed in [23][24][25][26][27][28][29][30]}. As a result, we have witnessed an explosion of studies on neural mechanisms that govern intraspecific aggression in the model organism Mus musculus (house mouse) in the last 10 years. ...
... From the MeA and the BNST, conspecific male information is transmitted into the medial hypothalamic zone, where interconnected neurons control motivated behaviors related to reproduction [24,37,88]. Specifically, three hypothalamic nuclei along the anterior-posterior axis: the medial preoptic (mPOA), the ventrolateral division of the ventromedial hypothalamus (VMHvl), and the ventral division of the premammillary nuclei (PMv), reciprocally project to each other and regulate an array of reproductive behaviors including mating, parental care and intraspecific aggression in a sex-specific manner. ...
Individuals of many species fight with conspecifics to gain access to or defend critical resources essential for survival and reproduction. Such intraspecific fighting is evolutionarily selected for in a species-, sex-, and environment-dependent manner when the value of resources secured exceeds the cost of fighting. One such example is males fighting for chances to mate with females. Recent advances in new tools open up ways to dissect the detailed neural circuit mechanisms that govern intraspecific, particularly inter-male, aggression in the model organism Mus musculus (house mouse). By targeting and functional manipulating genetically defined populations of neurons and their projections, these studies reveal a core neural circuit that controls the display of reactive male–male attacks in mice, from sensory detection to decision making and action selection. Here, we summarize these critical results. We then describe various modulatory inputs that route into the core circuit to afford state-dependent and top–down modulation of inter-male attacks. While reviewing these exciting developments, we note that how the inter-male attack circuit converges or diverges with neural circuits that mediate other forms of social interactions remain not fully understood. Finally, we emphasize the importance of combining circuit, pharmacological, and genetic analysis when studying the neural control of aggression in the future.
... For more than a century, research had been ongoing. Af-ter much research, the academic community has produced some theories, such as the oxidative stress theory [2], the inflammatory factor theory [3,4], and the cholinergic nerve loss theory [5,6]. The pathogenesis of AD is still controversial, but no matter which mechanism plays a role in the occurrence and development of AD, the typical histopathological changes include β-amyloid (Aβ) deposition, neurofibrillary tangles formed by hyper-phosphorylation of tau protein, and extensive neuronal loss. ...
Objective:
Vitamin D (Vit D), a steroid hormone, has been linked to cognitive impairment and dementia, such as Alz-heimer's disease (AD). 1, 25(OH)2D3 is the biologically active form of Vit D, which has been shown to have neuroprotective effects. This compound is being evaluated as an emerging therapeutic treatment in models of AD.
Material and methods:
The present study was designed to investigate whether Vit D could alleviate cognitive impairment in an AD rat model by regulating the VDR/ERK1/2 signaling pathway. Adult male APPswe/PS1ΔE9 rats (n = 40) were randomly divided into 2 groups: the AD group and the Vit D + AD group (20 mice per group), and 40 C57BL/6J age-matched mice were separated into the control (CON) group and the Vit D + CON group (20 mice per group). The Morris water maze and object recognition tests were used to evaluate learning and memory functions of the mice. Hematoxylin and eosin staining was used to evaluate morphological changes in hippocampal neurons. Western blotting was used to evaluate the proteins responsible for these changes.
Results:
We found that Vit D improved learning and memory abilities and morphological defects in hippocampal neurons. Vit D decreased the gene expression of caspase-3 and Bax and increased the expression of Bcl-2. Vit D also increased the protein expression of VDR and p-ERK1 protein in AD mice.
Conclusion:
This study provides new clues about the mechanism by which Vit D exerts neuroprotective effects in an AD mouse model.
... The medial preoptic area (mPOA) of the hypothalamus functions as an essential node in an evolutionarily-conserved neural network that controls social behaviors [1][2][3]. Notably, it is sexually dimorphic in nearly all species examined to date [4][5][6][7], including humans [8,9]. Sexually dimorphic features of the mPOA include neuronal number/density [10,11], synaptic organization [12], distribution of innervating fibers [13], and gene expression levels [14]. ...
Despite extensive characterization of sex differences in the medial preoptic area (mPOA) of the hypothalamus, we know surprisingly little about whether or how male and female mPOA neurons differ electrophysiologically, especially in terms of neuronal firing and behavioral pattern generation. In this study, by performing whole-cell patch clamp recordings of the mPOA, we investigated the influences of sex, cell type, and gonadal hormones on the electrophysiological properties of mPOA neurons. Notably, we uncovered significant sex differences in input resistance (male > female) and in the percentage of neurons that displayed post-inhibitory rebound (male > female). Furthermore, we found that the current mediated by the T-type Ca2+ channel (IT), which is known to underlie post-inhibitory rebound, was indeed larger in male mPOA neurons. Thus, we have identified salient electrophysiological properties of mPOA neurons, namely IT and post-inhibitory rebound, that are male-biased and likely contribute to the sexually dimorphic display of behaviors.
... Behavior can roughly be divided into innate and learned behaviors. Innate behavior is often species-specific, stable over time and between individuals and, from first performance, the full behavioral complex is present and functional (Zha and Xu, 2015). Innate behavior often has a direct survival value for the individual or species, e.g. ...
... Innate behavior often has a direct survival value for the individual or species, e.g. feeding, aggression and parental care, and is sometimes referred to as instinct or instinctive behaviors (Zha and Xu, 2015). Learned behaviors develop over time in the individual under the influence of the environment. ...
Digital archive: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-405313
Adolescence is an important developmental phase with large changes in behavior, physiology and neurobiology, which transform an individual from immature child to independent adult. Due to these changes, adolescence is a sensitive period for exposure to environmental factors such as stress and drug exposure; it is also a common age of onset for alcohol consumption as well as several psychiatric disorders. Despite these factors, less is known about this developmental period than regarding adult individuals. Behavior is regulated by the central nervous system and can be used as a lens to study these processes as well as for examination of associations between individual differences, early-life stress and alcohol. The aim of this thesis was to experimentally examine adolescent behavior and its links to early-life stress and alcohol in adolescent male and female rats. Different behavioral tests were used to profile adolescent animals together with animal models of early-life stress, voluntary alcohol consumption and alcohol exposure. In addition, stress responsiveness after early-life stress and the impact of alcohol exposure on endogenous opioid peptide levels as well as blood alcohol concentrations were examined. The adolescent behavioral profile in the multivariate concentric square field™ (MCSF) was characterized and validated against the elevated plus maze and open field tests. The main finding was subgroups based on individual variation that revealed three distinct behavioral types: Explorers, Shelter seekers and Main type animals. This pattern was replicated in an additional, independent cohort. Early-life stress, modelled by prolonged maternal separation, showed small effects on behavior in the MCSF and on social play behavior. However, an effect on stress responsiveness in males but not females subjected to prolonged maternal separation was discovered. Predisposition for high alcohol consumption did not have a shared behavioral profile among selectively bred rat lines. However, a subgroup of high drinking individuals in an outbred cohort showed behavioral similarities to one of the selectively bred lines. Alcohol exposure showed small, but sex-dependent, effects on behavior and endogenous opioid peptide levels. Together, these studies provide new information about adolescent behavior and associations to early-life stress and alcohol in males and females, relationships not extensively studied in adolescence.
... The hypothalamus controls numerous homeostatically regulated behaviors that are known to differ between surface fish and cavefish, including sleep, feeding, stress, and social behaviors (Duboué et al., 2011;Kowalko et al., 2013a,b;Chin et al., 2018;Lloyd et al., 2018;Zha and Xu, 2015). To determine whether these behavioral changes are accompanied by alterations in anatomy, we quantified the overall size of the hypothalamus, as well as individual subnuclei that modulate distinct behaviors in mammals ( Figure 5 and Supplementary Figure S3). ...
A shift in environmental conditions impacts the evolution of complex developmental and behavioral traits. The Mexican cavefish, Astyanax mexicanus, is a powerful model for examining the evolution of development, physiology, and behavior because multiple cavefish populations can be compared to an extant, ancestral-like surface population of the same species. Many behaviors have diverged in cave populations of A. mexicanus, and previous studies have shown that cavefish have a loss of sleep, reduced stress, an absence of social behaviors, and hyperphagia. Despite these findings, surprisingly little is known about the changes in neuroanatomy that underlie these behavioral phenotypes. Here, we use serial sectioning to generate brain atlases of surface fish and three independent cavefish populations. Volumetric reconstruction of serial-sectioned brains confirms convergent evolution on reduced optic tectum volume in all cavefish populations tested. In addition, we quantified volumes of specific neuroanatomical loci within several brain regions that have previously been implicated in behavioral regulation, including the hypothalamus, thalamus, and habenula. These analyses reveal an enlargement of the hypothalamus in all cavefish populations relative to surface fish, as well as subnuclei-specific differences within the thalamus and prethalamus. Taken together, these analyses support the notion that changes in environmental conditions are accompanied by neuroanatomical changes in brain structures associated with behavior. This atlas provides a resource for comparative neuroanatomy of additional brain regions and the opportunity to associate brain anatomy with evolved changes in behavior.
... In line with our results, recent reports indicate that feeding behavior is controlled by a closely interactive network involving the hypothalamus, brainstem, and limbic system (Jennings et al., 2013;Sternson and Eiselt, 2017;Zha and Xu, 2015). The observations that BNST cells separately project to the anterior vlPAG and LH and that both pathways contribute to feeding behavior suggests that, in addition to the LH and BNST, the anterior vlPAG may also be a key node in the feeding circuitry. ...
Graphical Abstract Highlights d Inhibition of anterior vlPAG GABAergic cell activity induces feeding behavior d Activation of these cells reduces food intake in starving mice d Long-term manipulations elicit a corresponding change in mouse body weight d The BNST and LH regulate feeding via long GABAergic projections to the vlPAG In Brief Hao et al. uncovered an important role of the GABAergic cells in the anterior ventrolateral periaqueductal gray (vlPAG) and two distinct midbrain GABAergic pathways (the lateral hypothalamus-vlPAG and BNST-vlPAG) in regulation of feeding behavior.
... In line with our results, recent reports indicate that feeding behavior is controlled by a closely interactive network involving the hypothalamus, brainstem, and limbic system (Jennings et al., 2013;Sternson and Eiselt, 2017;Zha and Xu, 2015). The observations that BNST cells separately project to the anterior vlPAG and LH and that both pathways contribute to feeding behavior suggests that, in addition to the LH and BNST, the anterior vlPAG may also be a key node in the feeding circuitry. ...
Overeating is a serious issue in modern society, causing many health problems, including obesity. Although the hypothalamus has been previously identified as the key brain structure that regulates body weight homeostasis, the downstream pathways and non-canonical neural circuitry involved in feeding behavior remain largely uncharacterized. Here, we discover that suppressing the activity of GABAergic cells in the anterior ventrolateral periaqueductal gray (vlPAG), whether directly or through long-projection GABAergic inputs from either the bed nucleus of the stria terminalis (BNST) or the lateral hypothalamus (LH), is sufficient to promptly induce feeding behavior in well-fed mice. In contrast, optogenetic activation of these cells interrupts food intake in starved mice. Long-term chemogenetic manipulation of vlPAG GABAergic cell activity elicits a corresponding change in mouse body weight. Our studies reveal distinct midbrain GABAergic pathways and highlight an important role of GABAergic cells in the anterior vlPAG in feeding behavior.
... The mPOA is a key node in a conserved neural network that controls social behaviors and is activated during social interactions [43,[53][54][55][56]. Therefore, it is well-positioned to detect female cues and drive USV production. ...
Adult male mice emit highly complex ultrasonic vocalizations (USVs) in response to female conspecifics. Such USVs, thought to facilitate courtship behaviors, are routinely measured as a behavioral index in mouse models of neurodevelopmental and psychiatric disorders such as autism. While the regulation of USVs by genetic factors has been extensively characterized, the neural mechanisms that control USV production remain largely unknown. Here, we report that optogenetic activation of the medial preoptic area (mPOA) elicited the production of USVs that were acoustically similar to courtship USVs in adult mice. Moreover, mPOA vesicular GABA transporter-positive (Vgat +) neurons were more effective at driving USV production than vesicular glutamate transporter 2-positive neurons. Furthermore, ablation of mPOA Vgat+ neurons resulted in altered spectral features and syllable usage of USVs in targeted males. Together, these results demonstrate that the mPOA plays a crucial role in modulating courtship USVs and this may serve as an entry point for future dissection of the neural circuitry underlying USV production.
