Anterior Hypothalamic Nucleus Research Articles

Genetic Isolation of Hypothalamic Neurons that Regulate Context-Specific Male Social Behavior.

Nearly all animals engage in a complex assortment of social behaviors that are essential for the survival of the species. In mammals, these behaviors are regulated by sub-nuclei within the hypothalamus, but the specific cell types within these nuclei responsible for coordinating behavior in distinct contexts are only beginning to be resolved. Here, we identify a population of neurons in the ventral premammillary nucleus of the hypothalamus (PMV) that are strongly activated in male intruder mice in response to a larger resident male but that are not responsive to females. Using a combination of molecular and genetic approaches, we demonstrate that these PMV neurons regulate intruder-specific male social behavior and social novelty recognition in a manner dependent on synaptic release of the excitatory neurotransmitter glutamate. These data provide direct evidence for a unique population of neurons that regulate social behaviors in specific contexts.

The differential mice response to cat and snake odor

Studies from the last two decades have pointed to multiple mechanisms of fear. For responding to predators, there is a group of highly interconnected hypothalamic nuclei formed by the anterior hypothalamic nucleus, the ventromedial hypothalamic nucleus and the dorsal premammillary nucleus — the predator-responsive hypothalamic circuit. This circuit expresses Fos in response to predator presence or its odor. Lesion of any component of this system blocks or reduces the expression of fear and consequently defensive behavior when faced with a predator or its cue. However, most of the knowledge about that circuit has been obtained using the rat as a model of prey and the cat as a source of predator cues. In the present study, we exposed mice to strong cat or snake odors, two known mice predators, and then we used the rat exposure test (RET) to study their behavior when confronted with the same predator's odor. Our data point to a differential response of mice exposed to these odors. When Swiss mice were exposed to the cat odor, they show defensive behavior and the predator-responsive hypothalamic circuit expressed Fos. The opposite was seen when they faced snake's odor. The acute odor exposure was not sufficient to activate the mouse predator-responsive hypothalamic circuit and the mice acted like they were not in a stressful situation, showing almost no sign of fear or defensive posture. This leads us to the conclusion that not all the predator cues are sufficient to activate the predator-responsive hypothalamic circuit of mice and that their response depends on the danger that these predators represent in the natural history of the prey.

Collateral Pathways from the Ventromedial Hypothalamus Mediate Defensive Behaviors

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.

P.5.c.004 The influence of hypothalamic proline-rich polypeptide-1 on stem cell maintenance in hippocampus of amyloid-exposed rats

The present study is an examination, using an indirect immunofluorescence method, of the distribution of visinin, a 24,000 dalton peptide, in the rat forebrain and diencephalon.Immunoreactive structures were localized in the neuronal elements showing an uneven distribution. Immunoreactive neurons were found in the olfactory bulb, anterior olfactory nucleus, cerebral cortex, amygdaloid complex, ventral portion of the nucleus caudatus putamen, septal area, nucleus accumbens, nucleus paratenialis, nucleus rhomboideus, nucleus reuniens, nucleus paraventricularis hypothalami, nucleus supraopticus, nucleus anterior hypothalami, preoptic area, hypothalamic periventricular nucleus, nucleus mammillaris medialis, medial habenular nucleus, zona incerta. nucleus lateralis thalami, nucleus tractus optici and gyrus dentatus.Immunoreactive fibers were observed in the above areas, particularly near the labelled cells, forming fiber plexuses of varying density. In addition, dense plexuses were also seen in the globus pallidus, anteroventral nucleus of the thalamus, substantia nigra and hippocampus. In the former three structures, no labelled cells were present and in the latter, a few scattered neurons were found, indicating that these fibers originate from extrinsic sources.

Hypothalamic orexin-A (hypocretin-1) neuronal projections to the vestibular complex and cerebellum in the rat

Immunohistochemistry combined with retrograde tract-tracing techniques were used to investigate the distribution of orexin-A (OX-A)- and OX-A receptor-like (OX1) immunoreactivity within the vestibular complex and cerebellum, and the location of hypothalamic OX-A neurons sending axonal projections to these regions in the Wistar rat. OX-A immunoreactive fibers and presumptive terminals were found throughout the medial (MVe) and lateral (LVe) vestibular nuclei. Light fiber labeling was also observed in the spinal and superior vestibular nuclei. Within the cerebellum, dense fiber and presumptive terminal labeling was observed in the medial cerebellar nucleus (Med; fastigial nucleus), with less dense labeling in the interposed (Int) and lateral cerebellar nuclei (Lat; dentate nucleus). A few scattered OX-A immunoreactive fibers were also observed throughout the cortex of the paraflocculus. OX1-like immunoreactivity was found densely concentrated within LVe, moderate in MVe, and scattered within the spinal and superior vestibular nuclei. Within the cerebellum, OX1-like immunoreactivity was also observed densely within Med and in the dorsolateral aspects of Int. Additionally, OX1 like-labeling was found in Lat, and within the granular layer of the caudal paraflocculus cerebellar cortex. Fluorogold (FG) microinjected into these vestibular and cerebellar regions resulted in retrogradely labeled neurons throughout the ipsilateral hypothalamus. Retrogradely labeled neurons containing OX-A like immunoreactivity were observed dorsal and caudal to the anterior hypothalamic nucleus and extending laterally into the lateral hypothalamic area, with the largest number clustered around the dorsal aspects of the fornix in the perifornical area. A few FG OX-A like-immunoreactive neurons were also observed scattered throughout the dorsomedial, and posterior hypothalamic nuclei. These data indicate that axons from OX-A neurons terminate within the vestibular complex and deep cerebellar nuclei of the cerebellum and although the function of these pathways is unknown, they likely represent pathways by which hypothalamic OX-A containing neurons co-ordinate vestibulo-cerebellar motor and autonomic functions associated with ingestive behaviors.

Inducible neuronal inactivation of Sim1 in adult mice causes hyperphagic obesity.

Germline haploinsufficiency of human or mouse Sim1 is associated with hyperphagic obesity. Sim1 encodes a transcription factor required for proper formation of the paraventricular (PVN), supraoptic, and anterior periventricular hypothalamic nuclei. Sim1 expression persists in these neurons in adult mice, raising the question of whether it plays a physiologic role in regulation of energy balance. We previously showed that Sim1 heterozygous mice had normal numbers of PVN neurons that were hyporesponsive to melanocortin 4 receptor agonism and showed reduced oxytocin expression. Furthermore, conditional postnatal neuronal inactivation of Sim1 also caused hyperphagic obesity and decreased hypothalamic oxytocin expression. PVN projections to the hindbrain, where oxytocin is thought to act to modulate satiety, were anatomically intact in both Sim1 heterozygous and conditional knockout mice. These experiments provided evidence that Sim1 functions in energy balance apart from its role in hypothalamic development but did not rule out effects of Sim1 deficiency on postnatal hypothalamic maturation. To address this possibility, we used a tamoxifen-inducible, neural-specific Cre transgene to conditionally inactivate Sim1 in adult mice with mature hypothalamic circuitry. Induced Sim1 inactivation caused increased food and water intake and decreased expression of PVN neuropeptides, especially oxytocin and vasopressin, with no change in energy expenditure. Sim1 expression was not required for survival of PVN neurons. The results corroborate previous evidence that Sim1 acts physiologically as well as developmentally to regulate body weight. Inducible knockout mice provide a system for studying Sim1's physiologic function in energy balance and identifying its relevant transcriptional targets in the hypothalamus.

Circadian Cycle and Adolescentss Nonverbal Intelligence

‘Circadian Cycle’, the biological clock within the organism, is the cyclic changes in bodily process occurring within a single day basing on our conscious awareness which is generated endogenously by the anterior hypothalamic suprachiasmatic nuclei and modulated by exogenous factors. In other words, the state of activity and arousal level in the series of different cycles of sleep and wakefulness, in most of the cases, is generated, controlled, guided, and explained in terms of Circadian Cycle. This activating level of the mind has its origin from the very childhood stage of the organism and reaches its peak in adolescence, basing on different ecological, anthropological, sociological, and psychological points of view. An investigation was made on the effect of circadian cycle on the intelligence level of 100 urban and 100 tribal school children (age 10-14 of class IV and class VI) of Nayagarh District, different Govt. schools, ‘Sai Saraswati Sishumandiir School’, and from the KISS School of KIIT University, Bhubaneswar, Odisha. After being randomly selected the subjects were individually administered the Raven’s Advanced progressive matrices tests of intelligence in their natural environment. All of them were tested for four times a day: in morning, noon, evening and night; and accordingly their IQ scores were recorded. The analysis of results revealed that irrespective of culture, the IQ of the subjects was differentially affected by varying degrees of circadian cycles. It was more in noon than evening and morning and more in morning than night. The difference in intelligence scores between urban and tribal children, analyzed by Two Way ANOVA, was found to be statistically significant. The interaction of circadian cycle and culture was also found to have highly significant effect on intelligence scores of the subject. The most interesting part of the findings was, in night shifts, tribal adolescents were more active than their urban counterparts indicating their ecological and anthropological stand point of circadian cycle (t=3.62). The means of the intelligence scores of urban and tribal children were 9.81 (SD=1.62) and 9.56 (SD=1.75) respectively. This group difference was found to be statistically significant. In other words both urban and tribal children are more or less not equal with regard to their intelligence scores. The means of the intelligence scores of the subjects , at morning , noon , evening and night, irrespective of socio-cultural groups were 8.29 (SD=1.76), 11.59 (SD=1.72), 10.31 (SD=1.66) and 8.57 (SD=1.62), respectively. This mean difference was found to be statistically significant. In other words Circadian Rhythms have significant effects on the intelligence score of the subjects. More important is subsequent Newmann-Keuls post hoc test revealed significant differences among all possible group comparisons in favor of noon shift.

Inner capillary diameter of hypothalamic paraventricular nucleus of female rat increases during lactation

BackgroundThe role of the endothelial cell (EC) in blood flow regulation within the central nervous system has been little studied. Here, we explored EC participation in morphological changes of the anterior hypothalamic paraventricular nucleus (PVN) microvasculature of female rats at two reproductive stages with different metabolic demand (virginity and lactation). We measured the inner capillary diameter (ICD) of 800 capillaries from either the magnocellular or parvocellular regions. The space occupied by neural (somas, dendrites and axons) and glial, but excluding vascular elements of the neurovascular compartment was also measured in 100-μm2 sample fields of both PVN subdivisions.ResultsThe PVN of both groups of animals showed ICDs that ranged from 3 to 10 microns. The virgin group presented mostly capillaries with small ICD, whereas the lactating females exhibited a significant increment in the percentage of capillaries with larger ICD. The space occupied by the neural and glial elements of the neurovascular compartment did not show changes with lactation.ConclusionsOur findings suggest that during lactation the microvasculature of the PVN of female rats undergoes dynamic, transitory changes in blood flow as represented by an increment in the ICD through a self-cytoplasmic volume modification reflected by EC changes. A model of this process is proposed.

C-Fos immunoreactivity of neural cells in intoxication due to high-dose methamphetamine

Methamphetamine (METH) is a powerful and toxic psychostimulant that is abused worldwide. Although many studies of its toxic functions have been done on animals and humans, the mechanism is still poorly understood. In addition, the doses of METH examined have often been low. Here, we investigated the effects of intoxication due to administration of 20 mg/kg METH on neuronal activity. The mice showed hyperthermia and stereotyped behavior during 60 min after injection. We examined plasma stress hormone levels, which indicated that exposure to METH stimulated the hypothalamic-pituitary-adrenal (HPA) axis and caused release of stress hormones soon after injection. The maximum levels of adrenocorticotropic hormone and corticosterone occurred 10 and 60 min, respectively, after injection. We examined c-Fosprotein in 16 different brain regions at 60 min post injection to identify potential brain regions subject to the stimulant effect. Nine regions, including the anterior hypothalamic area, medial preoptic area, lateral hypothalamic area, paraventricular thalamic nucleus, lateral anterior hypothalamic nucleus, lateral septum, striatum, nucleus accumbens, and amygdala, showed a significant increase in c-Fos expression, while the other seven regions did not. These results indicate that responsive neurons in the regions containing c-Fos immunoreactivity (Fos-IR) may undergo cellular reaction to high-dose METH administration. The present study provides support for a relationship among hyperthermia, the HPA axis and neuronal activities in limited brain regions on exposure to 20 mg/kg METH.

Altered expression of FosB/ΔFosB in central autonomic regions in hypertensive obese Zucker rats

Adult obese Zucker rats (OZR) have elevated sympathetic nerve activity and blood pressure vs. lean Zucker rats (LZR). We determined whether autonomic regulatory regions in the brain are chronically activated in OZR vs. LZR by immunohistochemical examination of FosB/ΔFosB expression. Male rats (14 wks) were perfused with paraformaldehyde and brains were sectioned coronally. One in six sections were processed for FosB expression (Santa Cruz goat anti‐FosB) via a nickel diaminobenzidine (DAB) reaction. A subset was processed to reveal catecholaminergic neurons (Chemicon mouse anti‐tyrosine hydroxylase) via a DAB reaction. In nucleus tractus solitarius (−13.1 to −13.5 mm bregma) FosB expression was higher (85–134%) in OZR (7) vs. LZR (6) at all levels. In rostral ventrolateral medulla (−12.0 to −12.6 mm bregma) FosB expression was enhanced at the most caudal level (−12.6 mm) in OZR with comparable expression in other levels in OZR (5) vs. LZR (5). In NTS and RVLM there was no FosB expression in catecholaminergic neurons in OZR or LZR. In the hypothalamic paraventricular nucleus (PVN) OZR (5) had less FosB expression (94–200%) vs. LZR (5). Similarly, in the anterior hypothalamic nucleus OZR(6) had less (18–44%) expression than LZR(6). These data suggest that the chronic activations of multiple autonomic regions are altered in OZR vs. LZR, and future studies are needed to identify the phenotypes of the activated neurons.

Presence of prolactin mRNA in extra-pituitary brain areas in the domestic turkey

It is well known that prolactin plays diverse roles in vertebrate reproduction. Besides expression in the pituitary, prolactin is also found in extra-pituitary tissues. In the present study, prolactin mRNA expression was studied utilizing in situ hybridization histochemistry. Prolactin mRNA, while found throughout the turkey brain, was predominantly localized within the pituitary, confirming a pivotal role of prolactin in turkey reproduction. The expression of prolactin mRNA was also observed within extra-pituitary brain areas including the cerebellum, nucleus accumbens, lateral septum, anterior hypothalamic nucleus, lateral hypothalamus, paraventricular nucleus, ventromedial nucleus, and infundibular nuclear complex. In the hypothalamus, an abundance of prolactin mRNA-expressing cells was observed in the anterior hypothalamic nucleus, lateral hypothalamus, and ventromedial nucleus. Cells expressing the least prolactin mRNA were found in the lateral septum, paraventricular nucleus, and the infundibular nuclear complex. This study reveals, for the first time, that prolactin mRNA was expressed in extra-pituitary brain areas in birds. In addition, the diverse expression of prolactin mRNA in the brain areas suggests that prolactin plays various physiological roles in birds.

Short photoperiods alter cannabinoid receptor expression in hypothalamic nuclei related to energy balance

This study examined the photoperiodic regulation of energy balance and cannabinoid receptor expression in the Siberian hamster ( Phodopus sungorus) hypothalamus. Short day lengths, beginning at weaning, reduced food intake, body mass and fat pad masses and also decreased cannabinoid receptor immunostaining in the anterior and lateral hypothalamic nuclei of male hamsters. These data suggest a potential role for reduced cannabinoid drive in mediating short day-induced alterations in energy balance.

GABAergic mechanisms of anterior and ventromedial hypothalamic nuclei in the expression of freezing in response to a light-conditioned stimulus.

The amygdala, dorsal periaqueductal gray (dPAG), and medial hypothalamus have long been recognized to comprise a neural system responsible for the generation and elaboration of unconditioned fear in the brain. This neural substrate is well known to be under tonic inhibitory control exerted by γ-aminobutyric acid (GABA) mechanisms. Some evidence also suggests that these structures integrate conditioned fear. A recent study using the fear-potentiated startle paradigm showed that GABAergic mechanisms in the anterior hypothalamic nucleus (AHN) and dorsomedial part of the ventromedial hypothalamic nucleus (VMHDM) regulate conditioned fear. The present study examined the extent to which GABAergic mechanisms in these brain regions are involved in conditioned fear by measuring freezing in response to a light used as a conditioned stimulus (CS). The GABAA receptor agonist muscimol and the GABA-synthesizing enzyme glutamic acid decarboxylase inhibitor semicarbazide were used as an enhancer and inhibitor of GABA mechanisms, respectively. Muscimol and semicarbazide were injected into the AHN or VMHDM of rats before fear conditioning. Muscimol injections into the AHN and VMHDM significantly reduced conditioned freezing, whereas inhibition of GABA transmission increased this conditioned response in the AHN. The present study further supports the hypothesis that GABAergic mechanisms in the AHN and VMHDM exert inhibitory control on the neural substrates of conditioned fear in the hypothalamus.

Distribution of orexinergic neurons and their terminal networks in the brains of two species of African mole rats

The distribution of orexinergic cell bodies and terminal networks within the brains of two species of African mole rat (Cape-dune mole rat – Bathyergus suillus and highveld mole rat – Cryptomys hottentotus) were identified using immunohistochemistry for orexin-A. The aim of the study was to investigate possible differences in the nuclear complement and terminal distribution of this system by comparing those of the mole rats to published studies of other rodents and mammals. The wild-caught mole rats used in this study live a subterranean lifestyle and are well known for their regressed visual system, which may lead to the prediction of differences in the distribution of the cell bodies and the terminal networks; however, we found that both species of mole rat displayed orexinergic nuclei limited to the hypothalamus in regions similar to those previously reported for other rodent and mammalian species. No immunoreactive neurons could be identified, in either species of mole rat within the anterior hypothalamic paraventricular nucleus, as has been reported for Murid rodents. The terminal networks, while remaining similar between the species, are more strongly expressed in the Cape-dune mole rat than in the highveld mole rat.

Functional Networks in the Anesthetized Rat Brain Revealed by Independent Component Analysis of Resting-State fMRI

The rodent brain is organized into functional networks that can be studied through examination of synchronized low-frequency spontaneous fluctuations (LFFs) of the functional magnetic resonance imaging -blood-oxygen-level-dependent (BOLD) signal. In this study, resting networks of LFFs were estimated from the whole-brain BOLD signals using independent component analysis (ICA). ICA provides a hypothesis-free technique for determining the functional connectivity map that does not require a priori selection of a seed region. Twenty Long-Evans rats were anesthetized with isoflurane (1%, n = 10) or ketamine/xylazine (50/6 mg . kg(-1) . h(-1) ip, n = 10) and imaged for 5-10 min in a 9.4 T MR scanner without experimental stimulation or task requirement. Independent, synchronous LFFs of BOLD signals were found to exist in clustered, bilaterally symmetric regions of both cortical and subcortical structures, including primary and secondary somatosensory cortices, motor cortices, visual cortices, posterior and anterior cingulate cortices, hippocampi, caudate-putamen, and thalamic and hypothalamic nuclei. The somatosensory and motor cortices typically demonstrated both symmetric and asymmetric components with unique frequency profiles. Similar independent network components were found under isoflurane and ketamine/xylazine anesthesia. The report demonstrates, for the first time, 12 independent resting networks that are bilaterally synchronous in different cortical and subcortical areas of the rat brain.

Identification, Localization, and Function of a Novel Avian Hypothalamic Neuropeptide, 26RFa, and Its Cognate Receptor, G Protein-Coupled Receptor-103

Several neuropeptides with the C-terminal RFamide sequence have been identified in the hypothalamus of a variety of vertebrates. Among the RFamide peptide groups, however, only LPXRFamide peptides, including gonadotropin-inhibitory hormone, have been characterized in the avian brain. In the present study, we sought for the presence of other RFamide peptides in the avian hypothalamus. We identified a cDNA encoding an RFamide peptide orthologous to 26RFa (also referred to as QRFP) in the hypothalamus of the Japanese quail. The deduced quail 26RFa precursor consisted of 120-amino-acid residues, encoding one RFamide peptide with 27 amino acids. This RFamide peptide was flanked at the N terminus by a dibasic amino acid cleavage site and at the C terminus by a glycine amidation signal. Quantitative RT-PCR analysis demonstrated specific expression of quail 26RFa mRNA in the diencephalon including the hypothalamus. Furthermore, mass spectrometry analysis revealed the presence of a peptide exhibiting the mass of mature 26RFa, indicating that the peptide is actually produced from the precursor in the diencephalon. 26RFa-producing cell bodies were localized in the anterior hypothalamic nucleus in the brain. Synthetic 26RFa increased intracellular Ca(2+) concentration in HEK293T cells transfected with the chicken G protein-coupled receptor GPR103. Intracerebroventricular injection of 26RFa in broiler chicks stimulated feeding behavior. These data provide the first evidence for the occurrence of the peptide 26RFa in the avian hypothalamus and indicate that this peptide exerts orexigenic activity.

Morphology and distribution of neurons expressing serotonin 5-HT 1A receptors in the rat hypothalamus and the surrounding diencephalic and telencephalic areas

Disorders of serotonergic neurotransmission are involved in disturbances of numerous hypothalamic functions including circadian rhythm, mood, neuroendocrine functions, sleep and feeding. Among the serotonin receptors currently recognized, 5-HT 1A receptors have received considerable attention due to their importance in the etiology of mood disorders. While previous studies have shown the presence of 5-HT 1A receptors in several regions of the rat brain, there is no detailed map of the cellular distribution of 5-HT 1A receptors in the rat diencephalon. In order to characterize the distribution and morphology of the neurons containing 5-HT 1A receptors in the diencephalon and the adjacent telencephalic areas, single label immunohistochemistry was utilized. Large, multipolar, 5-HT 1A-immunoreactive (IR) neurons were mainly detected in the magnocellular preoptic nucleus and in the nucleus of diagonal band of Broca, while the supraoptic nucleus contained mainly fusiform neurons. Medium-sized 5-HT 1A-IR neurons with triangular or round-shaped somata were widely distributed in the diencephalon, populating the zona incerta, lateral hypothalamic area, anterior hypothalamic nucleus, substantia innominata, dorsomedial and premamillary nuclei, paraventricular nucleus and bed nucleus of stria terminalis. The present study provides schematic mapping of 5-HT 1A-IR neurons in the rat diencephalon. In addition, the morphology of the detected 5-HT 1A-IR neural elements is also described. Since rat is a widely used laboratory animal in pharmacological models of altered serotoninergic neurotransmission, detailed mapping of 5-HT 1A-IR structures is pivotal for the neurochemical characterization of the neurons containing 5-HT 1A receptors.

Long-lasting FosB/ΔFosB immunoreactivity in the rat brain after repeated cat odor exposure

Cat odor elicits defensive responses in rats that are modified by repeated exposure to the odor. We explored the neural correlates of this adaptation using FosB/ΔFosB immunohistochemistry. Rats were given 3 × 60 min exposures to either a worn cat collar (repeated cat odor group) or unworn cat collar (control group). Each exposure was separated by 48 h. Rats exposed to cat odor initially showed strong defensive responses (decreased contact, increased retreat, and increased fecal pellets), however these responses had habituated by the final exposure. Rats were perfused 24 h or 7 days after the final exposure and the brains were processed for FosB/ΔFosB protein expression. Up-regulation of FosB/ΔFosB was observed 24 h after repeated cat odor exposure in the nucleus accumbens core, caudate putamen, ventrolateral periaqueductal gray, and four hypothalamic regions: lateral hypothalamus, ventromedial hypothalamus, anterior hypothalamic nucleus, and dorsal premammillary nucleus. FosB/ΔFosB expression remained elevated 7 days after repeated cat odor exposure in the nucleus accumbens core, caudate putamen and anterior hypothalamic nucleus. These findings provide initial evidence that behavioral changes occurring as a result of repeated predatory stress are associated with long-lasting regionally specific neuroadaptations in the brain.

The medial hypothalamic defensive circuit and 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) induced fear: Comparison of electrolytic and neurotoxic lesions

The neural circuits for unconditioned fear to predator odors (e.g., cat fur odor, trimethylthiazoline, TMT) are not well delineated. A putative neural circuit for predator odor fear, the medial hypothalamic defensive circuit (MHDC), consisting of the anterior hypothalamic (AHN), ventromedial hypothalamic (VMH) and dorsal premammillary nuclei (PMd), has been proposed. Electrolytic and ibotenic acid lesions of the PMd have been shown to reduce unconditioned fear in rats presented with either a cat or cat odor. Whether the PMd, AHN and VMH are involved in unconditioned fear to another predator odor derived from fox feces, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), has not been explored. The present study compared the effects of electrolytic and neurotoxic lesions of MHDC nuclei in rats on unconditioned fear to TMT and shock-induced contextually conditioned fear, as measured by freezing. Electrolytic lesions of the PMd did not reduce TMT-induced freezing, but diminished post-shock and shock-induced contextually conditioned freezing, suggesting a role for the PMd in contextually conditioned fear. In contrast, electrolytic lesions of the AHN and VMH reduced freezing to TMT while not affecting conditioned fear. However, neither NMDA lesions of the AHN nor ibotenic acid lesions of the VMH reduced freezing in shock-induced conditioned or TMT-induced unconditioned fear paradigms. The data suggest that fibers passing through the AHN and VMH, and not cells in the MHDC, mediate unconditioned freezing to the predator odor TMT.

Investigation of the hypothalamic defensive system in the mouse

The hypothalamus plays especially important roles in various endocrine, autonomic, and behavioral responses that guarantee the survival of both the individual and the species. In the rat, a distinct hypothalamic defensive circuit has been defined as critical for integrating predatory threats, raising an important question as to whether this concept could be applied to other prey species. To start addressing this matter, in the present study, we investigated, in another prey species (the mouse), the pattern of hypothalamic Fos immunoreactivity in response to exposure to a predator (a rat, using the Rat Exposure Test). During rat exposure, mice remained concealed in the home chamber for a longer period of time and increased freezing and risk assessment activity. We were able to show that the mouse and the rat present a similar pattern of hypothalamic activation in response to a predator. Of particular note, similar to what has been described for the rat, we observed in the mouse that predator exposure induces a striking activation in the elements of the medial hypothalamic defensive system, namely, the anterior hypothalamic nucleus, the dorsomedial part of the ventromedial hypothalamic nucleus and the dorsal premammillary nucleus. Moreover, as described for the rat, predator-exposed mice also presented increased Fos levels in the autonomic and parvicellular parts of the paraventricular hypothalamic nucleus, lateral preoptic area and subfornical region of the lateral hypothalamic area. In conclusion, the present data give further support to the concept that a specific hypothalamic defensive circuit should be preserved across different prey species.