Medial Nucleus Of The Amygdala Research Articles

Dietary omega-3 polyunsaturated fatty acids reduce cytochrome c oxidase in brain white matter and sensorimotor regions while increasing functional interactions between neural systems related to escape behavior in postpartum rats.

Previously, we showed that omega-3 polyunsaturated fatty acid n-3 (PUFA) supplementation improved the performance of postpartum rats in the shuttle box escape test (SBET). The brains of these rats were used in the current study which examined brain cytochrome c oxidase (CCO) activity in white matter bundles and 39 regions spanning sensorimotor, limbic, and cognitive areas to determine the effects of n-3 PUFAs on neural metabolic capacity and network interactions. We found that n-3 PUFA supplementation decreased CCO activity in white matter bundles, deep and superficial areas within the inferior colliculus, the anterior and barrel field regions of the primary somatic sensorimotor cortex, the secondary somatic sensorimotor cortex, the lateral, anterior regions of the secondary visual cortex and the ventral posterior nucleus of the thalamus, and the medial nucleus of the amygdala. Structural equation modeling revealed that animals consuming diets without n-3 PUFAs exhibited fewer inter-regional interactions when compared to those fed diets with n-3 PUFAs. Without n-3 PUFAs, inter-regional interactions were observed between the posterior cingulate cortex and amygdala as well as among amygdala subregions. With n-3 PUFAs, more inter-regional interactions were observed, particularly between regions associated with fear memory processing and escape. Correlations between regional CCO activity and SBET behavior were observed in rats lacking dietary n-3 PUFAs but not in those supplemented with these nutrients. In conclusion, consumption of n-3 PUFAs results in reduced CCO activity in white matter bundles and sensorimotor regions, reflecting more efficient neurotransmission, and an increase in inter-regional interactions, facilitating escape from footshock.

The amygdaloid body of the family Delphinidae: a morphological study of its central nucleus through calbindin-D28k.

The amygdala is a noticeable bilateral structure in the medial temporal lobe and it is composed of at least 13 different nuclei and cortical areas, subdivided into the deep nuclei, the superficial nuclei, and the remaining nuclei which contain the central nucleus (CeA). CeA mediates the behavioral and physiological responses associated with fear and anxiety through pituitary-adrenal responses by modulating the liberation of the hypothalamic Corticotropin Releasing Factor/Hormone. Five dolphins of three different species, belonging to the family Delphinidae (three striped dolphins, one common dolphin, and one Atlantic spotted dolphin), were used for this study. For a precise overview of the CeA's structure, thionine staining and the immunoperoxidase method using calbindin D-28k were employed. CeA extended mainly dorsal to the lateral nucleus and ventral to the striatum. It was medial to the internal capsule and lateral to the optic tract and the medial nucleus of the amygdala. The dolphin amygdaloid complex resembles that of primates, including the subdivision, volume, and location of the CeA.

Automated subfield volumetric analysis of amygdala, hippocampus, and thalamic nuclei in mesial temporal lobe epilepsy

PurposeIdentifying relationships between clinical features and quantitative characteristics of the amygdala-hippocampal and thalamic subregions in mesial temporal lobe epilepsy (mTLE) may offer insights into pathophysiology and the basis for imaging prognostic markers of treatment outcome. Our aim was to ascertain different patterns of atrophy or hypertrophy in mesial temporal sclerosis (MTS) patients and their associations with post-surgical seizure outcomes. To assess this aim, this study is designed in 2 folds: (1) hemispheric changes within MTS group and (2) association with postsurgical seizure outcomes. Methods and materials27 mTLE subjects with mesial temporal sclerosis (MTS) were scanned for conventional 3D T1w MPRAGE images and T2w scans. With respect to 12 months post-surgical seizure outcomes, 15 subjects reported being seizure free (SF) and 12 reported continued seizures. Quantitative automated segmentation and cortical parcellation were performed using Freesurfer. Automatic labeling and volume estimation of hippocampal subfields, amygdala, and thalamic subnuclei were also performed. The volume ratio (VR) for each label was computed and compared between (1) between contralateral and ipsilateral MTS using Wilcoxon rank-sum test and (2) SF and not seizure free (NSF) groups using linear regression analysis. False Discovery rate (FDR) with significant level of 0.05 were used in both analyses to correct for multiple comparisons. ResultsAmygdala: The medial nucleus of the amygdala was the most significantly reduced in patients with continued seizures when compared to patients who remained seizure free. Hippocampus: Comparison of ipsilateral and contralateral volumes with seizure outcomes showed volume loss was most evident in the mesial hippocampal regions such as CA4 and hippocampal fissure. Volume loss was also most explicit in the presubiculum body in patients with continued seizures at the time of their follow-up. Ipsilateral MTS compared to contralateral MTS analysis showed the heads of the ipsilateral subiculum, presubiculum, parasubiculum, dentate gyrus, CA4, and CA3 were more significantly affected than their respective bodies. Volume loss was most noted in mesial hippocampal regions. Thalamus: VPL and PuL were the most significantly reduced thalamic nuclei in NSF patients. In all statistically significant areas, volume reduction was observed in the NSF group. No significant volume reductions were noted in the thalamus and amygdala when comparing ipsilateral to contralateral sides in mTLE subjects. ConclusionsVarying degrees of volume loss were demonstrated in the hippocampus, thalamus, and amygdala subregions of MTS, especially between patients who remained seizure-free and those who did not. The results obtained can be used to further understand mTLE pathophysiology. Clinical relevance/applicationIn the future, we hope these results can be used to deepen the understanding of mTLE pathophysiology, leading to improved patient outcomes and treatments.

Effects of Probiotic Bacteria on Central Neuronal Activation in Experimental Colitis.

Brain-gut axis dysregulation is observed in inflammatory bowel disease. However, the effect of altered gut flora on neuro- immunomodulation and its role in the pathogenesis of inflammatory bowel disease are unknown. The aims of this study are to determine (i) whether colitis modifies the expression of c-fos, a marker of general neuronal activation in the brain and (ii) whether this activation could be modulated by probiotic bacteria. In this study, 28 Sprague-Dawley rats were divided into 4 groups: colitis-probiotic group, non-colitis-fed-control group receiv- ing probiotic Lactobacillus delbrueckii subsp. Bulgaricus B3 strain for 7 days, colitis group, and sham group receiving only sodium chlo- ride. Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid-ethanol. The expression of c-fos was detected by immunohistochemistry in the brain tissue. Cytokines and inflammatory mediators were analyzed in the plasma. Histological scores and oxidative status were analyzed in the colon samples. The inflammatory response was accompanied by increased levels of cytokines, lipid peroxidation activities, c-fos expression in the medial nucleus of the amygdala, and decreased levels of antioxidant enzymes in the colitis (P < .001). Probiotic treatment reversed those effects. Also, histopathologic scores were significantly lower in the probiotic-treated groups compared to the colitis group (P = .035). In contrast, the expression of c-fos was significantly increased in the paraventricular nucleus of hypothalamus in the probiotic- treated rats (P < .001). Colitis and intestinal inflammation are associated with the activation of neurons in the limbic system creating stress-like effects in the brain. Probiotics diversely modulate limbic response and hypothalamic axis activity in addition to protective effects in inflammation.

Stimulation of medial amygdala GABA neurons with kinetically different channelrhodopsins yields opposite behavioral outcomes.

The medial amygdala (MeA) receives pheromone information about conspecifics and has crucial functions in social behaviors. A previous study showed that activation of GABA neurons in the postero-dorsal MeA (MeApd) with channelrhodopsin-2H134R (ChR2) stimulates inter-male aggression. When performing these experiments using the faster channelrhodopsinH134R,E123T (ChETA), we find the opposite behavioral outcome. A systematic comparison between the two channelrhodopsin variants reveals that optogenetic activation of MeApd GABA neurons with ChETA suppresses aggression, whereas activation under ChR2 increases aggression. Although the mechanism for this paradoxical difference is not understood, we observe that activation of MeApd GABA neurons with ChR2 causes larger plateau depolarizations, smaller action potentials, and larger local inhibition than with ChETA. Thus, the channelrhodopsin variant used for invivo optogenetic experiments can radically influence the behavioral outcome. Future work should continue to study the role of specific sub-populations of MeApd GABA neurons in aggression control.

Distinct Dynamics of Theta and Gamma Rhythmicity during Social Interaction Suggest Differential Mode of Action in the Medial Amygdala of Sprague Dawley Rats and C57BL/6J Mice

The medial nucleus of the amygdala (MeA) is known to regulate social behavior. This brain area is functionally positioned in a crossroads between sensory information processing and behavioral modulation. On the one hand, it receives direct chemosensory input from the accessory olfactory bulb. On the other hand, it orchestrates various behavioral outputs via brain-wide projections under the regulation of multiple neuromodulatory systems. Previously, we showed that adult male Sprague Dawley (SD) rats and C57BL/6J mice, the most widely used rodent models in neuroscience research, differ in their dynamics of motivation to interact with a novel same-sex conspecific and that this difference correlates with the level of c-Fos expression in the MeA. Here we used chronically implanted electrodes to compare rhythmic local field potential signals recorded from these animals during free and restricted social interactions. We found a significant induction of rhythmicity in the theta (4–12 Hz) and gamma (30–80 Hz) bands during both free and restricted social interaction in both rats and mice. However, the induction of gamma rhythmicity, thought to reflect activity of local neuronal networks, was significantly higher in rats than mice. Nevertheless, in contrast to rats, mice exhibited induction of rhythmicity, in both the theta and gamma bands, in synchrony with investigation of social, but not object stimuli. These results suggest that during interaction with a novel same-sex conspecific, the MeA of C57BL/6J mice is mostly involved in sensory information processing while in SD rats it is mainly active in modulating the social motivation state of the animal.

Neuregulin-1-dependent control of amygdala microcircuits is critical for fear extinction

The posttraumatic stress disorder is marked by an impaired ability to extinct fear memory acquired in trauma. Although previous studies suggest that fear extinction depends on the function of the amygdala, the underlying mechanisms are unclear. We found that NRG1 receptors (ErbB4) were abundantly expressed in the intercalated cells mass of amygdala (ITC). The NRG1-ErbB4 pathway in the ITC promotes fear extinction. The NRG1-ErbB4 pathway in the ITC did not affect excitatory input to ITC neurons from BLA neurons but increased feed-forward inhibition of (the central medial nucleus of the amygdala) CeM neurons through increased GABAergic neurotransmission of ITC neurons. We also found that the NRG1-ErbB4 signaling pathway in ITC might regulate fear extinction through P/Q-type voltage-activated Ca2+ channels (VACCs) but not through L- or N-type VACCs. Overall, our results suggest that the NRG1-ErbB4 signaling pathway in the ITC might represent a potential target for the treatment of anxiety disorders.

Effects of ovariectomy on the inputs from the medial nucleus of the amygdala to the ventromedial nucleus of the hypothalamus in young adult rats

During puberty, sexual hormones induce crucial changes in neural circuit organization, leading to significant sexual dimorphism in adult behaviours. The ventrolateral division of the ventromedial nucleus of the hypothalamus (VMHvl) is the major neural site controlling the receptive component of female sexual behaviour, which is dependent on ovarian hormones. The inputs to the VMHvl, originating from the medial nucleus of the amygdala (MeA), transmit essential information to trigger such behaviour. In this study, we investigated the projection pattern of the MeA to the VMHvl in ovariectomized rats at early puberty. Six-week-old Sprague-Dawley rats were ovariectomized (OVX) and, upon reaching 90 days of age, were subjected to iontophoretic injections of the neuronal anterograde tracer Phaseolus vulgaris leucoagglutinin into the MeA. Projections from the MeA to the VMHvl and to other structures included in the neural circuit responsible for female sexual behaviour were analysed in the Control and OVX groups. The results of the semi-quantitative analysis showed that peripubertal ovariectomy reduced the density of intra-amygdalar fibres. The stereological estimates, however, failed to find changes in the organization of the terminal fields of nerve fibres from the MeA to the VMHvl in the adult. The present data show that ovariectomized rats during the peripubertal phase did not undergo significant changes in MeA fibres reaching the VMHvl; however, they suggest a possible effect of ovariectomy on MeA connectivity under amygdalar subnuclei.

Structural-Functional Organization and Genoarchitectonics of the Medial Amygdaloid Nucleus of the Telencephalon

This review provides the first summary of the literature from the last decade characterizing the cytoarchitectonics, neuronal organization, and electron microscopic characteristics of neurons in the medial nucleus (MN) of the amygdala (A) of the telencephalon and the representation within it of neurotransmitter systems. Data are presented evidencing the involvement of the MN in functional processes linked with instinctive behavior – feeding, aggressive-defensive, and reproductive – whose realization is mediated by the hypothalamus. Data on the genoarchitectonics of this nucleus show that the MN is formed as a derivative of subpallial (anterior geniculate area), pallial (ventral pallium), and extratelencephalic (preoptic area) progenitor domains. The multiplicity and diversity of histogenetic domains involved in forming the MN provide evidence of complex multistage occurring in the A during evolutionary processes.

The effects of Topiramate on isolation-induced aggression: a behavioral and immunohistochemical study in mice.

Topiramate, an antiepileptic drug, has been found to be useful for the treatment of aggression in clinical populations. Most preclinical studies related to Topiramate have been focused exclusively on the quantitative aspects of the aggressive behavior between mice. However, there is still limited knowledge regarding the effects of Topiramate on neuronal mechanisms occurring in aggressive mice. The present work aims to understand further the effects of the antiepileptic drug Topiramate on aggressive behaviors, and on the neural correlates underlying such behaviors. To achieve this, we combined the resident-intruder model of isolation-induced aggression in mice with two drug regimens of Topiramate administration (30.0 mg/kg; acute and sub-chronic treatments). Our data showed that both acute and subchronic treatments decreased the intensity of agonistic encounters and reinforced social behavior. By using C-fos immunoreactivity, we investigated the neuronal activation of several brain regions involved in aggressive behavior following subchronic treatment. We found that Topiramate produced activation in several cortical areas and in the lateral septum of resident brain mice compared with their controls. However, Topiramate induced inhibition in the medial nucleus of the amygdala, the dorsomedial nucleus of the periaqueductal gray, and especially in the anterior hypothalamic nucleus. Finally, we performed microinfusion of Topiramate (0.1 and 0.3 mM) into the lateral septum and anterior hypothalamus on offensive behaviors in isolation-induced-aggression paradigm. Interestingly, the microinfusion of Topiramate into the lateral septum has the capacity to alleviate aggressive behavior, without affecting social behavior. However, the microinfusion of Topiramate into the anterior hypothalamus decreased aggressive behavior and slightly reinforced social behavior. Our observations supported that the dose of 0.1 mM of Topiramate appeared more efficacy to treat aggression in adult mice. These pharmacological characteristics may account for Topiramate efficacy on aggressive symptoms in psychiatric patients.

Neonatal shaking brain injury changes psychological stress-induced neuronal activity in adult male rats

Neonatal shaking brain injury (SBI) leads to increases in anxiety-like behavior and altered hormonal responses to psychological stressors as adults. These abnormalities are hypothesized to be due to a change in sensitization in neuronal circuits as a consequence of neonatal SBI. We examined the effects of neonatal SBI on neuronal activity in the anxiety- and/or stress-related areas of adult rats using Fos immunohistochemistry. Exposure to a novel elevated plus maze (EPM) resulted in a marked increase in Fos expression in the parvocellular (PVNp) and magnocellular parts of the paraventricular nucleus and the ventral part of the bed nucleus of the stria terminalis (vBNST) of shaken rats (S group) compared to non-shaken control rats (C group). On the contrary, Fos expression was significantly lower in the medial nucleus of the amygdala and the ventral subiculum (vS) of S group rats than C group rats exposed to EPM. Although we found no significant correlation in the number of Fos-expressing cells in the vBNST and PVNp in the C group rats, these numbers were significantly correlated in the S group rats. Furthermore, in the S group rats, but not in the C group rats, the number of Fos-expressing cells in the vBNST was inversely correlated with that in the vS. Interestingly, previous neuronal tracing studies have demonstrated direct projections from the vS to the vBNST and from the vBNST to the PVNp. The present data suggest that neonatal SBI can alter neuronal activity in anxiety- and/or stress-related neuronal circuits.

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice.

It has been 45 years since Gunther Schlager used a cross breeding program in mice to develop inbred strains with high, normal, and low blood pressure (BPH/2, BPN/3, and BPL/1 respectively). Thus, it is timely to gather together the studies that have characterized and explored the mechanisms associated with the hypertension to take stock of exactly what is known and what remains to be determined. Growing evidence supports the notion that the mechanism of hypertension in BPH/2 mice is predominantly neurogenic with some of the early studies showing aberrant brain noradrenaline levels in BPH/2 compared with BPN/3. Analysis of the adrenal gland using microarray suggested an association with the activity of the sympathetic nervous system. Indeed, in support of this, there is a larger depressor response to ganglion blockade, which reduced blood pressure in BPH/2 mice to the same level as BPN/3 mice. Greater renal tyrosine hydroxylase staining and greater renal noradrenaline levels in BPH/2 mice suggest sympathetic hyperinnervation of the kidney. Renal denervation markedly reduced the blood pressure in BPH/2 but not BPN/3 mice, confirming the importance of renal sympathetic nervous activity contributing to the hypertension. Further, there is an important contribution to the hypertension from miR-181a and renal renin in this strain. BPH/2 mice also display greater neuronal activity of amygdalo-hypothalamic cardiovascular regulatory regions. Lesions of the medial nucleus of the amygdala reduced the hypertension in BPH/2 mice and abolished the strain difference in the effect of ganglion blockade, suggesting a sympathetic mechanism. Further studies suggest that aberrant GABAergic inhibition may play a role since BPH/2 mice have low GABAA receptor δ, α4 and β2 subunit mRNA expression in the hypothalamus, which are predominantly involved in promoting tonic neuronal inhibition. Allopregnanolone, an allosteric modulator of GABAA receptors, which increase the expression of these subunits in the amygdala and hypothalamus, is shown to reduce the hypertension and sympathetic nervous system contribution in BPH/2 mice. Thus far, evidence suggests that BPH/2 mice have aberrant GABAergic inhibition, which drives neuronal overactivity within amygdalo-hypothalamic brain regions. This overactivity is responsible for the greater sympathetic contribution to the hypertension in BPH/2 mice, thus making this an ideal model of neurogenic hypertension.

Induction of Fos expression in the rat brain after intragastric administration of dried bonito dashi

ABSTRACT Objectives: Dried bonito dashi, a traditional Japanese fish broth made from dried bonito tuna, enhances food palatability due to its specific umami flavor characteristics. However, the pattern of brain activation following dashi ingestion has not been previously investigated. Methods: We mapped activation sites of the rat brain after intragastric loads of dried bonito dashi by measuring neuronal levels of the Fos protein, a functional marker of neuronal activation. Results: Compared to intragastric saline, intragastric dashi administration produced enhanced Fos expression in four forebrain regions: the medial preoptic area, subfornical organ, habenular nucleus, and central nucleus of the amygdala. Interestingly, the medial preoptic area was found to be the only feeding-related hypothalamic area responsive to dashi administration. Moreover, dashi had no effect in the nucleus accumbens and ventral tegmental area, two connected sites known to be activated by highly palatable sugars and fats. In the hindbrain, dashi administration produced enhanced Fos expression in both visceral sensory (caudal nucleus of the solitary tract, dorsal part of the lateral parabrachial nucleus, and area postrema) and autonomic (rostral ventrolateral medulla, and caudal ventrolateral medulla) sites. Discussion: The results demonstrate the activation of discrete forebrain and hindbrain regions following intragastric loads of dried bonito dashi. Our data suggest that the gut–brain axis is the principal mediator of the postingestive effects associated with the ingestion of dashi.

Sex, Drugs, and the Medial Amygdala: A Model of Enhanced Sexual Motivation in the Female Rat.

Methamphetamine (METH) is a psychomotor stimulant that is reported to enhance sexual desire and behavior in both men and women, leading to increases in unplanned pregnancies, sexually-transmitted infections, and even comorbid psychiatric conditions. Here, we discuss our rodent model of increased sexually-motivated behaviors in which the co-administration of METH and the ovarian hormones, estradiol and progesterone, intensify the incentive properties of a sexual stimulus and increases measures of sexually-motivated behavior in the presence of an androgen-specific cue. We then present the neurobiological mechanisms by which this heightened motivational salience is mediated by the actions of METH and ovarian hormones, particularly progestins, in the posterodorsal medial nucleus of the amygdala (MePD), a key integration site for sexually-relevant sensory information with generalized arousal. We finally demonstrate the cellular and molecular mechanisms underlying this facilitation of sexual motivation by METH, including the upregulation, increased phosphorylation, and activation of progestin receptors (PRs) in the MePD by METH in the presence of ovarian hormones. Taken together, this work extends our understanding of the neurobiology of female sexual motivation.

Role of the posterodorsal medial amygdala in predator odour stress-induced puberty delay in female rats.

Puberty onset is influenced by various factors, including psychosocial stress. The present study investigated cat‐odour stress on puberty onset and oestrous cyclicity in rats. Female weanling rats were exposed to either soiled cat litter or fresh unused litter for 10 consecutive days. Following vaginal opening (VO), rats were smeared for 14 days to determine oestrous cyclicity. Anxiety‐like behaviour was assessed using standard anxiety tests. Brains were collected to determine corticotrophin‐releasing factor (CRF), CRF receptor 1 (CRF‐R1) and CRF receptor 2 (CRF‐R2) mRNA in the paraventricular nucleus (PVN), as well as the central nucleus of the amygdala (CEA) and the medial nucleus of the amygdala (MEA). Cat odour delayed VO and first oestrus, disrupted oestrous cycles and caused anxiogenic responses. Cat odour elicited increased CRF mRNA expression in the PVN but not in the CeA. CRF‐R1 and CRF‐R2 mRNA levels in the PVN and CeA were unaffected by cat odour; however, CRF‐R1 mRNA levels were decreased in the MeA. The role of CRF signalling in the MeA, particularly its posterodorsal subnucleus (MePD), with respect to pubertal timing was directly examined by unilateral intra‐MePD administration of CRF (0.2 nmol day‐1 for 14 days) via an osmotic mini‐pump from postnatal day 24 and was shown to delay VO and first oestrus. These data suggest that CRF signalling in the MePD may be associated with predator odour‐induced puberty delay.

Modulation of tonic immobility by GABAA and GABAB receptors of the medial amygdala

Tonic immobility (TI) is a temporary state of profound motor inhibition associated with great danger as the attack of a predator. Previous studies carried out in our laboratory evidenced high Fos-IR in the posteroventral region of the medial nucleus of the amygdala (MEA) after induction of the TI response. Here, we investigated the effects of GABAA and GABAB of the MEA on TI duration. Intra-MEA injections of the GABAA agonist muscimol and GABAB agonist baclofen reduced TI response, while intra-MEA injections of the GABAA antagonist bicuculline and GABAB antagonist phaclofen increased the TI response. Moreover, the effects observed with muscimol and baclofen administrations into MEA were blocked by pretreatment with bicuculline and phaclofen (at ineffective doses per se). Finally, the activation of GABAA and GABAB receptors in the MEA did not alter the spontaneous motor activity in the open field test. These data support the role of the GABAergic system of the MEA in the modulation of innate fear.

Neurons expressing estrogen receptor α differentially innervate the periaqueductal gray matter of female rats

The periaqueductal gray matter (PAG) is a brainstem site involved in distinct autonomic and behavioral responses. Among them, the motor control of female sexual behavior, including lordosis, is well described. Lordosis reflex is highly dependent on increasing levels of estradiol that occur in the afternoon of the proestrus day in normally cycling females. This effect is thought to be mediated primarily via actions in the ventromedial nucleus of the hypothalamus (VMH). By binding to estrogen receptor α (ERα), estradiol changes the activity of VMH neurons that project to the PAG. Evidence also exists for the coordination of PAG outputs by estradiol-responsive neurons outside the VMH. However, a comprehensive analysis of these circuitries is not available. Using stereotaxic injection of the retrograde tracer Fluorogold in distinct columns of the PAG we performed a systematic mapping of neurons innervating the PAG and those coexpressing ERα immunoreactivity. We found that the forebrain projections to PAG columns are largely segregated and that most of the ERα expressing neurons preferentially target the lateral and the ventrolateral columns. Dual labeled neurons were mostly found in the intermediate subdivision of the lateral septal nucleus, the posterior aspect of the medial bed nucleus of the stria terminalis, the medial preoptic nucleus, the striohypothalamic nucleus and the ventrolateral VMH. Few dual labeled neurons were also observed in the arcuate nucleus, in the posterodorsal subdivision of the medial nucleus of the amygdala and in the ventral premammillary nucleus. Our findings indicate that ERα modulates sexual behavior in female rats via an integrated neural network that differentially innervate the columns of the PAG.

Involvement of oxytocin and GABA in consolation behavior elicited by socially defeated individuals in mandarin voles

Consolation, which entails comforting contact directed toward a distressed party, is a common empathetic response in humans and other species with advanced cognition. Here, using the social defeat paradigm, we provide empirical evidence that highly social and monogamous mandarin voles (Microtus mandarinus) increased grooming toward a socially defeated partner but not toward a partner who underwent only separation. This selective behavioral response existed in both males and females. Accompanied with these behavioral changes, c-Fos expression was elevated in many of the brain regions relevant for emotional processing, such as the anterior cingulate cortex (ACC), bed nucleus of the stria terminalis, paraventricular nucleus (PVN), basal/basolateral and central nucleus of the amygdala, and lateral habenular nucleus in both sexes; in the medial preoptic area, the increase in c-Fos expression was found only in females, whereas in the medial nucleus of the amygdala, this increase was found only in males. In particular, the GAD67/c-Fos and oxytocin (OT)/c-Fos colocalization rates were elevated in the ACC and PVN, indicating selective activation of GABA and OT neurons in these regions. The “stressed” pairs matched their anxiety-like behaviors in the open-field test, and their plasma corticosterone levels correlated well with each other, suggesting an empathy-based mechanism. This partner-directed grooming was blocked by pretreatment with an OT receptor antagonist or a GABAA receptor antagonist in the ACC but not by a V1a subtype vasopressin receptor antagonist. We conclude that consolation behavior can be elicited by the social defeat paradigm in mandarin voles, and this behavior may be involved in a coordinated network of emotion-related brain structures, which differs slightly between the sexes. We also found that the endogenous OT and the GABA systems within the ACC are essential for consolation behavior in mandarin voles.

Essential Role of Histone Methyltransferase G9a in Rapid Tolerance to the Anxiolytic Effects of Ethanol.

Tolerance to ethanol-induced anxiolysis promotes alcohol intake, thus contributing to alcohol use disorder development. Recent studies implicate histone deacetylase-mediated histone H3K9 deacetylation in regulating neuropeptide Y expression during rapid ethanol tolerance to the anxiolytic effects of ethanol. Furthermore, the histone methyltransferase, G9a, and G9a-mediated H3K9 dimethylation (H3K9me2) have recently emerged as regulators of addiction and anxiety; however, their role in rapid ethanol tolerance is unknown. Therefore, we investigated the role of G9a-mediated H3K9me2 in neuropeptide Y expression during rapid ethanol tolerance. Adult male rats were administered one injection of n-saline followed by single acute ethanol injection (1 g/kg) 24 hours later (ethanol group) or 2 injections (24 hours apart) of either n-saline (saline group) or ethanol (tolerance group). Anxiety-like behaviors and global and Npy-specific G9a and H3K9me2 levels in the amygdala were measured. Effects of G9a inhibitor (UNC0642) treatment on behavioral and epigenetic measures were also examined. Acute ethanol produced anxiolysis and decreased global H3K9me2 and G9a protein levels in the central and medial nucleus of the amygdala as well as decreased occupancy levels of H3K9me2 and G9a near a putative binding site for cAMP-response element binding protein on the Npy gene. Two identical doses of ethanol produced no behavioral or epigenetic changes relative to controls, indicating development of rapid ethanol tolerance. Interestingly, treatment with UNC0642, before the second ethanol dose reversed rapid ethanol tolerance, decreased global H3K9me2 and increased neuropeptide Y levels in the central and medial nucleus of the amygdala. These results implicate amygdaloid G9a-mediated H3K9me2 mechanisms in regulating rapid tolerance to the anxiolytic effects of ethanol via neuropeptide Y expression regulation.

The caudo-ventral pallium is a novel pallial domain expressing Gdf10 and generating Ebf3-positive neurons of the medial amygdala.

In rodents, the medial nucleus of the amygdala receives direct inputs from the accessory olfactory bulbs and is mainly implicated in pheromone-mediated reproductive and defensive behaviors. The principal neurons of the medial amygdala are GABAergic neurons generated principally in the caudo-ventral medialganglionic eminence and preoptic area. Beside GABAergic neurons, the medial amygdala also contains glutamatergic Otp-expressing neurons cells generated in the lateral hypothalamic neuroepithelium and a non-well characterized Pax6-positive population. In the present work, we describe a novel glutamatergic Ebf3-expressing neuronal subpopulation distributed within the periphery of the postero-ventral medial amygdala. These neurons are generated in a pallial domain characterized by high expression of Gdf10. This territory is topologically the most caudal tier of the ventral pallium and accordingly, we named it Caudo-Ventral Pallium (CVP). In the absence of Pax6, the CVP is disrupted and Ebf3-expressing neurons fail to be generated. Overall, this work proposes a novelmodel of the neuronalcomposition of the medial amygdala and unravels for the first time a new novel pallial subpopulation originating from the CVP and expressing the transcription factor Ebf3.