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Psychoneuroendocrinology Aug 2024In mammals, some physiological conditions are associated with the high brain oxytocin (OXT) system activity. These include lactation in females and mating in males and...
In mammals, some physiological conditions are associated with the high brain oxytocin (OXT) system activity. These include lactation in females and mating in males and females, both of which have been linked to reduced stress responsiveness and anxiolysis. Also, in a murine model of social fear conditioning (SFC), enhanced brain OXT signaling in lactating mice, specifically in the lateral septum (LS), was reported to underlie reduced social fear expression. Here, we studied the effects of mating in male mice on anxiety-related behaviour, social (and cued) fear expression and its extinction, and the activity of OXT neurons reflected by cFos expression and OXT release in the LS and amygdala. We further focused on the involvement of brain OXT in the mating-induced facilitation of social fear extinction. We could confirm the anxiolytic effect of mating in male mice irrespective of the occurrence of ejaculation. Further, we found that only successful mating resulting in ejaculation (Ej) facilitated social fear extinction, whereas mating without ejaculation (Ej) did not. In contrast, mating did not affect cues fear expression. Using the cellular activity markers cFos and pErk, we further identified the ventral LS (vLS) as a potential region participating in the effect of ejaculation on social fear extinction. In support, microdialysis experiments revealed a rise in OXT release within the LS, but not the amygdala, during mating. Finally, infusion of an OXT receptor antagonist into the LS before mating or into the lateral ventricle (icv) after mating demonstrated a significant role of brain OXT receptor-mediated signaling in the mating-induced facilitation of social fear extinction.
Topics: Animals; Fear; Oxytocin; Male; Extinction, Psychological; Mice; Female; Sexual Behavior, Animal; Amygdala; Social Behavior; Anxiety; Receptors, Oxytocin; Septal Nuclei; Ejaculation; Copulation; Septum of Brain; Mice, Inbred C57BL; Behavior, Animal
PubMed: 38788461
DOI: 10.1016/j.psyneuen.2024.107083 -
Theranostics 2024Methamphetamine (METH) withdrawal anxiety symptom and relapse have been significant challenges for clinical practice, however, the underlying neuronal basis remains...
Methamphetamine (METH) withdrawal anxiety symptom and relapse have been significant challenges for clinical practice, however, the underlying neuronal basis remains unclear. Our recent research has identified a specific subpopulation of choline acetyltransferase (ChAT) neurons localized in the external lateral portion of parabrachial nucleus (eLPB), which modulates METH primed-reinstatement of conditioned place preference (CPP). Here, the anatomical structures and functional roles of eLPB projections in METH withdrawal anxiety and primed reinstatement were further explored. In the present study, a multifaceted approach was employed to dissect the LPB projections in male mice, including anterograde and retrograde tracing, acetylcholine (Ach) indicator combined with fiber photometry recording, photogenetic and chemogenetic regulation, as well as electrophysiological recording. METH withdrawal anxiety-like behaviors and METH-primed reinstatement of conditioned place preference (CPP) were assessed in male mice. We identified that eLPB send projections to PKCδ-positive (PKCδ) neurons in lateral portion of central nucleus of amygdala (lCeA) and oval portion of bed nucleus of the stria terminalis (ovBNST), forming eLPB-lCeA and eLPB-ovBNST pathways. At least in part, the eLPB neurons positively innervate lCeA neurons and ovBNST neurons through regulating synaptic elements of presynaptic Ach release and postsynaptic nicotinic acetylcholine receptors (nAChRs). METH withdrawal anxiety and METH-primed reinstatement of CPP respectively recruit eLPB-lCeA pathway and eLPB-ovBNST pathway in male mice. Our findings put new insights into the complex neural networks, especially focusing on the eLPB projections. The eLPB is a critical node in the neural networks governing METH withdrawal anxiety and primed-reinstatement of CPP through its projections to the lCeA and ovBNST, respectively.
Topics: Animals; Methamphetamine; Male; Mice; Substance Withdrawal Syndrome; Anxiety; Mice, Inbred C57BL; Neurons; Choline O-Acetyltransferase; Septal Nuclei; Behavior, Animal
PubMed: 38773977
DOI: 10.7150/thno.95383 -
Progress in Neuro-psychopharmacology &... Jul 2024Early life stress may induce synaptic changes within brain regions associated with behavioral disorders. Here, we investigated glutamatergic functional connectivity by a...
Early life stress may induce synaptic changes within brain regions associated with behavioral disorders. Here, we investigated glutamatergic functional connectivity by a postsynaptic density immediate-early gene-based network analysis. Pregnant female Sprague-Dawley rats were randomly divided into two experimental groups: one exposed to stress sessions and the other serving as a stress-free control group. Homer1 expression was evaluated by in situ hybridization technique in eighty-eight brain regions of interest of male rat offspring. Differences between the perinatal stress exposed group (PRS) (n = 5) and the control group (CTR) (n = 5) were assessed by performing the Student's t-test via SPSS 28.0.1.0 with Bonferroni correction. Additionally, all possible pairwise Spearman's correlations were computed as well as correlation matrices and networks for each experimental group were generated via RStudio and Cytoscape. Perinatal stress exposure was associated with Homer1a reduction in several cortical, thalamic, and striatal regions. Furthermore, it was found to affect functional connectivity between: the lateral septal nucleus, the central medial thalamic nucleus, the anterior part of the paraventricular thalamic nucleus, and both retrosplenial granular b cortex and hippocampal regions; the orbitofrontal cortex, amygdaloid nuclei, and hippocampal regions; and lastly, among regions involved in limbic system. Finally, the PRS networks showed a significant reduction in multiple connections for the ventrolateral part of the anteroventral thalamic nucleus after perinatal stress exposure, as well as a decrease in the centrality of ventral anterior thalamic and amygdaloid nuclei suggestive of putative reduced cortical control over these regions. Within the present preclinical setting, perinatal stress exposure is a modifier of glutamatergic early gene-based functional connectivity in neuronal circuits involved in behaviors relevant to model neurodevelopmental disorders.
Topics: Animals; Female; Pregnancy; Homer Scaffolding Proteins; Stress, Psychological; Rats, Sprague-Dawley; Rats; Male; Prenatal Exposure Delayed Effects; Genes, Immediate-Early; Post-Synaptic Density; Glutamic Acid; Brain; Gene Regulatory Networks
PubMed: 38762163
DOI: 10.1016/j.pnpbp.2024.111032 -
Science Advances May 2024Corticotropin releasing factor (CRF) network in the oval nucleus of bed nuclei of the stria terminalis (ovBNST) is generally indicated in stress, but its role in...
Corticotropin releasing factor (CRF) network in the oval nucleus of bed nuclei of the stria terminalis (ovBNST) is generally indicated in stress, but its role in female-biased susceptibility to anxiety is unknown. Here, we established a female-biased stress paradigm. We found that the CRF release in ovBNST during stress showed female-biased pattern, and ovBNST CRF neurons were more prone to be hyperexcited in female mice during stress in both in vitro and in vivo studies. Moreover, optogenetic modulation to exchange the activation pattern of ovBNST CRF neurons during stress between female and male mice could reverse their susceptibility to anxiety. Last, CRF receptor type 1 (CRFR1) mediated the CRF-induced excitation of ovBNST CRF neurons and showed female-biased expression. Specific knockdown of the CRFR1 level in ovBNST CRF neurons in female or overexpression that in male could reverse their susceptibility to anxiety. Therefore, we identify that CRFR1-mediated hyperexcitation of ovBNST CRF neurons in female mice encode the female-biased susceptibility to anxiety.
Topics: Animals; Female; Male; Mice; Anxiety; Avoidance Learning; Behavior, Animal; Corticotropin-Releasing Hormone; Neurons; Receptors, Corticotropin-Releasing Hormone; Septal Nuclei; Stress, Psychological
PubMed: 38728397
DOI: 10.1126/sciadv.adk7636 -
Biological Psychiatry May 2024Social memory, the ability to recognize and remember individuals within a social group, is crucial for social interactions and relationships. Deficits in social memory... (Review)
Review
Social memory, the ability to recognize and remember individuals within a social group, is crucial for social interactions and relationships. Deficits in social memory have been linked to several neuropsychiatric and neurodegenerative disorders. The hippocampus, especially the circuit that links dorsal CA2 and ventral CA1 neurons, is considered a neural substrate for social memory formation. Recent studies have provided compelling evidence of extrahippocampal contributions to social memory. The septal nuclei, including the medial and lateral septum, make up a basal forebrain region that shares bidirectional neuronal connections with the hippocampus and has recently been identified as critical for social memory. The focus of our review is the neural circuit mechanisms that underlie social memory, with a special emphasis on the septum. We also discuss the social memory dysfunction associated with neuropsychiatric and neurodegenerative disorders.
PubMed: 38718881
DOI: 10.1016/j.biopsych.2024.04.018 -
Proceedings of the National Academy of... May 2024One of the largest sex differences in brain neurochemistry is the expression of the neuropeptide arginine vasopressin (AVP) within the vertebrate brain, with males...
One of the largest sex differences in brain neurochemistry is the expression of the neuropeptide arginine vasopressin (AVP) within the vertebrate brain, with males having more AVP cells in the bed nucleus of the stria terminalis (BNST) than females. Despite the long-standing implication of AVP in social and anxiety-like behaviors, the circuitry underlying AVP's control of these behaviors is still not well defined. Using optogenetic approaches, we show that inhibiting AVP BNST cells reduces social investigation in males, but not in females, whereas stimulating these cells increases social investigation in both sexes, but more so in males. These cells may facilitate male social investigation through their projections to the lateral septum (LS), an area with the highest density of sexually differentiated AVP innervation in the brain, as optogenetic stimulation of BNST AVP → LS increased social investigation and anxiety-like behavior in males but not in females; the same stimulation also caused a biphasic response of LS cells ex vivo. Blocking the vasopressin 1a receptor (V1aR) in the LS eliminated all these responses. Together, these findings establish a sexually differentiated role for BNST AVP cells in the control of social investigation and anxiety-like behavior, likely mediated by their projections to the LS.
Topics: Animals; Female; Male; Mice; Anxiety; Arginine Vasopressin; Behavior, Animal; Mice, Inbred C57BL; Neurons; Optogenetics; Receptors, Vasopressin; Septal Nuclei; Social Behavior
PubMed: 38709918
DOI: 10.1073/pnas.2319641121 -
Molecular Brain May 2024We previously reported that enhanced corticotropin-releasing factor (CRF) signaling in the bed nucleus of the stria terminalis (BNST) caused the aversive responses...
We previously reported that enhanced corticotropin-releasing factor (CRF) signaling in the bed nucleus of the stria terminalis (BNST) caused the aversive responses during acute pain and suppressed the brain reward system during chronic pain. However, it remains to be examined whether chronic pain alters the excitability of CRF neurons in the BNST. In this study we investigated the chronic pain-induced changes in excitability of CRF-expressing neurons in the oval part of the BNST (ovBNST neurons) by whole-cell patch-clamp electrophysiology. CRF-Cre; Ai14 mice were used to visualize CRF neurons by tdTomato. Electrophysiological recordings from brain slices prepared from a mouse model of neuropathic pain revealed that rheobase and firing threshold were significantly decreased in the chronic pain group compared with the sham-operated control group. Firing rate of the chronic pain group was higher than that of the control group. These data indicate that chronic pain elevated neuronal excitability of ovBNST neurons.
Topics: Animals; Septal Nuclei; Corticotropin-Releasing Hormone; Neurons; Chronic Pain; Male; Action Potentials; Mice, Inbred C57BL; Mice
PubMed: 38702738
DOI: 10.1186/s13041-024-01094-6 -
Nature Communications Apr 2024Understanding how distinct functional circuits are coordinated to fine-tune mood and behavior is of fundamental importance. Here, we observe that within the dense...
Understanding how distinct functional circuits are coordinated to fine-tune mood and behavior is of fundamental importance. Here, we observe that within the dense projections from basolateral amygdala (BLA) to bed nucleus of stria terminalis (BNST), there are two functionally opposing pathways orchestrated to enable contextually appropriate expression of anxiety-like behaviors in male mice. Specifically, the anterior BLA neurons predominantly innervate the anterodorsal BNST (adBNST), while their posterior counterparts send massive fibers to oval BNST (ovBNST) with moderate to adBNST. Optogenetic activation of the anterior and posterior BLA inputs oppositely regulated the activity of adBNST neurons and anxiety-like behaviors, via disengaging and engaging the inhibitory ovBNST-to-adBNST microcircuit, respectively. Importantly, the two pathways exhibited synchronized but opposite responses to both anxiolytic and anxiogenic stimuli, partially due to their mutual inhibition within BLA and the different inputs they receive. These findings reveal synergistic interactions between two BLA-to-BNST pathways for appropriate anxiety expression with ongoing environmental demands.
Topics: Animals; Male; Septal Nuclei; Anxiety; Basolateral Nuclear Complex; Mice; Optogenetics; Behavior, Animal; Neurons; Mice, Inbred C57BL; Neural Pathways
PubMed: 38658548
DOI: 10.1038/s41467-024-47966-2 -
Neuroscience and Biobehavioral Reviews Jun 2024The lateral septum (LS) is involved in controlling anxiety, aggression, feeding, and other motivated behaviors. Lesion studies have also implicated the LS in various... (Review)
Review
The lateral septum (LS) is involved in controlling anxiety, aggression, feeding, and other motivated behaviors. Lesion studies have also implicated the LS in various forms of caring behaviors. Recently, novel experimental tools have provided a more detailed insight into the function of the LS, including the specific role of distinct cell types and their neuronal connections in behavioral regulations, in which the LS participates. This article discusses the regulation of different types of maternal behavioral alterations using the distributions of established maternal hormones such as prolactin, estrogens, and the neuropeptide oxytocin. It also considers the distribution of neurons activated in mothers in response to pups and other maternal activities, as well as gene expressional alterations in the maternal LS. Finally, this paper proposes further research directions to keep up with the rapidly developing knowledge on maternal behavioral control in other maternal brain regions.
Topics: Maternal Behavior; Animals; Septal Nuclei; Female; Humans; Oxytocin
PubMed: 38649125
DOI: 10.1016/j.neubiorev.2024.105683 -
Scientific Reports Apr 2024The natural alignment of animals into social dominance hierarchies produces adaptive, and potentially maladaptive, changes in the brain that influence health and...
The natural alignment of animals into social dominance hierarchies produces adaptive, and potentially maladaptive, changes in the brain that influence health and behavior. Aggressive and submissive behaviors assumed by animals through dominance interactions engage stress-dependent neural and hormonal systems that have been shown to correspond with social rank. Here, we examined the association between social dominance hierarchy status established within cages of group-housed mice and the expression of the stress peptide PACAP in the bed nucleus of the stria terminalis (BNST) and central nucleus of the amygdala (CeA). We also examined the relationship between social dominance rank and blood corticosterone (CORT) levels, body weight, motor coordination (rotorod) and acoustic startle. Male C57BL/6 mice were ranked as either Dominant, Submissive, or Intermediate based on counts of aggressive/submissive encounters assessed at 12 weeks-old following a change in homecage conditions. PACAP expression was significantly higher in the BNST, but not the CeA, of Submissive mice compared to the other groups. CORT levels were lowest in Submissive mice and appeared to reflect a blunted response following events where dominance status is recapitulated. Together, these data reveal changes in specific neural/neuroendocrine systems that are predominant in animals of lowest social dominance rank, and implicate PACAP in brain adaptations that occur through the development of social dominance hierarchies.
Topics: Animals; Male; Mice; Amygdala; Corticosterone; Mice, Inbred C57BL; Pituitary Adenylate Cyclase-Activating Polypeptide; Septal Nuclei; Social Dominance; Stress, Psychological
PubMed: 38637645
DOI: 10.1038/s41598-024-59459-9