Premenstrual dysphoric disorder (PMDD) is considered a severe form of premenstrual syndrome (PMS). As a key brain region involved in emotional regulation and stress responses, the amygdala has been implicated in the pathogenesis of PMS/PMDD. The amygdala is composed of multiple subregions, each playing distinct roles in emotion, memory, and stress responses, and forms complex brain areas. Summarizing the interconnections among amygdala, subregions and their connectivity with external areas, and exploringt the neuroimaging characteristics of the amygdala, as well as changes in its neural circuits and brain networks in these patients, will help provide a theoretical foundation for targeted modulation of amygdala function in the treatment of PMS/PMDD.
Humans ; Amygdala/diagnostic imaging* ; Female ; Premenstrual Dysphoric Disorder/pathology* ; Premenstrual Syndrome/pathology* ; Emotions/physiology* ; Magnetic Resonance Imaging

In modern society, people are increasingly exposed to chronic stress, leading to various mental disorders. However, the activities of brain regions, especially neural firing patterns related to specific behaviors, remain unclear. In this study, we introduce a novel approach, NeuroSync, which integrates open-field behavioral testing with electrophysiological recordings from emotion-related brain regions, specifically the central amygdala and the paraventricular nucleus of the hypothalamus, to explore the mechanisms of negative emotions induced by chronic stress in mice. By applying machine vision techniques, we quantified behaviors in the open field, and signal processing algorithms elucidated the neural underpinnings of the observed behaviors. Synchronizing behavioral and electrophysiological data revealed significant correlations between neural firing patterns and stress-related behaviors, providing insights into real-time brain activity underlying behavioral responses. This research combines deep learning and machine learning to synchronize high-resolution video and electrophysiological data, offering new insights into neural-behavioral dynamics under chronic stress conditions.
Animals ; Mice ; Male ; Emotions/physiology* ; Stress, Psychological/physiopathology* ; Action Potentials/physiology* ; Mice, Inbred C57BL ; Behavior, Animal/physiology* ; Machine Learning ; Amygdala/physiopathology* ; Neurons/physiology* ; Paraventricular Hypothalamic Nucleus/physiopathology* ; Brain/physiology*

BACKGROUND: Amygdala plays an important role in the neurobiological basis of panic disorder (PD), and the amygdala contains different subregions, which may play different roles in PD. The aim of the present study was to examine whether there are common or distinct patterns of functional connectivity of the amygdala subregions in PD using resting-state functional magnetic resonance imaging and to explore the relationship between the abnormal spontaneous functional connectivity patterns of the regions of interest (ROIs) and the clinical symptoms of PD patients. METHODS: Fifty-three drug-naïve, non-comorbid PD patients and 70 healthy controls (HCs) were recruited. Seed-based resting-state functional connectivity (rsFC) analyses were conducted using the bilateral amygdalae and its subregions as the ROI seed. Two samples t test was performed for the seed-based Fisher's z -transformed correlation maps. The relationship between the abnormal spontaneous functional connectivity patterns of the ROIs and the clinical symptoms of PD patients was investigated by Pearson correlation analysis. RESULTS: PD patients showed increased rsFC of the bilateral amygdalae and almost all the amygdala subregions with the precuneus/posterior cingulate gyrus compared with the HC group (left amygdala [lAMY]: t  = 4.84, P  <0.001; right amygdala [rAMY]: t  = 4.55, P  <0.001; left centromedial amygdala [lCMA]: t  = 3.87, P  <0.001; right centromedial amygdala [rCMA]: t  = 3.82, P  = 0.002; left laterobasal amygdala [lBLA]: t  = 4.33, P  <0.001; right laterobasal amygdala [rBLA]: t  = 4.97, P  <0.001; left superficial amygdala [lSFA]: t  = 3.26, P  = 0.006). The rsFC of the lBLA with the left angular gyrus/inferior parietal lobule remarkably increased in the PD group ( t  = 3.70, P  = 0.003). And most of the altered rsFCs were located in the default mode network (DMN). A significant positive correlation was observed between the severity of anxiety and the rsFC between the lSFA and the left precuneus in PD patients ( r  = 0.285, P  = 0.039). CONCLUSIONS Our research suggested that the increased rsFC of amygdala subregions with DMN plays an important role in the pathogenesis of PD. Future studies may further explore whether the rsFC of amygdala subregions, especially with the regions in DMN, can be used as a biological marker of PD.
Humans ; Panic Disorder ; Magnetic Resonance Imaging/methods* ; Amygdala ; Gyrus Cinguli ; Comorbidity

Integrating multisensory inputs to generate accurate perception and guide behavior is among the most critical functions of the brain. Subcortical regions such as the amygdala are involved in sensory processing including vision and audition, yet their roles in multisensory integration remain unclear. In this study, we systematically investigated the function of neurons in the amygdala and adjacent regions in integrating audiovisual sensory inputs using a semi-chronic multi-electrode array and multiple combinations of audiovisual stimuli. From a sample of 332 neurons, we showed the diverse response patterns to audiovisual stimuli and the neural characteristics of bimodal over unimodal modulation, which could be classified into four types with differentiated regional origins. Using the hierarchical clustering method, neurons were further clustered into five groups and associated with different integrating functions and sub-regions. Finally, regions distinguishing congruent and incongruent bimodal sensory inputs were identified. Overall, visual processing dominates audiovisual integration in the amygdala and adjacent regions. Our findings shed new light on the neural mechanisms of multisensory integration in the primate brain.
Animals ; Macaca ; Acoustic Stimulation ; Auditory Perception/physiology* ; Visual Perception/physiology* ; Amygdala/physiology* ; Photic Stimulation

Basolateral Nuclear Complex ; Amygdala ; Neural Pathways

The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases, such as depression and anxiety. Meanwhile, the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor (CB₁R), which is strongly expressed in the amygdala of non-human primates (NHPs). However, it remains largely unknown how the CB₁Rs in the amygdala of NHPs regulate mental diseases. Here, we investigated the role of CB₁R by knocking down the cannabinoid receptor 1 (CNR1) gene encoding CB₁R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA. We found that CB₁R knockdown in the amygdala induced anxiety-like behaviors, including disrupted night sleep, agitated psychomotor activity in new environments, and reduced social desire. Moreover, marmosets with CB₁R-knockdown had up-regulated plasma cortisol levels. These results indicate that the knockdown of CB₁Rs in the amygdala induces anxiety-like behaviors in marmosets, and this may be the mechanism underlying the regulation of anxiety by CB₁Rs in the amygdala of NHPs.
Animals ; Callithrix ; Receptors, Cannabinoid ; Anxiety ; Amygdala ; Cannabinoids ; Phenotype

Post-traumatic stress disorder (PTSD) has been reported to be associated with a higher risk of cardiovascular disease. The amygdala may have an important role in regulating cardiovascular function. This study aims to explore the effect of amygdala glutamate receptors (GluRs) on cardiovascular activity in a rat model of PTSD. A compound stress method combining electrical stimulation and single prolonged stress was used to prepare the PTSD model, and the difference of weight gain before and after modeling and the elevated plus maze were used to assess the PTSD model. In addition, the distribution of retrogradely labeled neurons was observed using the FluoroGold (FG) retrograde tracking technique. Western blot was used to analyze the changes of amygdala GluRs content. To further investigate the effects, artificial cerebrospinal fluid (ACSF), non-selective GluR blocker kynurenic acid (KYN) and AMPA receptor blocker CNQX were microinjected into the central nucleus of the amygdala (CeA) in the PTSD rats, respectively. The changes in various indices following the injection were observed using in vivo multi-channel synchronous recording technology. The results indicated that, compared with the control group, the PTSD group exhibited significantly lower weight gain (P < 0.01) and significantly decreased ratio of open arm time (OT%) (P < 0.05). Retrograde labeling of neurons was observed in the CeA after microinjection of 0.5 µL FG in the rostral ventrolateral medulla (RVLM). The content of AMPA receptor in the PTSD group was lower than that in the control group (P < 0.05), while there was no significant differences in RVLM neuron firing frequency and heart rate (P > 0.05) following ACSF injection. However, increases in RVLM neuron firing frequency and heart rate were observed after the injection of KYN or CNQX into the CeA (P < 0.05) in the PTSD group. These findings suggest that AMPA receptors in the amygdala are engaged in the regulation of cardiovascular activity in PTSD rats, possibly by acting on inhibitory pathways.
Rats ; Animals ; Rats, Sprague-Dawley ; Stress Disorders, Post-Traumatic ; Receptors, AMPA ; 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology* ; Receptors, Glutamate/metabolism* ; Amygdala ; Weight Gain ; Medulla Oblongata/physiology* ; Blood Pressure

OBJECTIVE: To investigate the underlying molecular mechanisms by which silence information regulator (SIRT) 2 and glutaminase (GLS) in the amygdala regulate social behaviors in autistic rats. METHODS: Rat models of autism were established by maternal sodium valproic acid (VPA) exposure in wild-type rats and SIRT2-knockout ( SIRT2 ^-/-) rats. Glutamate (Glu) content, brain weight, and expression levels of SIRT2, GLS proteins and apoptosis-associated proteins in rat amygdala at different developmental stages were examined, and the social behaviors of VPA rats were assessed by a three-chamber test. Then, lentiviral overexpression or interference vectors of GLS were injected into the amygdala of VPA rats. Brain weight, Glu content and expression level of GLS protein were measured, and the social behaviors assessed. RESULTS: Brain weight, amygdala Glu content and the levels of SIRT2, GLS protein and pro-apoptotic protein caspase-3 in the amygdala were increased in VPA rats, while the level of anti-apoptotic protein Bcl-2 was decreased (all P<0.01). Compared with the wild-type rats, SIRT2 ^-/- rats displayed decreased expression of SIRT2 and GLS proteins in the amygdala, reduced Glu content, and improved social dysfunction (all P<0.01). Overexpression of GLS increased brain weight and Glu content, and aggravated social dysfunction in VPA rats (all P<0.01). Knockdown of GLS decreased brain weight and Glu content, and improved social dysfunction in VPA rats (all P<0.01). CONCLUSIONS The glutamate circulatory system in the amygdala of VPA induced autistic rats is abnormal. This is associated with the upregulation of SIRT2 expression and its induced increase of GLS production; knocking out SIRT2 gene or inhibiting the expression of GLS is helpful in maintaining the balanced glutamate cycle and in improving the social behavior disorder of rats.
Animals ; Rats ; Amygdala/metabolism* ; Autistic Disorder/metabolism* ; Behavior, Animal ; Disease Models, Animal ; Glutamates/metabolism* ; Glutaminase/metabolism* ; Sirtuin 2/metabolism* ; Social Behavior

Epilepsy is a common neurological disorder characterized by hyperexcitability in the brain. Its pathogenesis is classically associated with an imbalance of excitatory and inhibitory neurons. Calretinin (CR) is one of the three major types of calcium-binding proteins present in inhibitory GABAergic neurons. The functions of CR and its role in neural excitability are still unknown. Recent data suggest that CR neurons have diverse neurotransmitters, morphologies, distributions, and functions in different brain regions across various species. Notably, CR neurons in the hippocampus, amygdala, neocortex, and thalamus are extremely susceptible to excitotoxicity in the epileptic brain, but the causal relationship is unknown. In this review, we focus on the heterogeneous functions of CR neurons in different brain regions and their relationship with neural excitability and epilepsy. Importantly, we provide perspectives on future investigations of the role of CR neurons in epilepsy.
Amygdala/metabolism* ; Calbindin 2/metabolism* ; Epilepsy ; GABAergic Neurons ; Hippocampus/metabolism* ; Humans

Chronic stress leads to many psychiatric disorders, including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala (BLA). However, not all individuals develop psychiatric diseases, many showing considerable resilience against stress exposure. Whether BLA neuronal activity is involved in regulating an individual's vulnerability to stress remains elusive. In this study, using a mouse model of chronic social defeat stress (CSDS), we divided the mice into susceptible and resilient subgroups based on their social interaction behavior. Using in vivo fiber photometry and in vitro patch-clamp recording, we showed that CSDS persistently (after 20 days of recovery from stress) increased BLA neuronal activity in all the mice regardless of their susceptible or resilient nature, although impaired social interaction behavior was only observed in susceptible mice. Increased anxiety-like behavior, on the other hand, was evident in both groups. Notably, the CSDS-induced increase of BLA neuronal activity correlated well with the heightened anxiety-like but not the social avoidance behavior in mice. These findings provide new insight to our understanding of the role of neuronal activity in the amygdala in mediating stress-related psychiatric disorders.
Amygdala ; Animals ; Anxiety/etiology* ; Anxiety Disorders ; Avoidance Learning ; Mice ; Mice, Inbred C57BL ; Social Behavior ; Stress, Psychological/complications*