The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain functio...The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.展开更多
Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-...Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.展开更多
Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types...Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.展开更多
Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivi...Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivity of basolateral amygdala(BLA)pyramidal neurons(PNs)in Shank3 InsG3680 knock-in(InsG3680+/+)mice is involved in the development of anxiety.Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs.Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+mice.Further study found that the diminished control of the BLA by medial prefrontal cortex(mPFC)and optogenetic activation of the mPFC-BLA pathway also had a rescue effect,which increased the feedforward inhibition of the BLA.Taken together,our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+mice.展开更多
In polarized cells,the differential distribution of proteins results in the formation of apical and basolateral membranes.The basolateral membrane contacts basal lamina and mediates cell-to-cell communication,which is...In polarized cells,the differential distribution of proteins results in the formation of apical and basolateral membranes.The basolateral membrane contacts basal lamina and mediates cell-to-cell communication,which is crucial for maintaining homeostasis and enabling drug absorption.To establish and maintain the basolateral domain,intricate mechanisms are necessary to ensure the proper sorting and transportation of molecules.Sorting signals play a crucial role in regulating the distributions of basolateral proteins,determining their trafficking route and final residence.Newly synthesized proteins can be segregated into different carrier vesicles at either trans-Golgi network(TGN)or endosomes.Additionally,understanding basolateral transport in polarized epithelial cells is important for predicting diseases and delivering drugs.This review provides a summary of recent advancements in the mechanisms and applications of basolateral sorting and trafficking.展开更多
In this study we investigated whether GABAA receptors of the basolateral amygdala(BLA) interact with the effect of dexamethasone on the retrieval stage of memory.Adult male Wistar rats were bilaterally cannulated in t...In this study we investigated whether GABAA receptors of the basolateral amygdala(BLA) interact with the effect of dexamethasone on the retrieval stage of memory.Adult male Wistar rats were bilaterally cannulated in the BLA by stereotaxic surgery.The animals were trained in step-through apparatus by induction of electric shock(1.5 mA,3 s) and were tested for memory retrieval after 1 d.The time of latency for entering the dark compartment of the instrument and the time spent by rats in this chamber were recorded for evaluation of the animals' retrieval in passive avoidance memory.Administration of dexamethasone(0.3 and 0.9 mg/kg,subcutaneously(s.c.)),immediately after training,enhanced memory retrieval.This effect was reduced by intra-BLA microinjection of muscimol(0.125,0.250 and 0.500 μg/rat),when administered before 0.9 mg/kg of dexamethasone.Microinjection of bicuculline(0.75 μg/rat,intra-BLA) with an ineffective dose of dexamethasone(0.1 mg/kg,s.c.) increased memory retrieval.However,the same doses of muscimol and bicuculline without dexamethasone did not affect memory processes.Our data support reports that dexamethasone enhances memory retrieval.It seems that GABAA receptors of the BLA mediate the effect of dexamethasone on memory retrieval in rats.展开更多
This study was aimed to determine the effect of amygdaline inactivation on the sexual motivation of male rats during a T-maze task with a sexual reward. Subjects were chronically implanted with two stainless-steel can...This study was aimed to determine the effect of amygdaline inactivation on the sexual motivation of male rats during a T-maze task with a sexual reward. Subjects were chronically implanted with two stainless-steel cannulae that enabled the infusion of tetrodotoxin, a sodium channel blocker, into the left and right basolateral amygdala (BLA). Animals were divided into 3 groups: saline (SS);TTX1 (tetrodotoxin at 2.5 ng);and TTX2 (tetrodotoxin at 5.0 ng). To induce a sexually-motivated state, all male rats were allowed to have an intromission with a receptive female before performing the T-maze task, after which their sexual motivation was evaluated during seven trials in which a receptive female was placed in one goal-box of the T-maze, and a non-receptive one in the other. Subjects were allowed an intromission as a sexual reward whenever they reached the goal-box containing the receptive female, but were returned to the start-box if they did not. At the end of the experiment, copulation until ejaculation was permitted. Both doses of TTX increased the time rats required to cross the maze stem during the final trials. In terms of sexual interaction, the high dose of TTX increased more markedly mount, intromission and ejaculation latencies and the number of mounts and intromissions. Overall, these results indicate that the BLA may play an important role in modulating sexual behavior, particularly in maintaining sexual motivation in successive trials in a T-maze task and during sexual interaction per se.展开更多
Objective:To elucidate the modulation mechanism of Suanzaoren Decoction(SZRD)on basolateral amygdala(BLA)neuronal activity to alleviate chronic restraint stress(CRS)-related behavioral deficits.Methods:The male C57BL/...Objective:To elucidate the modulation mechanism of Suanzaoren Decoction(SZRD)on basolateral amygdala(BLA)neuronal activity to alleviate chronic restraint stress(CRS)-related behavioral deficits.Methods:The male C57BL/6J mice were assigned to 4 groups using the complete randomization method,including control(CON,n=19),CRS(n=19),SZRD(n=21),and fluoxetine(Flu,n=22)groups.Mice were restrained for 6 h per day,over a 21-d period to establish CRS models.The CON group remained in their cages without food or water during the 6-h matching period.SZRD and Flu groups received intragastric administration of SZRD(4.68 g/kg)and Flu(20 mg/kg)daily,respectively,30 min before restraint for 21 consecutive days.The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test,elevated plus maze test,and forced swimming test.The cellular Fletcher B.Judson murine osteosarcoma proto-oncogene(c-Fos)expression in the BLA was measured using immunofluorescence,while action potential(AP)firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings.Results:SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time(P<0.05or P<0.01).It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA(P<0.01).Additionally,SZRD selectively attenuated excitatory(P<0.01),but not inhibitory,synaptic transmission onto BLA pyramidal neurons.Conclusion:SZRD alleviated CRS-induced anxiety-and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.展开更多
Depression is a common and severely debilitating neuropsychiatric disorder.Multiple studies indicate a strong correlation between the occurrence of immunological inflammation and the presence of depression.The basolat...Depression is a common and severely debilitating neuropsychiatric disorder.Multiple studies indicate a strong correlation between the occurrence of immunological inflammation and the presence of depression.The basolateral amygdala(BLA)is crucial in the cognitive and physiological processing and control of emotion.However,due to the lack of detection tools,the neural activity of the BLA during depression is not well understood.In this study,a microelectrode array(MEA)based on the shape and anatomical location of the BLA in the brain was designed and manufactured.Rats were injected with lipopolysaccharide(LPS)for 7 consecutive days to induce depressive behavior.We used the MEA to detect neural activity in the BLA before modeling,during modeling,and after LPS administration on 7 consecutive days.The results showed that after LPS treatment,the spike firing of neurons in the BLA region of rats gradually became more intense,and the local field potential power also increased progressively.Further analysis revealed that after LPS administration,the spike firing of BLA neurons was predominantly in the theta rhythm,with obvious periodic firing characteristics appearing after the 7 d of LPS administration,and the relative power of the local field potential in the theta band also significantly increased.In summary,our results suggest that the enhanced activity of BLA neurons in the theta band is related to the depressive state of rats,providing valuable guidance for research into the neural mechanisms of depression.展开更多
Anxiety disorders are one of the most epidemic and chronic psychiatric disorders.An incom-plete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders.GP...Anxiety disorders are one of the most epidemic and chronic psychiatric disorders.An incom-plete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders.GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders.However,no study has investigated the role of GPR17 in psychiatric disorders.In a well-established chronic restraint stress(CRS)mouse model,using a combination of pharmacological and molecular biology techniques,viral tracing,in vitro electrophysiology recordings,in vivo fiber photom-etry,chemogenetic manipulations and behavioral tests,we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala(BLA)glutamatergic neurons.Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutama-tergic neurons effectively improved anxiety-like behaviors.Overexpression of GPR17 in BLA glutama-tergic neurons increased the susceptibility to anxiety-like behaviors.What's more,BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors via BLA to ventral hippocampal CAl glutamatergic projection.Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders.展开更多
The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts...The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts in the urine.Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced,as seen in familial renal glycosuria(FRG).FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene,which encodes the sodium-glucose cotransporter(SGLT)2.Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes,and since FRG is often considered an asymptomatic and benign condition,it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes.However,patients with FRG may exhibit clinical features such as lower body weight or height,altered systemic blood pressure,diaper dermatitis,amino-aciduria,decreased serum uric acid levels,and hypercalciuria.Further research is needed to fully understand the pathophysiology,molecular genetics,and clinical manifestations of renal glucosuria.展开更多
Background Glucocorticoid receptor （GR） is believed to be a major factor in brain maturation and in modulation of a series of brain activity. Hippocampal neurons are abundant in glucocorticoid receptor, and there is...Background Glucocorticoid receptor （GR） is believed to be a major factor in brain maturation and in modulation of a series of brain activity. Hippocampal neurons are abundant in glucocorticoid receptor, and there is significant change in GR expression under certain pathological state. Epilepsy is a special pathological state of the central nervous system. This study aimed to explore the role of GR in epilepsy by observing the change and functions of GR in hippocampus with a basolateral amygdale-electrical kindled rat epilepsy model. Methods Firstly, we established the basolateral amygdale-electrical kindled rat epilepsy model. Then GR mRNA expression in the hippocampus was assayed by semi-quantitative reverse transcription-PCR in this experiment. In addition, the processes of epileptic seizures were observed and electroencephalograms were recorded. One-way analysis of variance （ANOVA） was employed for comparing means of multiple groups, followed Fisher＇s least significant difference （LSD） for paired comparison. Results The rats were successfully kindled after an average of （13.50＋3.99） times electrical stimulation, in which it was showed that GR mRNA expression reduced obviously as compared with the control group and the sham groups （P 〈0.001）. The down-regulation of GR mRNA expression was abated or reversed by some anti-epilepsy drugs （P 〈0.001 compared with the epilepsy group）, accompanied by attenuation of seizures and improvement of electroencephalograms. Conclusions Down-regulation of hippocampal GR mRNA expression may be related to the kindling. Anti-epilepsy drugs exposure can retard this change.展开更多
BACKGROUND： The role of the amygdala in controlling emotional pain has been emphasized in several studies. In this study, the role of the NMDA glutamate receptors in the basolateral nucleus of the amygdala （BLA） in...BACKGROUND： The role of the amygdala in controlling emotional pain has been emphasized in several studies. In this study, the role of the NMDA glutamate receptors in the basolateral nucleus of the amygdala （BLA） in regulating inflammation and emotional pain, induced by formalin, was studied in male rats. METHODS： Male Wistar rats, weighing 250±0 g, were injected with 20 μL of 2% formalin into the paw of the right hind limb. Memantine, at doses of 1 and 5 μg/rat, was injected bilaterally into the BLA five minutes prior to injecting formalin. Following the injection, the pain and inflammation of the paws were measured using Dubbison-Dennis and mercury immersion methods, respectively. The behavior of the animals, including licking time and foot volume, was assessed. RESULTS： The results showed that the inactivation of the NMDA receptors in the BLA in the acute phase of pain reduced the licking time （the emotional aspect of pain）. However, at a high dose （5μg/rat）, memantine exacerbates the pain induced by formalin in the chronic phase. Additionally, the inhibition of the NMDA receptors in the BLA by memantine enhanced the formalin-induced increase in foot volume （inflammation） in a dose-dependent manner. CONCLUSION： The study showed that the NMDA glutamate receptors in the BLA are crucial for the emotional pain and inflammation in both chronic and acute phases of formalin-induced pain. However, their roles are more pronounced in the chronic phase than in the acute phase of pain.展开更多
The psychostimulant methylphenidate (MPD; also called Ritalin) is a blocker of dopamine and norepi-nephrine transporter. It has been clinically used for treatment of Attention Deficit and Hyperactivity Disorder (ADHD)...The psychostimulant methylphenidate (MPD; also called Ritalin) is a blocker of dopamine and norepi-nephrine transporter. It has been clinically used for treatment of Attention Deficit and Hyperactivity Disorder (ADHD). There have been inconsistent reports regarding the effects of systemically adminis-tered MPD on learning and memory, either in animals or humans. In the present study, we investigated the effect of direct infusion of MPD into the basolateral nucleus of amygdala (BLA) or the anterior cin-gulate cortex (ACC) on conditioned fear memory. Rats were trained on a one-trial step-through inhibi-tory avoidance task. MPD was infused bilaterally into the BLA or the ACC, either at ‘0’ or 6 h post-training. Saline was administered as control. Memory retention was tested 48 h post-training. In-tra-BLA or intra-ACC infusion of MPD ‘0’ h but not 6 h post-training significantly improved 48-h memory retention: the MPD-treated rats had significant longer step-through latency than controls. The present results indicate that action of MPD in the BLA or the ACC produces a beneficial effect on the consoli-dation of inhibitory avoidance memory.展开更多
Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing situations.Based on the behavioral hypothesis that...Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing situations.Based on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear memory.The brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain unclear.Intriguing questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction memory.In this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.展开更多
AIM:To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.METHODS:The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied.Para...AIM:To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.METHODS:The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied.Paracellular hyperpermeability was induced in Caco2.BBE and HT-29CL.19A cell lines by adding phorbol-12,13-dibutyrate(PDB) apically,after which the effects of glutamine and glutamate on horseradish peroxidase(HRP) diffusion were studied.An inhibitor of glutamate transport(L-trans-pyrrolidine-2,4-dicarboxylic acid:trans-PDC) and an irreversible blocker(acivicin) of the extracellular glutamine to glutamate converting enzyme,γ-glutamyltransferase,were used.RESULTS:Apical to basolateral HRP flux increased significantly compared to controls not exposed to PDB (n=30,P<0.001).Glutamine application reduced hyperpermeability by 19%and 39%in the respective cell lines.Glutamate application reduced hyperpermeability by 30%and 20%,respectively.Incubation of HT29CL.19A cells with acivicin and subsequent PDB and glutamine addition increased permeability levels.Incubation of Caco2.BBE cells with trans-PDC followed by PDB and glutamate addition also resulted in high permeability levels.CONCLUSION:Apical glutamate-similar to glutaminecan decrease induced paracellular hyperpermeability.Extracellular conversion of glutamine to glutamate and subsequent uptake of glutamate could be a pivotal step in the mechanism underlying the protective effect of glutamine.展开更多
The amygdala,which is involved in various behaviors and emotions,is reported to connect with the whole brain.However,the long-range inputs of distinct cell types have not yet been defined.Here,we used a retrograde tra...The amygdala,which is involved in various behaviors and emotions,is reported to connect with the whole brain.However,the long-range inputs of distinct cell types have not yet been defined.Here,we used a retrograde trans-synaptic rabies virus to generate a whole-brain map of inputs to the main cell types in the mouse amygdala.We identified 37 individual regions that projected to neurons expressing vesicular glutamate transporter 2,78 regions to parvalbumin-expressing neurons,104 regions to neurons expressing protein kinase C-δ,and 89 regions to somatostatin-expressing neurons.The amygdala received massive projections from the isocortex and striatum.Several nuclei,such as the caudate-putamen and the CA1 field of the hippocampus,exhibited input preferences to different cell types in the amygdala.Notably,we identified several novel input areas,including the substantia innominata and zona incerta.These findings provide anatomical evidence to help understand the precise connections and diverse functions of the amygdala.展开更多
The influence of γ-aminobutyric type-A (GABA<sub>A</sub>) receptors agonist (muscimol hydrobromide, 0.1 μg/0.5 μl) injections into the right or left basolateral amygdala (BLA) on the behavior of high-an...The influence of γ-aminobutyric type-A (GABA<sub>A</sub>) receptors agonist (muscimol hydrobromide, 0.1 μg/0.5 μl) injections into the right or left basolateral amygdala (BLA) on the behavior of high-anxiety (HA) and low-anxiety (LA) rats subjected to the elevated plus-maze (EPM) test was investigated. Anxiolytic-like effects (increase of open-arm entries and open-arm time) was revealed only after administration of muscimol into the left (but not right) amygdala of HA animals. No effect was observed upon administration of muscimol to LA rats. These findings suggest an important role in anxiety regulation of the amygdalar GABA levels, and the assumed GABA hemispheric lateralization.展开更多
基金supported by the National Natural Science Foundation of China,Nos.32371070 (to JT),31761163005 (to JT),32100824 (to QX)the Shenzhen Science and Technology Program,Nos.RCBS20210609104606024 (to QX),JCY20210324101813035 (to DL)+4 种基金the Guangdong Provincial Key S&T Program,No.2018B030336001 (to JT)the Key Basic Research Program of Shenzhen Science and Technology Innovation Commission,Nos.JCYJ20200109115405930 (to JT),JCYJ20220818101615033 (to DL),JCYJ20210324115811031 (to QX),JCYJ20200109150717745 (to QX)Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases,No.ZDSYS20220304163558001 (to JT)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,No.2023B1212060055 (to JT)the China Postdoctoral Science Foundation,No.2021M693298 (to QX)。
文摘The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.
基金supported by the National Natural Science Foundation of China,Nos.32371065(to CL)and 32170950(to LY)the Natural Science Foundation of the Guangdong Province,No.2023A1515010899(to CL)the Science and Technology Projects in Guangzhou,Nos.2023A4J0578 and 2024A03J0180(to CW)。
文摘Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.
基金supported by the STI 2030—Major Projects 2021ZD0204000,No.2021ZD0204003 (to XZ)the National Natural Science Foundation of China,Nos.32170973 (to XZ),32071018 (to ZH)。
文摘Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.
基金supported by grants from the National Natural Science Foundation of China(31970902,U22A20306,and 3192010300)the Municipal Administration of Hospitals Incubating Program(PZ2023009)+1 种基金the Key-Area R&D Program of Guangdong Province(2019B030335001)the Autism Research Special Fund of Zhejiang Foundation for Disabled Persons(2022003).
文摘Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivity of basolateral amygdala(BLA)pyramidal neurons(PNs)in Shank3 InsG3680 knock-in(InsG3680+/+)mice is involved in the development of anxiety.Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs.Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+mice.Further study found that the diminished control of the BLA by medial prefrontal cortex(mPFC)and optogenetic activation of the mPFC-BLA pathway also had a rescue effect,which increased the feedforward inhibition of the BLA.Taken together,our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+mice.
基金supported by the China Postdoctoral Science Foundation(No.2023M740731)Fundamental Research Funds for the Central Universities(No.SWU-KQ22024)+2 种基金National Key Research and Development Program of China(No.2021YFD1800900)National Natural Science Foundation of China(No.82073790)the Chongqing Science and Technology Commission(No.CSTB2022TIAD-LUX0001)。
文摘In polarized cells,the differential distribution of proteins results in the formation of apical and basolateral membranes.The basolateral membrane contacts basal lamina and mediates cell-to-cell communication,which is crucial for maintaining homeostasis and enabling drug absorption.To establish and maintain the basolateral domain,intricate mechanisms are necessary to ensure the proper sorting and transportation of molecules.Sorting signals play a crucial role in regulating the distributions of basolateral proteins,determining their trafficking route and final residence.Newly synthesized proteins can be segregated into different carrier vesicles at either trans-Golgi network(TGN)or endosomes.Additionally,understanding basolateral transport in polarized epithelial cells is important for predicting diseases and delivering drugs.This review provides a summary of recent advancements in the mechanisms and applications of basolateral sorting and trafficking.
基金supported by the Shahid Chamran University of Ahvaz,Iran
文摘In this study we investigated whether GABAA receptors of the basolateral amygdala(BLA) interact with the effect of dexamethasone on the retrieval stage of memory.Adult male Wistar rats were bilaterally cannulated in the BLA by stereotaxic surgery.The animals were trained in step-through apparatus by induction of electric shock(1.5 mA,3 s) and were tested for memory retrieval after 1 d.The time of latency for entering the dark compartment of the instrument and the time spent by rats in this chamber were recorded for evaluation of the animals' retrieval in passive avoidance memory.Administration of dexamethasone(0.3 and 0.9 mg/kg,subcutaneously(s.c.)),immediately after training,enhanced memory retrieval.This effect was reduced by intra-BLA microinjection of muscimol(0.125,0.250 and 0.500 μg/rat),when administered before 0.9 mg/kg of dexamethasone.Microinjection of bicuculline(0.75 μg/rat,intra-BLA) with an ineffective dose of dexamethasone(0.1 mg/kg,s.c.) increased memory retrieval.However,the same doses of muscimol and bicuculline without dexamethasone did not affect memory processes.Our data support reports that dexamethasone enhances memory retrieval.It seems that GABAA receptors of the BLA mediate the effect of dexamethasone on memory retrieval in rats.
文摘This study was aimed to determine the effect of amygdaline inactivation on the sexual motivation of male rats during a T-maze task with a sexual reward. Subjects were chronically implanted with two stainless-steel cannulae that enabled the infusion of tetrodotoxin, a sodium channel blocker, into the left and right basolateral amygdala (BLA). Animals were divided into 3 groups: saline (SS);TTX1 (tetrodotoxin at 2.5 ng);and TTX2 (tetrodotoxin at 5.0 ng). To induce a sexually-motivated state, all male rats were allowed to have an intromission with a receptive female before performing the T-maze task, after which their sexual motivation was evaluated during seven trials in which a receptive female was placed in one goal-box of the T-maze, and a non-receptive one in the other. Subjects were allowed an intromission as a sexual reward whenever they reached the goal-box containing the receptive female, but were returned to the start-box if they did not. At the end of the experiment, copulation until ejaculation was permitted. Both doses of TTX increased the time rats required to cross the maze stem during the final trials. In terms of sexual interaction, the high dose of TTX increased more markedly mount, intromission and ejaculation latencies and the number of mounts and intromissions. Overall, these results indicate that the BLA may play an important role in modulating sexual behavior, particularly in maintaining sexual motivation in successive trials in a T-maze task and during sexual interaction per se.
基金Supported by the Natural Science Foundation of Anhui Province(Nos.2108085QH332,2408085MH189)the CHEN Hao's Famous Traditional Chinese Pharmacist Studio of Anhui Province,the Scientific Research Project of Colleges and Universities in Anhui Province(Nos.2024AH051017,KJ2021A0202)+2 种基金the Education Department of Anhui Province Young and Middle-Aged Talent Cultivation Project(No.YQYB2024031)the Students'Innovation and Entrepreneurship Training Program of Anhui Province(No.S202410366078)the Scientific Research Platform and Base Upgrading Plan of Anhui Medical University(No.2021xkjT048)。
文摘Objective:To elucidate the modulation mechanism of Suanzaoren Decoction(SZRD)on basolateral amygdala(BLA)neuronal activity to alleviate chronic restraint stress(CRS)-related behavioral deficits.Methods:The male C57BL/6J mice were assigned to 4 groups using the complete randomization method,including control(CON,n=19),CRS(n=19),SZRD(n=21),and fluoxetine(Flu,n=22)groups.Mice were restrained for 6 h per day,over a 21-d period to establish CRS models.The CON group remained in their cages without food or water during the 6-h matching period.SZRD and Flu groups received intragastric administration of SZRD(4.68 g/kg)and Flu(20 mg/kg)daily,respectively,30 min before restraint for 21 consecutive days.The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test,elevated plus maze test,and forced swimming test.The cellular Fletcher B.Judson murine osteosarcoma proto-oncogene(c-Fos)expression in the BLA was measured using immunofluorescence,while action potential(AP)firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings.Results:SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time(P<0.05or P<0.01).It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA(P<0.01).Additionally,SZRD selectively attenuated excitatory(P<0.01),but not inhibitory,synaptic transmission onto BLA pyramidal neurons.Conclusion:SZRD alleviated CRS-induced anxiety-and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
基金sponsored by the National Natural Science Foundation of China(Nos.61960206012,T2293730,T2293731,62121003,62171434,62333020,62374004,81971348,and 61673024)the National Key Research and Development Program of China(Nos.2022YFB3205602 and 2022YFC2402501)Major Program of Scientific and Technical Innovation 2030(No.2021ZD02016030).
文摘Depression is a common and severely debilitating neuropsychiatric disorder.Multiple studies indicate a strong correlation between the occurrence of immunological inflammation and the presence of depression.The basolateral amygdala(BLA)is crucial in the cognitive and physiological processing and control of emotion.However,due to the lack of detection tools,the neural activity of the BLA during depression is not well understood.In this study,a microelectrode array(MEA)based on the shape and anatomical location of the BLA in the brain was designed and manufactured.Rats were injected with lipopolysaccharide(LPS)for 7 consecutive days to induce depressive behavior.We used the MEA to detect neural activity in the BLA before modeling,during modeling,and after LPS administration on 7 consecutive days.The results showed that after LPS treatment,the spike firing of neurons in the BLA region of rats gradually became more intense,and the local field potential power also increased progressively.Further analysis revealed that after LPS administration,the spike firing of BLA neurons was predominantly in the theta rhythm,with obvious periodic firing characteristics appearing after the 7 d of LPS administration,and the relative power of the local field potential in the theta band also significantly increased.In summary,our results suggest that the enhanced activity of BLA neurons in the theta band is related to the depressive state of rats,providing valuable guidance for research into the neural mechanisms of depression.
基金National Natural Science Foundation of China(82373860 and 82071202 to Susu Tang,82173805 to Hao Hong)National Innovation and Entrepreneurship Training Program for Undergraduate(202410316198,China).
文摘Anxiety disorders are one of the most epidemic and chronic psychiatric disorders.An incom-plete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders.GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders.However,no study has investigated the role of GPR17 in psychiatric disorders.In a well-established chronic restraint stress(CRS)mouse model,using a combination of pharmacological and molecular biology techniques,viral tracing,in vitro electrophysiology recordings,in vivo fiber photom-etry,chemogenetic manipulations and behavioral tests,we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala(BLA)glutamatergic neurons.Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutama-tergic neurons effectively improved anxiety-like behaviors.Overexpression of GPR17 in BLA glutama-tergic neurons increased the susceptibility to anxiety-like behaviors.What's more,BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors via BLA to ventral hippocampal CAl glutamatergic projection.Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders.
文摘The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts in the urine.Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced,as seen in familial renal glycosuria(FRG).FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene,which encodes the sodium-glucose cotransporter(SGLT)2.Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes,and since FRG is often considered an asymptomatic and benign condition,it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes.However,patients with FRG may exhibit clinical features such as lower body weight or height,altered systemic blood pressure,diaper dermatitis,amino-aciduria,decreased serum uric acid levels,and hypercalciuria.Further research is needed to fully understand the pathophysiology,molecular genetics,and clinical manifestations of renal glucosuria.
文摘Background Glucocorticoid receptor （GR） is believed to be a major factor in brain maturation and in modulation of a series of brain activity. Hippocampal neurons are abundant in glucocorticoid receptor, and there is significant change in GR expression under certain pathological state. Epilepsy is a special pathological state of the central nervous system. This study aimed to explore the role of GR in epilepsy by observing the change and functions of GR in hippocampus with a basolateral amygdale-electrical kindled rat epilepsy model. Methods Firstly, we established the basolateral amygdale-electrical kindled rat epilepsy model. Then GR mRNA expression in the hippocampus was assayed by semi-quantitative reverse transcription-PCR in this experiment. In addition, the processes of epileptic seizures were observed and electroencephalograms were recorded. One-way analysis of variance （ANOVA） was employed for comparing means of multiple groups, followed Fisher＇s least significant difference （LSD） for paired comparison. Results The rats were successfully kindled after an average of （13.50＋3.99） times electrical stimulation, in which it was showed that GR mRNA expression reduced obviously as compared with the control group and the sham groups （P 〈0.001）. The down-regulation of GR mRNA expression was abated or reversed by some anti-epilepsy drugs （P 〈0.001 compared with the epilepsy group）, accompanied by attenuation of seizures and improvement of electroencephalograms. Conclusions Down-regulation of hippocampal GR mRNA expression may be related to the kindling. Anti-epilepsy drugs exposure can retard this change.
文摘BACKGROUND： The role of the amygdala in controlling emotional pain has been emphasized in several studies. In this study, the role of the NMDA glutamate receptors in the basolateral nucleus of the amygdala （BLA） in regulating inflammation and emotional pain, induced by formalin, was studied in male rats. METHODS： Male Wistar rats, weighing 250±0 g, were injected with 20 μL of 2% formalin into the paw of the right hind limb. Memantine, at doses of 1 and 5 μg/rat, was injected bilaterally into the BLA five minutes prior to injecting formalin. Following the injection, the pain and inflammation of the paws were measured using Dubbison-Dennis and mercury immersion methods, respectively. The behavior of the animals, including licking time and foot volume, was assessed. RESULTS： The results showed that the inactivation of the NMDA receptors in the BLA in the acute phase of pain reduced the licking time （the emotional aspect of pain）. However, at a high dose （5μg/rat）, memantine exacerbates the pain induced by formalin in the chronic phase. Additionally, the inhibition of the NMDA receptors in the BLA by memantine enhanced the formalin-induced increase in foot volume （inflammation） in a dose-dependent manner. CONCLUSION： The study showed that the NMDA glutamate receptors in the BLA are crucial for the emotional pain and inflammation in both chronic and acute phases of formalin-induced pain. However, their roles are more pronounced in the chronic phase than in the acute phase of pain.
基金Supported by the Ministry of Science and Technology of China(Grant Nos.2006CB500807 and 2006AA02Z199)the Ministry of Education of China(Program for Changjiang Scholars and Innovative Research Team in University)the National Natural Science Foundation of China(Grant Nos.30225023,30430240 and 30611120530)
文摘The psychostimulant methylphenidate (MPD; also called Ritalin) is a blocker of dopamine and norepi-nephrine transporter. It has been clinically used for treatment of Attention Deficit and Hyperactivity Disorder (ADHD). There have been inconsistent reports regarding the effects of systemically adminis-tered MPD on learning and memory, either in animals or humans. In the present study, we investigated the effect of direct infusion of MPD into the basolateral nucleus of amygdala (BLA) or the anterior cin-gulate cortex (ACC) on conditioned fear memory. Rats were trained on a one-trial step-through inhibi-tory avoidance task. MPD was infused bilaterally into the BLA or the ACC, either at ‘0’ or 6 h post-training. Saline was administered as control. Memory retention was tested 48 h post-training. In-tra-BLA or intra-ACC infusion of MPD ‘0’ h but not 6 h post-training significantly improved 48-h memory retention: the MPD-treated rats had significant longer step-through latency than controls. The present results indicate that action of MPD in the BLA or the ACC produces a beneficial effect on the consoli-dation of inhibitory avoidance memory.
基金supported by grants from the STI2030-Major Projects(2021ZD0202800)the National Natural Science Foundation of China(32071023 and 32371078)+2 种基金the Program of Shanghai Academic/Technology Research Leader(22XD1420700)the Shanghai Municipal Health Commission(2022XD046)Innovative Research Team of High-Level Local Universities in Shanghai.
文摘Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing situations.Based on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear memory.The brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain unclear.Intriguing questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction memory.In this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.
基金Supported by VU University Medical Center,Amsterdam,The Netherlands
文摘AIM:To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.METHODS:The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied.Paracellular hyperpermeability was induced in Caco2.BBE and HT-29CL.19A cell lines by adding phorbol-12,13-dibutyrate(PDB) apically,after which the effects of glutamine and glutamate on horseradish peroxidase(HRP) diffusion were studied.An inhibitor of glutamate transport(L-trans-pyrrolidine-2,4-dicarboxylic acid:trans-PDC) and an irreversible blocker(acivicin) of the extracellular glutamine to glutamate converting enzyme,γ-glutamyltransferase,were used.RESULTS:Apical to basolateral HRP flux increased significantly compared to controls not exposed to PDB (n=30,P<0.001).Glutamine application reduced hyperpermeability by 19%and 39%in the respective cell lines.Glutamate application reduced hyperpermeability by 30%and 20%,respectively.Incubation of HT29CL.19A cells with acivicin and subsequent PDB and glutamine addition increased permeability levels.Incubation of Caco2.BBE cells with trans-PDC followed by PDB and glutamate addition also resulted in high permeability levels.CONCLUSION:Apical glutamate-similar to glutaminecan decrease induced paracellular hyperpermeability.Extracellular conversion of glutamine to glutamate and subsequent uptake of glutamate could be a pivotal step in the mechanism underlying the protective effect of glutamine.
基金the Key Project of the National Natural Science Foundation of China(31430034)the National Key Research and Development Project of the Ministry of Science and Technology of China(2016YF051000)+3 种基金the Science and Technology Program of Guangdong Province,China(2018B030334001)the Key Realm R&D Program of Guangdong Province,China(2019B030335001)Funds for Creative Research Groups of China from the National Natural Science Foundation of China(81521062)the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2019PT310023)。
文摘The amygdala,which is involved in various behaviors and emotions,is reported to connect with the whole brain.However,the long-range inputs of distinct cell types have not yet been defined.Here,we used a retrograde trans-synaptic rabies virus to generate a whole-brain map of inputs to the main cell types in the mouse amygdala.We identified 37 individual regions that projected to neurons expressing vesicular glutamate transporter 2,78 regions to parvalbumin-expressing neurons,104 regions to neurons expressing protein kinase C-δ,and 89 regions to somatostatin-expressing neurons.The amygdala received massive projections from the isocortex and striatum.Several nuclei,such as the caudate-putamen and the CA1 field of the hippocampus,exhibited input preferences to different cell types in the amygdala.Notably,we identified several novel input areas,including the substantia innominata and zona incerta.These findings provide anatomical evidence to help understand the precise connections and diverse functions of the amygdala.
文摘The influence of γ-aminobutyric type-A (GABA<sub>A</sub>) receptors agonist (muscimol hydrobromide, 0.1 μg/0.5 μl) injections into the right or left basolateral amygdala (BLA) on the behavior of high-anxiety (HA) and low-anxiety (LA) rats subjected to the elevated plus-maze (EPM) test was investigated. Anxiolytic-like effects (increase of open-arm entries and open-arm time) was revealed only after administration of muscimol into the left (but not right) amygdala of HA animals. No effect was observed upon administration of muscimol to LA rats. These findings suggest an important role in anxiety regulation of the amygdalar GABA levels, and the assumed GABA hemispheric lateralization.
