Project description:The basolateral amygdala (BLA) contains discrete neuronal circuits that integrate positive or negative emotional information and drive the appropriate innate and learned behaviors. Whether how these circuits consist of genetically-identifiable and anatomically segregated neuron types, is currently poorly understood. Also, our understanding of the response patterns and behavioral spectra of genetically-identifiable BLA neurons is limited. Here, we classified 11 glutamatergic BLA cell types having topography in BLA. Several clusters were enriched in lateral versus basal amygdala, others were enriched in either anterior or posterior regions of the BLA. Two of these BLA subpopulations innately responded to valence-specific stimuli, whereas one represented to both aversive and social cues. Positive-valence BLA neurons promoted normal feeding, while mixed selectivity neurons promoted fear learning and social interactions. These findings enhance our understanding of cell type diversity and spatial organization of the BLA and the role of distinct BLA populations in representing valence-specific and mixed stimuli.
Project description:It is known that the eCB 2-AG is synthesized in postsynaptic cells and released into synaptic clefts when needed. As we observed that acute stress prominently increased eCBs in vmPFC-BLA synapses and that inhibited expression of 2-AG synthase gene Dagla in vmPFC-BLA synapses blocked stress-induced PGCID, we plausibly hypothesized that transient GCI increased 2-AG biosynthesis in BLA neurons, leading to stress-induced increase of 2-AG release into vmPFC-BLA synapses. To test this hypothesis, we employed single-cell sequencing to examine whether GCI mice, in comparison with sham mice, showed increased mRNA expression of the Dagla in c-fos positive BLA and vmPFC cells of acute stress-treated mice
Project description:In order to identify specific transcripts that might be necessary for CTA learning within the BLA, we used cell type-specific RNA-seq to profile transcriptional changes in sorted BLA projection neurons 4 hours following training.
Project description:The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Different neuronal populations of the basolateral amygdala complex (BLA) encode fearful or rewarding associations, but the molecular identity of these functionally distinct populations of BLA neurons remained unknown. Here, we show that BLA neurons projecting to the nucleus accumbens (NAc-projectors) or the centromedial amygdala (CeM-projectors) underwent opposing synaptic changes following fear or reward conditioning. The photostimulation of NAc projectors supported positive reinforcement while photostimulation of CeM projectors mediated negative reinforcement. In search of defining molecular characteristics of these functionally-distinct BLA neuronal populations, we compared gene expression profiles of NAc- and CeM-projectors.
Project description:The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Different neuronal populations of the basolateral amygdala complex (BLA) encode fearful or rewarding associations, but the molecular identity of these functionally distinct populations of BLA neurons remained unknown. Here, we show that BLA neurons projecting to the nucleus accumbens (NAc-projectors) or the centromedial amygdala (CeM-projectors) underwent opposing synaptic changes following fear or reward conditioning. The photostimulation of NAc projectors supported positive reinforcement while photostimulation of CeM projectors mediated negative reinforcement. In search of defining molecular characteristics of these functionally-distinct BLA neuronal populations, we compared gene expression profiles of NAc- and CeM-projectors. For comparison of gene expression profiles of NAc- and CeM-projectors, we conducted two independent RNA sequencing experiments. In experiment-1, a total of n=9 samples (n=4 NAc- and n=5 CeM-projectors) are analyzed. In experiment-2, a total of n=8 samples (n=4 NAc- and n=4 CeM-projectors) are analyzed.
Project description:Astrocytes tile the central nervous system (CNS) and have fundamental roles in physiology and disease, yet there remain open questions about their contributions to physiological and pathological processes in the CNS. The basolateral amygdala (BLA) integrates rewarding and aversive stimuli and is integral to mood regulation and emotional behaviors. As many past studies have focused on neurons in the BLA, the contribution of BLA astrocytes to emotional behaviors is largely unknown. A major bottleneck has been the paucity of reliable tools to explore astrocyte functions and molecular mechanisms in vivo. This shortfall has been addressed by recent developments in the field reporting approaches to systematically explore the role of astrocytes with improved tools. Here, we used several such tools to elucidate BLA astrocytic changes during emotional behavioral responses. Applying several mouse models of stress (negative emotional triggers) and astrocyte-specific adenoassociated viruses (AAVs), [Ca2+] imaging, RNA sequencing, and proteomics, we explored the role of astrocytes at the molecular and cellular level in the BLA. We analyzed the data to evaluate how astrocytes might be exploited in vivo to improve behavioral outcomes in emotion-related disorders such as anxiety and depression.
Project description:Astrocytes tile the central nervous system (CNS) and have fundamental roles in physiology and disease, yet there remain open questions about their contributions to physiological and pathological processes in the CNS. The basolateral amygdala (BLA) integrates rewarding and aversive stimuli and is integral to mood regulation and emotional behaviors. As many past studies have focused on neurons in the BLA, the contribution of BLA astrocytes to emotional behaviors is largely unknown. A major bottleneck has been the paucity of reliable tools to explore astrocyte functions and molecular mechanisms in vivo. This shortfall has been addressed by recent developments in the field reporting approaches to systematically explore the role of astrocytes with improved tools. Here, we used several such tools to elucidate BLA astrocytic changes during emotional behavioral responses. Applying several mouse models of stress (negative emotional triggers) and astrocyte-specific adenoassociated viruses (AAVs), [Ca2+] imaging, RNA sequencing, and proteomics, we explored the role of astrocytes at the molecular and cellular level in the BLA. We analyzed the data to evaluate how astrocytes might be exploited in vivo to improve behavioral outcomes in emotion-related disorders such as anxiety and depression.
Project description:Astrocytes tile the central nervous system (CNS) and have fundamental roles in physiology and disease, yet there remain open questions about their contributions to physiological and pathological processes in the CNS. The basolateral amygdala (BLA) integrates rewarding and aversive stimuli and is integral to mood regulation and emotional behaviors. As many past studies have focused on neurons in the BLA, the contribution of BLA astrocytes to emotional behaviors is largely unknown. A major bottleneck has been the paucity of reliable tools to explore astrocyte functions and molecular mechanisms in vivo. This shortfall has been addressed by recent developments in the field reporting approaches to systematically explore the role of astrocytes with improved tools. Here, we used several such tools to elucidate BLA astrocytic changes during emotional behavioral responses. Applying several mouse models of stress (negative emotional triggers) and astrocyte-specific adenoassociated viruses (AAVs), [Ca2+] imaging, RNA sequencing, and proteomics, we explored the role of astrocytes at the molecular and cellular level in the BLA. We analyzed the data to evaluate how astrocytes might be exploited in vivo to improve behavioral outcomes in emotion-related disorders such as anxiety and depression.
Project description:Astrocytes tile the central nervous system (CNS) and have fundamental roles in physiology and disease, yet there remain open questions about their contributions to physiological and pathological processes in the CNS. The basolateral amygdala (BLA) integrates rewarding and aversive stimuli and is integral to mood regulation and emotional behaviors. As many past studies have focused on neurons in the BLA, the contribution of BLA astrocytes to emotional behaviors is largely unknown. A major bottleneck has been the paucity of reliable tools to explore astrocyte functions and molecular mechanisms in vivo. This shortfall has been addressed by recent developments in the field reporting approaches to systematically explore the role of astrocytes with improved tools. Here, we used several such tools to elucidate BLA astrocytic changes during emotional behavioral responses. Applying several mouse models of stress (negative emotional triggers) and astrocyte-specific adenoassociated viruses (AAVs), [Ca2+] imaging, RNA sequencing, and proteomics, we explored the role of astrocytes at the molecular and cellular level in the BLA. We analyzed the data to evaluate how astrocytes might be exploited in vivo to improve behavioral outcomes in emotion-related disorders such as anxiety and depression.