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:The amygdala is known to modulate hippocampal synaptic plasticity. One role could be an immediate effect of basolateral amygdala (BLA) in priming synaptic plasticity in the hippocampus. Another role could be through associative synaptic co-operation and competition that triggers events involved in the maintenance of synaptic potentiation. We present evidence that the timing and activity level of BLA stimulation are important factors for the induction and maintenance of long-term potentiation (LTP) in ventral hippocampal area CA1. A 100 Hz BLA co-stimulation facilitated the induction of LTP, whereas 200 Hz co-stimulation attenuated induction. A 100 Hz BLA co-stimulation also caused enhanced persistence, sufficient to prevent synaptic competition. This maintenance effect is likely through translational mechanisms, as mRNA expression of primary response genes was unaffected, whereas protein level of plasticity-related products was increased. Further understanding of the neural mechanisms of amygdala modulation on hippocampus could provide insights into the mechanisms of emotional disorders.
Project description:Chronic social isolation stress during adolescence induces susceptibility for neuropsychiatric disorders. Here we show that 5-week post-weaning isolation stress induces sex-specific behavioral abnormalities and neuronal activity changes in the prefrontal cortex (PFC), basal lateral amygdala (BLA), and ventral tegmental area (VTA). Chemogenetic manipulation, optogenetic recording, and in vivo calcium imaging identify that the PFC to BLA pathway is causally linked to heightened aggression in stressed males, and the PFC to VTA pathway is causally linked to social withdrawal in stressed females. Isolation stress induces genome-wide transcriptional alterations in a region-specific manner. Particularly, the upregulated genes in BLA of stressed males are under the control of activated transcription factor CREB, and CREB inhibition in BLA normalizes gene expression and reverses aggressive behaviors. On the other hand, neuropeptide Hcrt (Hypocretin/Orexin) is among the top-ranking downregulated genes in VTA of stressed females, and Orexin-A treatment rescues social withdrawal. These results have revealed molecular mechanisms and potential therapeutic targets for stress-related mental illness.
2022-03-22 | GSE198725 | GEO
Project description:Bla NDM5 Klebsiella pneumoniae Tanzania
Project description:We performed single cell transcriptomics analyses in medial prefrontal cortical (mPFC) and basolateral amygdala (BLA). Ketamine induced changes in inflammatory pathways reversing corticosterone effects. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling is decreased after corticosterone but increased following ketamine administration in excitatory neurons. Single cell transcriptomics analyses in dorsolateral prefrontal cortical (dl-PFC) neurons of depressed patients also showed decreased PCP signaling in excitatory neurons. Using chemogenetics, we found that the BLA-projecting infra limbic prefrontal cortex (IL PFC) neurons regulate immobility time in the tail suspension test and food consumption. Using RNAScope, we found, in the excitatory neurons in mPFC, Celsrs and Prickle2 were reduced by corticosterone but increased by ketamine. Using CRISPR-Cas9, we conditionally knocked out Celsrs and Prickle2 in the BLA-projecting IL-PFC neurons and found that ketamine-induced synapse restoration and behavioral remission were abolished. Ketamine affects gene expression and PCP proteins underly long-lasting effects of low-dose ketamine.