Engrams, which are cellular substrates of memory traces, have been identified in various brain areas, including the amygdala. While most identified engrams are composed of excitatory, glutamatergic neurons, GABAergic inhibitory engrams have been relatively overlooked. Here, we report the identification of an inhibitory engram in the central lateral amygdala (CeL), a key area for auditory fear conditioning. This engram is primarily composed of GABAergic somatostatin-expressing (SST(+)) and, to a lesser extent, protein kinase C-δ-expressing (PKC-δ(+)) neurons. Fear memory is accompanied by a preferential enhancement of synaptic inhibition onto PKC-δ(+) neurons. Silencing this CeL GABAergic engram disinhibits the activity of targeted extra-amygdaloid areas, selectively increasing the expression of fear. Our findings define the behavioral function of an engram formed exclusively by GABAergic inhibitory neurons in the mammalian brain.
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http://dx.doi.org/10.1016/j.celrep.2024.114468 | DOI Listing |
Cells
December 2024
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), Institute of Mental Health and Drug Discovery, School of Mental Health, Wenzhou Medical University, Ouhai District, Wenzhou 325000, China.
Background: glucocorticoids may play an important role in the formation of fear memory, which is relevant to the neurobiology of post-traumatic stress disorder (PTSD). In our previous study, we showed the glucocorticoid receptor (GR) forms a protein complex with FKBP51, which prevents translocation of GR into the nucleus to affect gene expression; this complex is elevated in PTSD patients and by fear-conditioned learning in mice, and disrupting this complex blocks the storage and retrieval of fear-conditioned memories. The timing of release of glucocorticoid relative to the formation of a traumatic memory could be important in this process, and remains poorly understood.
View Article and Find Full Text PDFBiomedicines
December 2024
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA.
Alzheimer's disease (AD) is marked by amyloid-β plaques and hyperphosphorylated tau neurofibrillary tangles (NFTs), leading to cognitive decline and debilitating non-cognitive symptoms. This study aimed to evaluate compounds from four different classes in a short-term (7-day) study using transgenic tau mice to assess their ability to reduce non-cognitive symptoms. The best candidate was then evaluated for longer exposure to assess non-cognitive symptoms, cognition, and pathology.
View Article and Find Full Text PDFBiomedicines
November 2024
State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Background/objectives: Levo-Stepholidine (-SPD), a compound extracted from Chinese herbs, has the potential to treat psychotic disorders where cognitive deficits are a critical challenge. -SPD displays a D1R agonism/D2R antagonism pharmacological profile, and its effect on cognitive function is still vague and lacks comprehensive study. Here, we investigated the impact of l-SPD on two core indexes of executive function, working memory and response inhibition, and learning and memory.
View Article and Find Full Text PDFBrain Sci
December 2024
Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal 59078-900, Brazil.
Background/objectives: Recent studies have investigated the effects of ketamine on fear memory in animals. However, it is unclear if ketamine might affect avoidance memory and emotional behaviors concomitantly. In this study, we compared the effects of (,)- and ()-ketamine in modulating avoidance responses, depression- and anxiety-related behaviors in stressed mice.
View Article and Find Full Text PDFBrain Sci
December 2024
Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA.
Background/objectives: Rodents provide a useful translational model of fear- and anxiety-related behaviors. Previously stressed animals exhibit physiological and behavioral stress responses that parallel those observed in anxious humans. Patients diagnosed with post-traumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms that result from exposure to one or more traumatic events, with individuals exposed to early adverse experiences and women having increased vulnerability for diagnoses; however, the mechanisms of this increased vulnerability remain unknown.
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