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1.
PLoS Biol ; 21(6): e3002154, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37289847

RESUMO

Fear-related memory traces are encoded by sparse populations of hippocampal principal neurons that are recruited based on their inhibitory-excitatory balance during memory formation. Later, the reactivation of the same principal neurons can recall the memory. The details of this mechanism are still unclear. Here, we investigated whether disinhibition could play a major role in this process. Using optogenetic behavioral experiments, we found that when fear was associated with the inhibition of mouse hippocampal somatostatin positive interneurons, the re-inhibition of the same interneurons could recall fear memory. Pontine nucleus incertus neurons selectively inhibit hippocampal somatostatin cells. We also found that when fear was associated with the activity of these incertus neurons or fibers, the reactivation of the same incertus neurons or fibers could also recall fear memory. These incertus neurons showed correlated activity with hippocampal principal neurons during memory recall and were strongly innervated by memory-related neocortical centers, from which the inputs could also control hippocampal disinhibition in vivo. Nonselective inhibition of these mouse hippocampal somatostatin or incertus neurons impaired memory recall. Our data suggest a novel disinhibition-based memory mechanism in the hippocampus that is supported by local somatostatin interneurons and their pontine brainstem inputs.


Assuntos
Interneurônios , Memória , Camundongos , Animais , Interneurônios/metabolismo , Memória/fisiologia , Hipocampo/metabolismo , Medo/fisiologia , Somatostatina/metabolismo
2.
Science ; 366(6469)2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31780530

RESUMO

Adverse events need to be quickly evaluated and memorized, yet how these processes are coordinated is poorly understood. We discovered a large population of excitatory neurons in mouse median raphe region (MRR) expressing vesicular glutamate transporter 2 (vGluT2) that received inputs from several negative experience-related brain centers, projected to the main aversion centers, and activated the septohippocampal system pivotal for learning of adverse events. These neurons were selectively activated by aversive but not rewarding stimuli. Their stimulation induced place aversion, aggression, depression-related anhedonia, and suppression of reward-seeking behavior and memory acquisition-promoting hippocampal theta oscillations. By contrast, their suppression impaired both contextual and cued fear memory formation. These results suggest that MRR vGluT2 neurons are crucial for the acquisition of negative experiences and may play a central role in depression-related mood disorders.


Assuntos
Agressão/fisiologia , Anedonia/fisiologia , Aprendizagem da Esquiva/fisiologia , Núcleo Dorsal da Rafe/fisiologia , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , Animais , Depressão/fisiopatologia , Núcleo Dorsal da Rafe/metabolismo , Potenciais Evocados/fisiologia , Habenula/fisiologia , Hipocampo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Optogenética , Ritmo Teta , Proteína Vesicular 2 de Transporte de Glutamato/genética
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