RESUMEN
Memories are believed to be encoded by sparse ensembles of neurons in the brain. However, it remains unclear whether there is functional heterogeneity within individual memory engrams, i.e., if separate neuronal subpopulations encode distinct aspects of the memory and drive memory expression differently. Here, we show that contextual fear memory engrams in the mouse dentate gyrus contain functionally distinct neuronal ensembles, genetically defined by the Fos- or Npas4-dependent transcriptional pathways. The Fos-dependent ensemble promotes memory generalization and receives enhanced excitatory synaptic inputs from the medial entorhinal cortex, which we find itself also mediates generalization. The Npas4-dependent ensemble promotes memory discrimination and receives enhanced inhibitory drive from local cholecystokinin-expressing interneurons, the activity of which is required for discrimination. Our study provides causal evidence for functional heterogeneity within the memory engram and reveals synaptic and circuit mechanisms used by each ensemble to regulate the memory discrimination-generalization balance.
Asunto(s)
Miedo/fisiología , Memoria/fisiología , Neuronas/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Encéfalo/fisiología , Giro Dentado/fisiología , Interneuronas/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/fisiología , Proteínas Proto-Oncogénicas c-fos/metabolismoRESUMEN
Taste palatability is centrally involved in consumption decisions-we ingest foods that taste good and reject those that don't. Gustatory cortex (GC) and basolateral amygdala (BLA) almost certainly work together to mediate palatability-driven behavior, but the precise nature of their interplay during taste decision-making is still unknown. To probe this issue, we discretely perturbed (with optogenetics) activity in rats' BLAâGC axons during taste deliveries. This perturbation strongly altered GC taste responses, but while the perturbation itself was tonic (2.5 s), the alterations were not-changes preferentially aligned with the onset times of previously-described taste response epochs, and reduced evidence of palatability-related activity in the 'late-epoch' of the responses without reducing the amount of taste identity information available in the 'middle epoch.' Finally, BLAâGC perturbations changed behavior-linked taste response dynamics themselves, distinctively diminishing the abruptness of ensemble transitions into the late epoch. These results suggest that BLA 'organizes' behavior-related GC taste dynamics.