Synaptic plasticity in the perforant pathway drives inhibitory reorganization enhancing dentate gyrus functionality
In the dentate gyrus (DG), tight inhibitory control confines the activity of granule cells (GCs)-a key characteristic for its proposed role as a pattern separator. Nonetheless, a conundrum arises concerning the balance between sparseness of GC firing and the activity level needed for efficient trans...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2026 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/424916 |
| Acceso en línea: | http://hdl.handle.net/10261/424916 https://api.elsevier.com/content/abstract/scopus_id/105029914060 |
| Access Level: | acceso abierto |
| Palabra clave: | Neuroscience Behavioral neuroscience |
| Sumario: | In the dentate gyrus (DG), tight inhibitory control confines the activity of granule cells (GCs)-a key characteristic for its proposed role as a pattern separator. Nonetheless, a conundrum arises concerning the balance between sparseness of GC firing and the activity level needed for efficient transmission downstream to CA3. Using in vivo electrophysiology, pharmacogenetics, and computational modeling, we identified a synaptic plasticity mechanism that decouples excitation from inhibition, enhancing information encoding and transmission without compromising pattern separation. Long-term synaptic potentiation of the perforant pathway, in addition to strengthening the glutamatergic synapses into GCs, depressed feedforward perisomatic inhibition. Computational modeling revealed a functional reorganization of the DG inhibitory network that decorrelated excitation/inhibition, enhanced GC burst firing, and improved temporal and spatial discrimination within the entorhinal-cortex-DG-CA3 network. Consistently, targeting parvalbumin + interneurons to reduce perisomatic inhibition during memory encoding improved pattern separation in freely behaving mice. Overall, our findings uncover a plasticity mechanism that boosts DG output while preserving its pattern separation function. |
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