Experience-Dependent Inhibitory Plasticity Is Mediated by CCK+ Basket Cells in the Developing Dentate Gyrus.
J Neurosci
; 41(21): 4607-4619, 2021 05 26.
Article
em En
| MEDLINE
| ID: mdl-33906898
Early postnatal experience shapes both inhibitory and excitatory networks in the hippocampus. However, the underlying circuit plasticity is unclear. Using an enriched environment (EE) paradigm during the preweaning period in mice of either sex, we assessed the circuit plasticity of inhibitory cell types in the hippocampus. We found that cholecystokinin (CCK)-expressing basket cells strongly increased somatic inhibition on the excitatory granular cells (GCs) following EE, whereas another pivotal inhibitory cell type, parvalbumin (PV)-expressing cells, did not show changes. Using electrophysiological analysis and the use of cannabinoid receptor 1 (CB1R) agonist WIN 55 212-2, we demonstrate that the change in somatic inhibition from CCK+ neurons increases CB1R-mediated inhibition in the circuit. By inhibiting activity of the entorhinal cortex (EC) using a chemogenetic approach, we further demonstrate that the activity of the projections from the EC mediates the developmental assembly of CCK+ basket cell network. Altogether, our study places the experience-dependent remodeling of CCK+ basket cell innervation as a central process to adjust inhibition in the dentate gyrus and shows that cortical inputs to the hippocampus play an instructional role in controlling the refinement of the synaptic connections during the preweaning period.SIGNIFICANCE STATEMENT Brain plasticity is triggered by experience during postnatal brain development and shapes the maturing neural circuits. In humans, altered experience-dependent plasticity can have long-lasting detrimental effects on circuit function and lead to psychiatric disorders. Yet, the cellular mechanisms governing how early experience fine-tunes the maturing synaptic network is not fully understood. Here, taking advantage of an enrichment-housing paradigm, we unravel a new plasticity mechanism involved in the maintenance of the inhibitory to excitatory balance in the hippocampus. Our findings demonstrate that cortical activity instructs the assembly of the CCK+ basket cell network. Considering the importance of this specific cell type for learning and memory, experience-dependent remodeling of CCK+ cells may be a critical determinant for establishing appropriate neural networks.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colecistocinina
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Giro Denteado
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Neurogênese
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Plasticidade Neuronal
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2021
Tipo de documento:
Article