Cholinergic and NMDAR-dependent recruitment of Layer 1 Interneuron shapes cortical motor Processing through network States Modulation

Información del proyecto

InProSMod

Identificador del acuerdo de subvención: 892175

DOI

10.3030/892175

Proyecto cerrado

Fecha de la firma de la CE 12 Marzo 2020

Fecha de inicio 1 Septiembre 2021

Fecha de finalización 28 Febrero 2024

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 196 707,84

Aportación de la UE

€ 196 707,84

Coordinado por

INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE
France

Periodic Reporting for period 1 - InProSMod (Cholinergic and NMDAR-dependent recruitment of Layer 1 Interneuron shapes cortical motor Processing through network States Modulation)

Período documentado: 2021-09-01 hasta 2023-08-31

Resumen del contexto y de los objetivos generales del proyecto

Brain disorders are one of the greatest health challenges. It is estimated that around 30% of Europeans will suffer from a neurological and/or mental disorder at some point in their live. Given their immense socio-economic impact, it is therefore crucial to find new treatments for brain disorders.
However, cognition in the healthy brain relies on a tremendous complexity at the cellular and circuit levels. Part of this complexity resides in the presence of diverse interneuronal circuits that enable inhibitory interactions between brain modules. One such circuit is the inhibitory network found in the most superficial layer of the cortex (Layer 1, L1) that is strongly driven by contextual information from higher order brain modules (i.e. top-down signals).
In this project, I characterized the synaptic and circuit properties underlying the top-down control of cortical networks by L1 interneurons. My analysis revealed that the activity of L1 interneurons was strongly dependent on the N-methyl-D-aspartate receptor (NMDAR). Next, I found that normal sensorimotor function was dependent on L1 integration and was impaired upon deletion of the NMDAR in L1 interneurons. Those results therefore emphasized the important contribution of the cellular mechanisms (here the NDMAR) in L1 interneurons in shaping cortical processing in the healthy brain. Importantly, this study points to a new therapeutic target for NMDAR-related diseases such as schizophrenia or depression: L1 interneurons. By suggesting new therapeutic approaches for NMDAR-related disease, the fundamental knowledge generated in this action could therefore have crucial implications for brain disorders.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

In this project, I characterized the synaptic and circuit properties of L1 interneurons combining experimental characterization and theoretical analysis. I found that L1 interneurons had a very strong component mediated by the N-methyl-D-aspartate receptor (NMDAR) in synaptic transmission. Next, I found that normal sensorimotor function was dependent on L1 integration and was impaired upon deletion of the NMDAR in L1 interneurons.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

This action has substantially improved our knowledge on the role of interneurons in cortical processing. Notably, it emphasized the important contribution of the cellular mechanisms (here the NDMAR) in L1 interneurons in shaping cortical processing in the healthy brain. Most importantly, this study points to a new therapeutic target for NMDAR-related diseases such as schizophrenia or depression: L1 interneurons. The fundamental knowledge generated in this action could therefore have crucial implications for brain disorders and therefore strongly reduce their socio-economic impact.

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