InProSMod · Cholinergic and NMDAR-dependent recruitment of Layer 1 Interneuron shapes cortical motor Processing through network States Modulation
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-09-01 → 2024-02-28
- EU contribution
- €196,708
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Cholinergic and NMDAR-dependent recruitment of Layer 1 Interneuron shapes cortical motor Processing through network States Modulation
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.
Data: CORDIS, © European Union
Project objective
In the sensory cortex of awake mice, spontaneous activity has been shown to exhibit various regimes, characterized by various levels of spiking activity. Such diverse activity regimes, termed network states, have a profound impact on the computational properties during sensory processing. In the mouse barrel cortex, a major top-down pathway modulating sensory input is represented by the integration of inputs from the motor cortex and associative thalamus onto layer 1 (L1). Here I will characterize the synaptic and circuit properties underlying top-down control of sensory network states during whisking in L1. Using a combination of synaptic biophysics, in vivo electrophysiology, 2-photon imaging and theoretical modeling, I will define the important role of L1 interneurons in decoding top-down processing of sensory information. This research will generate valuable information to advance our knowledge of cortical circuit dynamics during normal cortical operations, with crucial implications for several brain disorders.
Original text from CORDIS.
Participants
- INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union