Dataset Information

The Contribution of Premotor Cortico-Striatal Projections to the Execution of Serial Order Sequences.

ABSTRACT: Striatal activity is necessary to initiate and execute sequences of actions. The main excitatory input to the striatum comes from the cortex. While it is hypothesized that motor and premotor cortico-striatal projections are important to guide striatal activity during the execution of sequences of actions, technical limitations have made this challenging to address. Here, we implemented a task in mice that allows for the study of different moments to execute a serial order sequence consisting of two subsequences of actions. Using this task, we performed electrophysiological recordings in the premotor (M2) and primary motor (M1) cortices, and state-dependent optogenetic inhibitions of their cortico-striatal projections. We show that while both M2 and M1 contain activity modulations related to the execution of self-paced sequences, mainly, the premotor cortico-striatal projections contribute to the proper execution/structuring of these sequences.

SUBMITTER: Sanchez-Fuentes A

PROVIDER: S-EPMC8457420 | biostudies-literature | 2021 Sep-Oct

REPOSITORIES: biostudies-literature

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The Contribution of Premotor Cortico-Striatal Projections to the Execution of Serial Order Sequences.

Sánchez-Fuentes Asai A Ramírez-Armenta Kathia I KI Verma-Rodríguez Anil Kumar AK Díaz-Hernández Edgar E Aguilar-Palomares Antonio A Ramírez-Jarquín Josué O JO Tecuapetla Fatuel F

eNeuro 20210921 5

Striatal activity is necessary to initiate and execute sequences of actions. The main excitatory input to the striatum comes from the cortex. While it is hypothesized that motor and premotor cortico-striatal projections are important to guide striatal activity during the execution of sequences of actions, technical limitations have made this challenging to address. Here, we implemented a task in mice that allows for the study of different moments to execute a serial order sequence consisting of ...[more]

PMID: 34465613

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Project description:Background:Modafinil, a nonamphetaminic wake-promoting compound, is prescribed as first line therapy in narcolepsy, an invalidating disorder characterized by excessive daytime sleepiness and cataplexy. Although its mode of action remains incompletely known, recent studies indicated that modafinil modulates astroglial connexin-based gap junctional communication as administration of a low dose of flecainide, an astroglial connexin inhibitor, enhanced the wake-promoting and procognitive activity of modafinil in rodents and healthy volunteers. The aim of this study is to investigate changes in glucose cerebral metabolism in rodents, induced by the combination of modafinil+flecainide low dose (called THN102). Methods:The impact of THN102 on brain glucose metabolism was noninvasively investigated using 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography imaging in Sprague-Dawley male rats. Animals were injected with vehicle, flecainide, modafinil, or THN102 and further injected with 18F-2-fluoro-2-deoxy-D-glucose followed by 60-minute Positron Emission Tomography acquisition. 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography images were coregistered to a rat brain template and normalized from the total brain Positron Emission Tomography signal. Voxel-to-voxel analysis was performed using SPM8 software. Comparison of brain glucose metabolism between groups was then performed. Results:THN102 significantly increased regional brain glucose metabolism as it resulted in large clusters of 18F-2-fluoro-2-deoxy-D-glucose uptake localized in the cortex, striatum, and amygdala compared with control or drugs administered alone. These regions, highly involved in the regulation of sleep-wake cycle, emotions, and cognitive functions were hence quantitatively modulated by THN102. Conclusion:Data presented here provide the first evidence of a regional brain activation induced by THN102, currently being tested in a phase II clinical trial in narcoleptic patients.

Dataset Information

The Contribution of Premotor Cortico-Striatal Projections to the Execution of Serial Order Sequences.

Publications

The Contribution of Premotor Cortico-Striatal Projections to the Execution of Serial Order Sequences.

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