Biology subjects

Beurrier, C.

Publications and source records attributed to Beurrier, C..

2 recordsLinked to original sources

bioRxiv2021

Inhibition of cholinergic interneurons potentiates corticostriatal transmission in D1 receptor-expressing medium-sized spiny neurons and restores motor learning in parkinsonian condition

Striatal cholinergic interneurons (CINs) respond to salient or reward prediction-related stimuli after conditioning with brief pauses in their activity, implicating them in learning and action selection. This pause is lost in animal models of Parkinsons disease. How this signal regulates the functioning of the striatum remains an open question. To address this issue, we examined the impact of CIN firing inhibition on glutamatergic transmission between the cortex and the medium-sized spiny projection neurons expressing dopamine D1 receptors (D1 MSNs). Brief interruption of CIN activity had no effect in control condition whereas it increased glutamatergic responses in D1 MSNs after nigrostriatal dopamine denervation. This potentiation was dependent upon M4 muscarinic receptor and protein kinase A. Decreasing CIN firing by opto/chemogenetic strategies in vivo rescued long-term potentiation in some MSNs and alleviated motor learning deficits in parkinsonian mice. Taken together, our findings demonstrate that the control exerted by CINs on corticostriatal transmission and striatal-dependent motor-skill learning depends on the integrity of dopaminergic inputs.

neuroscience↗

bioRxiv2018

Morphofunctional deficits in the cerebral cortex of NeuroD2 mutant mice are associated with autism/schizophrenia-like behaviors

We identified seven families associating NEUROD2 pathogenic mutations with ASD and intellectual disability. To get insight into the pathophysiological mechanisms, we analyzed cortical development in Neurod2 KO mice. Cortical projection neurons (CPNs) over-migrated during embryogenesis, inducing abnormal thickness and laminar positioning of cortical layers. At juvenile ages, dendritic spine turnover and intrinsic excitability were increased in L5 CPNs. Differentially expressed genes in Neurod2 KO mice were enriched for voltage-gated ion channels, and the human orthologs of these genes were strongly associated with ASD. Furthermore, adult Neurod2 KO mice exhibited core ASD-like behavioral abnormalities. Finally, by generating Neurod2 conditional mutant mice we demonstrate that forebrain excitatory neuron-specific Neurod2 deletion recapitulates cellular and behavioral ASD phenotypes found in full KO mice. Our findings demonstrate crucial roles for Neurod2 in cortical development and function, whose alterations likely account for ASD and related symptoms in the newly defined NEUROD2 mutation syndrome.

neuroscience↗