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Salin, P.

Publications and source records attributed to Salin, P..

2 recordsLinked to original sources

Experimental and computational analysis of REM sleep distributed cortical activity in mice

Although classically Rapid-Eye Movement (REM) sleep is thought to generate desynchronized activity similar to wakefulness, it was found that some brain regions can express Slow Wave activity (SWA), a pattern which is normally typical of slow-wave sleep. To investigate possible underlying mechanisms, we analyze experimental recordings and introduce a computational model of mice cerebral cortex in REM sleep. We characterized the patterns of slow-wave activity across somatosensory and motor areas, and find that the most prominent REM-related SWA is present in the primary (S1) and secondary (S2) somatosensory areas, more rarely seen in motor cortex, and absent from prefrontal cortex or hippocampus. The SWA also tends to be synchronized in S1 and S2. We next investigated possible mechanisms by using a computational model of the mouse brain consisting of adaptive Exponential (AdEx) mean-fields connected together according to the mouse connectome. To compare with experimental data, the local field potential is calculated in each mouse brain region. To reproduce the experiments, we had to assume a heterogeneous level of adaptation in different cortical regions during REM sleep. In these conditions, the model reproduces some of the experimental observations in the somato-motor areas and the other cortical areas. We then used the model to test how the presence of SWA affects cortical responsiveness. Indeed, we find that the areas expressing SWA have diminished evoked responses, which may participate to a diminished responsiveness during REM sleep.

neuroscience↗

Targeted Tshz3 deletion in corticostriatal circuit components segregates core autistic behaviors

We previously linked TSHZ3 haploinsufficiency to autism spectrum disorder (ASD) and showed that embryonic or postnatal Tshz3 deletion in mice results in behavioral traits relevant to the two core domains of ASD, namely social interaction deficits and repetitive behaviors. Here, we provide evidence that cortical projection neurons (CPNs) and striatal cholinergic interneurons (SCINs) are two main and complementary players in the TSHZ3-linked ASD syndrome. We show that in the cerebral cortex, TSHZ3 is expressed in CPNs and in a proportion of GABA interneurons, while not in cholinergic interneurons or glial cells. TSHZ3-expressing cells, which are predominantly SCINs in the striatum, represent a low proportion of neurons in the ascending cholinergic projection system. We then characterized two new conditional knockout (cKO) models generated by crossing Tshz3flox/flox with Emx1-Cre (Emx1-cKO) or Chat-Cre (Chat-cKO) mice to decipher the respective role of CPNs and SCINs. Emx1-cKO mice show altered excitatory synaptic transmission onto CPNs and plasticity at corticostriatal synapses, with neither cortical neuron loss nor impaired layer distribution. These animals present social interaction deficits but no repetitive patterns of behavior. Chat-cKO mice exhibit no loss of SCINs but changes in the electrophysiological properties of these interneurons, associated with repetitive patterns of behavior without social interaction deficits. Therefore, dysfunction in either CPNs or SCINs segregates with a distinct ASD behavioral trait. These findings provide novel insights onto the implication of the corticostriatal circuitry in ASD by revealing an unexpected neuronal dichotomy in the biological background of the two core behavioral domains of this disorder.

neuroscience↗