Biology subjects

Salin, P.

Publications and source records attributed to Salin, P..

4 recordsLinked to original sources

bioRxiv2024

Altered striosome-matrix distribution and activity of striatal cholinergic interneurons in a model of autism-linked repetitive behaviors

Repetitive behaviors are cardinal features of many brain disorders, including autism spectrum disorder (ASD). We previously associated dysfunction of striatal cholinergic interneurons (SCINs) with repetitive behaviors in a mouse model based on conditional deletion of the ASD-related gene Tshz3 in cholinergic neurons (Chat-cKO). Here, we provide evidence linking SCIN abnormalities to the unique organization of the striatum into striosome and matrix compartments, whose imbalances are implicated in several pathological conditions. Chat-cKO mice exhibit altered relationship between the embryonic birthdate of SCINs and their adult striosome-matrix distribution, leading to an increased proportion of striosomal SCINs. In addition, the ratio of striosomal SCINs with slow-irregular vs. sustained-regular firing is increased, which translates into decreased activity, further stressing the striosome-matrix imbalance. These findings provide novel insights onto the pathogenesis of ASD-related stereotyped behaviors by pointing to abnormal developmental compartmentalization and activity of SCINs as a substrate.

neuroscience↗

bioRxiv2023

Synaptic strength dynamics at cortical synaptic pathways is encoded by vigilance states duration

Interactions among brain areas are essential to most cognitive functions. Neuronal interactions between these areas depend on the modulation of synaptic strength. However, this modulation remains poorly understood. We recorded evoked synaptic responses at four hippocampal pathways in freely moving male rats across 24 hours: the Perforant Path to Dentate Gyrus (PP-DG), Fornix to Prefrontal Cortex (Fx-PFC), Fornix to Nucleus Accumbens (Fx-NAc), and the Schaffer Collaterals to CA1 (SC-CA1). We preserved the temporal dynamics of vigilance states and synaptic responses and show for the first time that synaptic strength at these four hippocampal pathways oscillates, with a very slow periodicity. We demonstrate that synaptic strength at the PP-DG, Fx-PFC, Fx-NAc pathways show a positive correlation with the duration of active wakefulness (aWK) and a negative one with the duration of most sleep states (slow wave sleep (SWS) and rapid eye movement sleep (REM)), with a positive peak correlation time-lag of 1 to 10 minutes for aWK and SWS at these 3 pathways. In contrast, no significant correlation peak is found at the SC-CA1 pathway. Finally, a model based on hypnogram data and synaptic strength at the PP-DG pathway was able to predict the evolution of synaptic strength at the PP-DG, Fx-PFC and Fx-NAc pathways, but not at the SC-CA1 pathway. These results reveal that the temporal succession of vigilance states, particularly aWK and SWS, may contribute to memory processes through rapid modulation of synaptic strength at several pathways during the sleep-wakefulness cycle, suggesting that memory processes are not only dependent on sleep amount but also on sleep architecture.

neuroscience↗

bioRxiv2023

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↗

bioRxiv2021

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↗