Biology subjects

Badreddine, N.

Publications and source records attributed to Badreddine, N..

2 recordsLinked to original sources

bioRxiv2024

Early alterations of motor learning and corticostriatal network activity in a Huntington's disease mouse model

Huntingtons disease (HD) is a neurodegenerative disorder that presents motor, cognitive and psychiatric symptoms as it progresses. Prior to motor symptoms onset, alterations and dysfunctions in the corticostriatal projections have been described along with cognitive deficits, but the sequence of early defects of brain circuits is largely unknown. There is thus a crucial need to identify early alterations that precede symptoms and that could be used as potential early disease markers. Using an HD knock-In mouse model (HdhCAG140/+) that recapitulates the human genetic alterations and that show a late and progressive appearance of anatomical and behavior deficits, we identified early alterations in the motor learning abilities of young mice, long before any motor coordination defects. In parallel, ex vivo two-photon calcium recordings revealed that young HD mice have altered basal activity patterns in both dorsomedial and dorsolateral parts of the striatum. In addition, while wild-type mice display specific reorganization of the activity upon motor training, network alterations present in the basal state of non-trained mice are not affected by motor training of HD mice. Our results thus identify early behavioral deficits and network alterations that could serve as early markers of the disease.

neuroscience↗

bioRxiv2024

Somatostatin interneurons select dorsomedial striatal representations of the initial learning phase

The dorsomedial striatum (DMS) is an associative node involved in the adaptation of ongoing actions to the environmental context and in the initial formation of motor sequences. In early associative or motor learning phases, DMS activity shows a global decrease in neuron firing, eventually giving rise to a select group of active cells, whose number is correlated with animal performance. Unveiling how those representation emerge from DMS circuits is crucial for understanding plasticity mechanisms of early adjustments to learning a task. Here, we hypothesized that inhibitory microcircuits formed by local interneurons are responsible for the genesis of early DMS representation and associated task performance. Despite the low density of somatostatin (SOM)-positive cells, we observed that selective manipulation of SOM cells disrupted reorganization of DMS activity and modulated initial phases of learning in two behavioral contexts. This effect was cell-specific as manipulation of parvalbumin-positive interneurons had no significant effect. Finally, we identified the high plasticity of SOM innervation in the DMS as a key modulator of the SPN excitability and firing activity. Hence, SOM interneurons set the pace of early learning by actively controlling the remapping of DMS network activity.

neuroscience↗