Anatomical and Functional Characterization of Neuronal Projections from the Basolateral Amygdala and Auditory Cortex to the tail of the striatum

novembre 2024

Directeur(s) de thèse : François Georges

Résumé de thèse

To understand the anatomo-functional organization of the “auditory striatum,” we investigated its capacity for multimodal integration. Specifically, we explored how this structure integrates inputs from the auditory cortex and the basolateral amygdala (BLA), a key limbic region crucial for encoding information relevant to fear-related behaviors and anxiety states. Given that the BLA-to-striatum (BLA—TS) pathway remains poorly characterized, our study aimed to elucidate the anatomo-functional organization of these two key pathways, with a focus on their interaction with the dopaminergic innervation of the TS.

We first sought to dissect the projections from the BLA and auditory cortex (AUV) to the TS using retrograde and anterograde tracing techniques. Our findings demonstrate that the TS receives inputs from the amygdala of both hemispheres, with a predominant contribution from the ipsilateral BLA. For the AUV, the majority of TS innervation also originates from the ipsilateral side. We further mapped the projection patterns of these pathways, showing that BLA neurons primarily target the dorsal and ventrolateral regions of the TS, areas enriched in tyrosine hydroxylase (TH). In contrast, AUV neurons mainly project to the ventral TS. Additionally, we observed that the BLA-TS pathway does not innervate PV interneurons, contrary to the AUV-TS pathway.

Regarding dopaminergic innervation, our results reveal multiple sources, with most inputs arising from the substantia nigra pars compacta (SNc) but also from the substantia nigra pars lateralis (SNL) and ventral tegmental area (VTA) in roughly equal proportions. This finding was confirmed through selective lesioning of dopaminergic neurons.

Finally, we assessed the functional connectivity of these pathways using fiber photometry and provided functional evidence of their connectivity through electrical stimulation. Robust responses in the TS were recorded following stimulation of both the BLA and AUV. Additionally, we compared the evoked responses between the ipsilateral and contralateral BLA inputs, as well as between the AUV and BLA pathways.

Overall, this study offers a detailed anatomical characterization of the AUV and BLA inputs to the TS, as well as the multiple origins of dopaminergic innervation. Functionally, it also allowed for a comparison of the glutamatergic inputs to the TS and their distinct roles in modulating striatal activity.