18/05 – Maxime ASSOUS : Integration of extrinsic inputs by selective striatal microcircuits

SPPIN’s webinar winter-spring 2021, UNUSUAL TIME – 18 May at 14h00, online – Ask link to a SPPIN member.

Maxime ASSOUS, Center for Molecular and Behavioral Neuroscience, Rutgers University, New Jersey

Integration of extrinsic inputs by selective striatal microcircuits

The striatum is the main input structure of the basal ganglia (BG), a system that is crucial not only for voluntary motor control, but also for reinforcement-mediated learning and higher cognitive functions. It is composed of GABAergic spiny projection neurons (SPNs, ~ 95% of striatal neurons), cholinergic interneurons (CINs, ~1%) and a large diversity of GABAergic interneurons (~4%). Perhaps the most important recent development in this field is the realization that the traditional network models of the striatum are no longer tenable. There are 3 main discoveries concerning striatal interneurons that compel revision of the understanding of the striatal circuitry: the large diversity of newly discovered interneuron types, their selective extrinsic innervation and complex intrinsic connectivity, as well as novel signaling mechanisms in particular for CINs via nicotinic receptors.

My previous and current research focuses on establishing new organizational principles regarding the integration of specific extrinsic inputs to the striatum by selective striatal microcircuits. After a brief overview of previously published results regarding the striatal integration of extrinsic glutamatergic innervation from various sources, I will mostly focus on ongoing research projects.

The first one concerns the organization of extrinsic GABAergic inputs to the striatum originating from the globus pallidus (GPe) and the thalamic reticular nucleus (TRN). Using anatomical tract-tracing, whole cell recordings and optogenetics I demonstrate that these inputs preferentially target striatal interneurons located in distinct striatal territories. Further, using an intersectional approach (Cre/Flp), I will show that subpopulation of GPe and TRN neurons innervate specific striatal neuronal populations demonstrating a high cell-type type selectivity in these afferents. Finally, I am currently developing in vivo calcium imaging using miniature endoscope (Inscopix®) and fiber photometry to examine the role of these projections in regulating striatal neurons activity in behaving animals.

I will also present preliminary data investigating the interconnection between striatal CINs and several populations of GABAergic interneurons mostly via nicotinic receptors. I demonstrate that CINs and GABAergic interneurons form an interconnected network independent from cortical and thalamic afferents. In these experiments, I also tested whether the selective removal of a nicotinic receptor subunit (β2, using β2^fl/fl mice), expressed postsynaptically specifically by some striatal GABAergic interneurons, has any influence in striatal related behaviors such as goal-directed actions or cognitive flexibility.