TRANSCRIPTIONAL SIGNATURES OF PYSCHOSTIMULANTS IN THE TAIL STRIATUM

Efficient sensory processing is essential for survival and multisensory integration helps prioritize actions in response to significant events. However, disruptions in sensory processing can lead to over- or under-responsiveness, often linked to impaired inhibition and goal-directed behavior. The caudal part of the striatum, or tail of the striatum (TS), defines a fourth striatal domain and acts as a crucial hub for sensory processing. Knowing the impact of stimulants on sensory processing, it is important to determine how these drugs regulate the activity of TS-Spiny Projections Neurons (SPNs) to understand their elusive functions. Recent evidence indicate that the TS displays a unique spatiomolecular organization defining distinct subdomains characterized by specific arrangement of D1- and D2-SPNs. Here, we evaluated the transcriptional regulation of several Immediate Early Genes (IEGs) induced by different doses of d-amphetamine in TS-SPNs under basal conditions and in conditional knockout (cKO) mice for the dopamine D2-autoreceptor, known to be hypersensitive to psychostimulants. Cell-specific mRNA analysis revealed that low doses of d-amphetamine elicit different regulations between induction of direct effector IEGs compared to transcription factors, depending on the TS-SPNs subtype. In addition, we showed an alteration in basal expression of transcription factors in D2-SPNs of the cKO mice. But, low doses of stimulant do not induce change in direct effector IEGs expression in neither D2-SPNs or D1-SPNs. Future experiments will determine how higher doses of d-amphetamine might hijack functional properties of D1- and D2-SPNs, in order to understand how the TS might participate in abnormal sensory processing induced by stimulants.