The neostriatum: two entities, one structure?

The striosome (or patch) was first identified with anatomical techniques as neurons organized in a three-dimensional labyrinth inserted in and interdigitating the rest of neostriatum: the matrix. Striosome and matrix rapidly became known as two neuronal compartments expressing different biochemical markers, embryonic development and afferent and efferent connectivity. In spite of extensive intrinsic neuronal axonal and dendritic extensions supposed to exchange information between matrix and striosomes, evidence suggested the presence of independent areas. Here, we report that indeed these two areas do not exchange synaptic information. We used genetic expression of channel rhodopsin 2 carried by adeno-associated virus serotype 10 (AAVrh10) that only expresses in neurons of the matrix compartment. Whole-cell patch-clamp recordings of matrix neurons activated by light pulses consistently produced inhibitory postsynaptic currents (IPSCs), but the same manipulation did not evoke IPSCs in striosome neurons. The matrix contains both direct and indirect striatal output pathways. By targeting striatal matrix expression of designer receptors exclusively activated by a designer drug (DREADD) hM3di carried by AAVrh10, we were able to inhibit the matrix neuronal compartment of the dorsolateral striatum during performance of a learned single-pellet reach-to-grasp task. As expected, inhibition of matrix neurons by systemic administration of DREADD agonist clozapine-n-oxide interfered with performance of the learned task.