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Authors & Affiliations
Giulia Nato, Marco Fogli, Nicolas Marichal, Ilaria Ghia, Benedikt Berninger, Paolo Peretto, Annalisa Buffo, Luzzati Federico
Abstract
After excitotoxic lesions, subsets of striatal astrocytes undergo spontaneous neurogenic activation, leading to the local generation of a large number of neuroblasts for at least six months post-lesion. However, the functional integration of the lesion-induced neurons remains unclear. Fate mapping and 3D reconstruction analyses reveal that striatal neuroblasts undergo a maturation process in which they initially organize in clusters, subsequently disperse as individual cells, and gradually attain complex morphologies, often exhibiting dendritic spines. These neurons fail to express typical markers of striatal neurons and have a transient lifespan, similar to other models of physiological and pathological striatal neurogenesis. Surprisingly, rabies virus-based monosynaptic tracing indicates that despite their transient existence, striatal neuroblasts receive local inputs from striatal projection neurons and interneurons, as well as long-range connections from different cortical and thalamic areas. Electrophysiological recordings in acute brain slices showed that many of these local-generated cells acquired membrane properties similar to immature neurons, displaying transient inward currents and generating single action potentials in response to depolarizing current steps. Further, some individual neuroblasts received spontaneous excitatory synaptic inputs while others, likely consistent with a more mature status, generated action potentials repetitively and exhibited inhibitory postsynaptic currents. These results indicate that striatal neuroblasts functionally interact with pre-existing circuits, thus potentially taking part in post-lesion network plasticity supporting functional recovery after damage.