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Projection Specific Information Coding in Frontal Cortical Networks.

Irene Lenzi1, Alice Despatin2, Nilufar Nojavan Lahiji1, Moritz Nesseler2, Daniel Medvedev1, Luca Koenig2, Marc Spehr2, Björn Kampa2, Simon Musall1

1 Forschungszentrum Jülich
2 RWTH Aachen University

The anterior lateral motor cortex (ALM) is crucial for integrating sensory information to drive associated behaviour. This process relies on long-range projections to subcortical regions, especially the striatum, which receives projections from cortico-striatal neurons (CStr). A potential role for CStr neurons is to promote learning of new behaviors. However, the specific role of CStr neurons during learning remains unclear. Here, we retrogradely labeled CStr neurons in ALM and performed 2-photon imaging over a series of behavioral tasks with increasing cognitive demand. First, mice underwent an innate behavior. Second, they learned to associate the location of a sound to the side of a water reward, and lastly had to retain their choice during a delay period. Across sessions, we observed a clear increase in choice selectivity for all ALM neurons, suggesting a strengthening of choice-related circuitry. To causally confirm these results, we optogenetically inactivated either all excitatory or only CStr neurons in ALM. Inhibiting CStr neurons during the innate task only impaired performance before, but not after learning. To further isolate this effect, we used the synaptic silencer eOPN3 to inactivate ALM projections to either the striatum, the thalamus or the superior colliculus (SC). In agreement with our earlier results, we found that inhibiting CStr projections reduced task performance only early in training, whereas SC and thalamus became more relevant over time. Overall, our results demonstrate that task learning induces long-lasting changes in choice-related circuitry in ALM with distinct subcortical projection pathways performing different roles in the acquisition of new behaviors.