Incremental learning involves the deployment of learning sequences leading to modifications of behavior and efficient mastery of complex tasks. This is implemented with training through discrete learning phases, each characterized by a specific behavioral profile. How this is influenced by the activity of individual brain systems, is poorly understood. The striatum constitute an attractive system to investigate this notion and sequential involvement of cortico-striatal parallel loops has been demonstrated to be responsible for progressive refinement of the behavioral response in skill learning. This project will ask whether this model, postulating a sequential involvement of striatal subsystems, can also be transferred to spatial navigation.
State of art techniques involving viral injections and optogenetic, will allow tracking of learning-related changes in the striatal activity and determination of pre- and post-synaptic contributions to advance a more anatomically and physiologically constrained view of how cortex communicates with striatum to encode complex associative learning. The findings will drive refinement of theoretical models, and may be insightful for developing new theories on the biological mechanisms underlying learning and memory.
Compared to the large body of evidence sustaining the involvement of cortico-striatal circuits in S-R learning, the understanding of the contribution of the striatal complex to spatial learning is still at its early stages. Therefore, detailed comparative analysis of presynaptic and postsynaptic functional contribution of discrete projection seems timely to disambiguate the role of striatal complex in spatial learning and memory and help refine the circuit model of incremental learning.
This proposal will impact at different levels: 1. From a theoretical point of view the findings will drive refinement of current models, challenging the view of multiple segregated memory systems; 2. It will provide insight to understand the neural determinant of the cognitive deficits observed in patients with striatal dysfunctions but also suggest possible therapeutic avenue to treat these symptoms from a behavioral and pharmaceutical point of view. Indeed, enhancing normal learning with optimized learning protocols is a therapeutic strategy already exploited in clinical practice. Pin point the cellular determinants of such effect has the possibility to identify novel, unexpected molecules involved in incremental learning, that might become candidate therapeutic targets in the clinic.