Procedural memory and dynamics of striatal networks – ProMeSS

We all know the statement “It’s like riding a bike!” commonly used to convince someone that a task is really easy. However, the neural mechanisms making it so simple remains extremely complex. Indeed, once we learned how to ride a bike, or how to play the piano, we do it automatically, “without thinking” and we never forget. Furthermore, placing the fingers consciously on the piano keys makes things more difficult than playing “brainless”, leaving the fingers finding the right position. This form of memorization of our skills, called procedural memory, is a fundamental adaptive mechanism built upon daily experience to provide efficiency for common behaviors. It increases efficiency and set cognitive resources free for other tasks.
How does procedural memory build up? How is it encoded within the brain? How do neuronal circuits transform the activities of individual neurons into such complex sensorimotor sequences? Understanding how experience is converted to persistent modification within neuronal networks and how they become long-term memory engram is one of the greatest challenges in today’s integrative neuroscience.
The neural substrates underlying procedural memory involve the basal ganglia, and particularly their input stage, the striatum, key player for the integration and selection of functionally distinct cortical information, forming functional parallel loops (associative, sensory-motor…). Evidence suggests that during procedural learning, behavior evolves from being flexible and goal-directed to being habitual or automatic. Underlying neural control by striatal circuits is thought to shift from striatal circuits in dorsomedial striatum (DMS) to those in dorsolateral striatum (DLS). DMS is included in the associative loop that take into account the outcome contingencies of actions, while DLS is part of the sensory motor loop, which is less flexible and would underpin habit formation and repetitive behaviors. Therefore, at a macroscale level, the contribution of the cortico-basal ganglia functional loops to the different aspects of memory formation are well described. However, how the memory engram is precisely encoded within striatal networks and which are the engram cells of procedural memory remains to be determined.
Using a combination of cutting-edge technics, the goal of ProMeSS project is to better understand the neuronal dynamics underlying procedural memory and to identify dysfunctions in these networks associated with hyperkinetic disorders. The project is organized around three aims: (i) we will explore the organization and activity of the networks in DMS and DLS, to find the engram cells and to associate them with the different phases of procedural memory formation, (ii) we will identify and selectively manipulate specific cell types to their specific role in the engram, and (iii) we will use these fundamental bases to understand how memory and associated striatal dynamics are altered in hyperkinetic disorders, with the hope of identifying therapeutical targets.
Thanks to a cutting-edge multi-scale approach combining behavioral tests, multi-photon imaging, tracing studies, opto-/chemogenetics and electrophysiology, this project is likely to lead to important breakthroughs in the field. ProMeSS will indeed provide important insights in the neuronal bases of procedural memory engram and in the mechanisms of dysfunctions in hyperkinetics disorders.