Plasticity of the corticostriatal projection: a question of certainty? – CorticoStriatal

Animals and humans navigate efficiently in their environment by taking advantage of salient sensory cues that they previously associated with specific actions. How animals take sensory-informed navigational decisions under variable levels of certainty is still poorly understood. Sensory inputs are transferred and integrated from periphery to cortex and down to the basal ganglia (BG), an ensemble of subcortical nuclei whose function has been linked to decision making and motor control. Striatum output is carried by two types of projection neurons (or medium spiny neurons, MSNs) forming the so-called direct and indirect BG pathways whose selective activation facilitates (dMSNs) or suppresses (iMSNs) movements. Because of this dichotomy, it was hypothesized that striatum contributed to action selection and execution. Recently, this model has been challenged on several grounds including the repeated observation that dMSNs and iMSNs are simultaneously active during behavior. One possible account is that the d/iMSN activities are primarily reflecting a covert determinant of behavior: the confidence, or certainty, that a given action will yield a positive outcome in a given context. Specifically, we will test in this proposal the hypothesis that the certainty with which an animal associates a particular sensory context with a specific action (or sensorimotor certainty) is determined by the relative connectivity strength between barrel cortex, a primary sensory cortical region, and the dMSNs and iMSNs.
To experimentally explore the validity of this hypothesis, we will divide our proposal in three tasks: Task_1- Establish the "baseline" functional connectivity pattern between barrel cortex and d/iMSNs in the sensorimotor region of striatum and examine its relation with spontaneous exploration biases. Task_2 : Manipulate sensorimotor certainty in a simple whisker-guided navigation task and examine the impact of this manipulation on d/iMSN sensory input strength and output spiking activity. Task_3 : Manipulate d/iMSN output activity and examine the impact of this manipulation on the animal confidence during navigation.
Our consortium is the result of a recent collaboration between Ingrid Bureau and David Robbe. We collaborate to pursue a common interest to understand the process of sensory control over goal-directed behaviors. This project benefits from our intimate knowledge of sensory integration in cortex and motor control in BG, and from our complementary technical expertise (electrophysiology in vivo and in brain slices, behavior and optogenetic manipulations).
The originality of the proposal stem from -1- its investigation of the topographic organization of barrel cortex-striatum functional connectivity and its functional relevance for behavior, when most studies focused on the outputs of MSN in the context of the production of movements. -2- its investigation to MSN sensory inputs and outputs in relation with a covert aspect of motor behavior, the uncertainty of selecting duly an action, when recent prominent works have focused their attention on how MSNs activity related to its overt aspects such as action selection or speed. -3- its investigation of MSN sensory inputs as a determinant for mouse behavioral lateralization -4- it challenges the classical hypothesis that movements need a local activation of dMSN combined with a broad inhibition iMSN in striatum.
Taking in account the numerous neurological diseases linked to BG (Parkinson disease, hyperactivity, obsessive-compulsive disease) and to its coupling with cortex (Huntington disease, hemi-neglect), gaining fundamental knowledge in the function of this brain region would have a broad impact on the neuroscience community and beyond.