Investigating the molecular basis of the shift from goal-directed to habitual behavior

According to current theories, actions are controlled by the balance between two dissociable processes acquired during learning. The flexible, goal-directed control of behavior, which is dependent on the causal relationship between the action and its outcome (A-O) and the automatic and inflexible habitual behavior that is insensitive to changes in A-O contingencies. The amount of training critically defines which cognitive process determines action control. Whilst at early stages behavior is goal-directed; with repeated practice behavior gradually becomes automatic and habitual. Lesion studies in rodents have identified two striatal sub-region that are at least partially responsible for the expression of goal directed and habitual behaviour, the dorso-medial (DMS) and dorso-lateral striatum (DLS) respectively. Within these structures striatal projection neurons integrate cortical glutamatergic signals and midbrain dopaminergic information through multiple post-synaptic receptors to shape synaptic plasticity and action output. Amongst which, the group I metabotropic glutamate receptors (mGluR1/5s) are ideally placed, integrating glutamatergic signals into cellular responses and regulating pre-synaptic glutamate release through endocannabinoids production. We found that in mice subjected to different training regimes of instrumental conditioning of nose poke for food reward, which promote either goal-directed (short-training) or habitual behavior (over-training), the inability of reverting A-O contingency after over-training was associated with a lack of activation of signalling cascades downstream mGluR1/5s. Preventing in-vivo the activation of mGluR5 during training, in the dorsolateral striatum (DLS), restored behavioral sensitivity to changes in A-O contingencies and averted biochemical changes. By using super resolution microscopy (STORM) and electrophysiology on ex-vivo brain slices, we also found that the capability of updating changes in A-O association is associated with a nanoscale reorganization of molecular components of the mGlur5-endocannabinoid (eCB) signalling and enhanced eCB-mediated LTD in goal-directed but not habitual mice.