My project aims to understand how changes in cellular processes produced by specific signal transduction pathways influences long-term synaptic plasticity and mediates changes in behaviour. I’m primarily focused on the physiological and functional roles of specific receptors for drugs of abuse and their natural ligands. The in-vivo exposure to drugs of abuse and their behavioural effects are used as a model for investigating the role of long-term synaptic plasticity in the experience-dependent alterations in neuronal circuits, both under physiological and pathological conditions. The involvement of specific signal transduction pathways is assessed using transgenic animal models lacking intracellular molecular components or expressing cell-type-specific fluorescent proteins for visualization of distinct neuronal populations. Experiments are performed by an integrative approach combining behavioral analysis with neurophysiological techniques (electrophysiological and two-photon imaging recordings) using both an ex-vivo and in-vivo approach as well as with and in-vitro and in-vivo pharmacology.
Two main lines of research will be pursued:
The overall goal is to elucidate the synaptic mechanisms underlying the different phases of learning of goal-directed actions, their flexible use and how they become habitual. This is of particular interest given the proposed dysregulation of habitual control over behaviour in pathological conditions, including Parkinson’s disease and drug addiction. I’m mainly focused on the role of specific neuromodulatory pathways, such as the endocannabinoid-mediated signalling, in regulating neural circuits to produce experience-dependent behavioural changes. Endocannabinoids are important neuromodulators of both short-term and long-term synaptic plasticity in several brain areas where they play a role in a variety of processes, such as motor behaviour, cognition, learning and memory. To this purpose, mice are behaviourally trained to learn goal-direct actions (instrumental learning/habit formation) and the flexible use of actions (attentional set shifting task). This is followed by electrophysiological and imaging recordings to analyze changes in synaptic transmission and plasticity in brain areas relevant for motor control, drug habits and reward (e.g. dorsal striatum, NAc and prefrontal cortex).
Neurotransmitter and neuromodulatory receptors (e.g. dopamine-, endocannabinoid-, opioid- and cholinergic receptors) modulate a complex cascade of intracellular signals which play a critical role in behavioural and synaptic plasticity. Agonists and antagonists of these receptors are used in-vitro and in-vivo to directly evaluate their coordinated role on synaptic plasticity under physiological conditions in neuronal circuits relevant for learning process (hippocampus, dorsal striatum). Experiments are also performed in transgenic animals lacking specific signal transduction proteins, like components of the cAMP/PKA and ERK pathways or expressing cell-type-specific fluorescent proteins for visualization of distinct neuronal populations. Recent evidence highlights the development of forms of pathological synaptic plasticity in some psychiatric and neurological disorders. By means of the experimental approach mentioned above, I analyse the functional role of neuromodulator-dependent signalling in animal models of Alzheimer and Parkinson’s diseases. This will help to understand not only the neurophysiological mechanisms of some brain diseases but also to identify potential novel molecular targets in a therapeutic perspective.