Methodologies

Behavioural: To assess the contribution of different brain regions to a certain form of behaviour, our approach typically entails inducing reversible inactivations of different interconnected brain nuclei via local administration of agents that temporarily suppress neural activity (local anesthetics, GABA agonists). Understanding how different brain regions in a particular neural circuit may interact can be extrapolated using disconnection, assymetrical inactivation designs.  Complementary psychopharmacological studies use either systemic or local administration of drugs that either block or mimic the effects of certain neurotransmitters, such as dopamine or glutamate.

Neurophysiological: Acute in vivo preparations in anesthetized animals use extracellular recordings of action potentials from single neurons.  In these studies we look at how neural activity in particular brain pathways can be altered by chemical or electrical stimulation of different inputs or neurotransmitter receptors.  By looking at the same pathways that we study behaviourally, we can obtain insight to the cellular mechanisms that underlie changes in behaviour induced by certain drugs. We also have the capability to record neural activity from multiple neurons in rats that have chronically-implanted electrodes.  These preparations allow us to correlate different patterns of neural firing associated with performance of behavioural tasks.

Specific Research Streams

Cortico-Thalamic-Striatal Circuitry and Behavioral Flexibility: The ability to alter behaviour in response to changes in the environment is an essential survival skill that is often impaired in a number of neuropsychiatric disorders.  In rodents, this ability can be tested with tasks that require animals to change the way they discriminate between different stimuli that may be associated with reward. This line of research uses both behavioural methodologies and neurophysiological recordings in awake, behaving animals to clarify how different input and output regions of the prefrontal cortex enable animals to behave in a flexible manner.  Recent work has begun to focus on how certain forms of synaptic plasticity can facilitate different forms of behavioural flexibility. Examples of tasks used include set-shifting, reversal learning , and reinstatement paradigms using either mazes or operant chamber-base protocols.

(Funding sources: NSERC, NARSAD) 

Dopaminergic Regulation of Decision Making: These studies investigate the neural basis of different forms of cost/benefit decision making, when animals are given a choice between smaller, easily obtainable rewards, and larger rewards associated with a greater cost.  These costs can include making animals work harder or wait longer to receive larger rewards, or by adding some risk to choosing the larger rewards.  A key focus is on the contribution of dopamine transmission to these processes, using both systemic and local pharmacological manipulations in dopamine terminal regions, including the prefrontal cortex, ventral striatum and the amygdala. These studies are typically conducted in operant chambers where rats choose between two levers associated with different magnitudes of rewards.

(Funding sources: CIHR)

Neurophysiological Interactions between Amygdala, Prefrontal Cortex and the Dopamine System: The amygdala, the dopamine system and the prefrontal cortex share reciprocal connections and regulate a number of emotional, learning and decision making functions.  This line of research is designed to clarify the neurophysiological interactions between these three brain regions, exploring how activation of one node in this circuit can increase or decrease neural activity in other downstream structures.  Much of our focus has been on how dopamine can modify the cellular interactions between these brain regions, and how the amygdala and prefrontal cortex can in turn enhance activity of dopamine neurons.

(Funding sources: CIHR)

Alterations in Prefrontal Cortical Circuits and Executive Functions by Psychostimulants: Repeated administration of drugs of abuse such as amphetamine or ketamine causes certain neurochemical and behavioural alterations that resemble those observed in diseases, such as schizophrenia and stimulant addiction.  We use both behavioral and neurophysiological methodologies to investigate how these treatments can: 1) disrupt processes such as behavioural flexibility, working memory, reward-related learning and decision making (modeling the cognitive dysfunction observed in these diseases) and 2) perturb the neurophysiological interactions between different brain regions known to facilitate these processes in the normal brain, thereby elucidating the cellular mechanisms that may underlie disruptions in behaviour induced by these treatments.

(Funding sources: CIHR, NARSAD, Dainippon Sumitomo Pharma Co)