Dr. Nicholas Graziane’s research looks to identify the molecular and cellular substrates that mediate a number of devastating brain diseases, including drug addiction and chronic pain. With the lab’s established animal models for these diseases, changes in synaptic transmission are examined, as are intrinsic membrane excitability of neurons and circuits that are thought to control motivation, reward and affective states using electrophysiology and optogenetic approaches.

The laboratory’s main project investigates the neurocircuits that control the long-term maintenance of opioid-context associations. Opioid-context associations occur during repeated opioid administration within a specific context (e.g., environmental surroundings), which leads to the transfer of the motivational and rewarding sensations of the drug to the environment in which they were taken. This in turn leads to drug-craving and contextual-drug relapse in drug-free states, which is a problem for abstinent opioid abusers. By identifying the neurocircuits that control and maintain opioid-context associations, the neurocircuit connections can potentially be reoriented using electrical brain stimulation protocols, thus permanently eliminating the associations. In order to get to this clinically relevant endpoint, rodent models of addiction are employed. Using conditioned place preference, which isolates context associations from other forms of associations like cue associations or operant associations, mice are conditioned to express opioid-context associations. Once the behavior is established, optogenetic techniques to isolate specific neurocircuit pathways are employed in order to uncover changes in glutamatergic transmission in the nucleus accumbens shell, a brain that regulates and controls opioid-induced context associations. This work includes a combination of innovative techniques, including behavior, in vivo and ex vivo optogenetic techniques, and ex vivo electrophysiological approaches in transgenic animals.