Meaghan Creed, PhD

DESCRIPTION OF RESEARCH:

My overarching scientific goal is threefold: 1) to understand how the excitability of genetically-defined neural circuits are modulated by opioids and dopamine, 2) to understand how these neural circuits shape reward processing in health and disease, 3) to leverage this understanding to develop novel neuromodulation therapies for disorders of reward processing. My immediate translational focus is on understanding how molecular and synaptic adaptations in the cortico-accumbal-pallidal network drive maladaptive behavior in models of chronic pain, mood and substance use disorders. Towards this goal, my multidisciplinary training began at the University of Toronto and Center for Addiction and Mental Health. Here, I dissected mechanisms underlying the therapeutic effects of deep brain stimulation (DBS) for movement disorders. Continuing this translational focus into my post-doc, I moved to the University of Geneva where I applied ex vivo and in vivo electrophysiology and optogenetic strategies to elucidate the nature of drug-evoked plasticity in the reward system. Notably, I developed a novel DBS protocol that abolished maladaptive behaviors in the context of addiction (See: Creed MC et al., Science 2015, Creed MC, Science 2017, Creed MC, Curr Opin Neurobiol, 2018).

In my own research program, I am building on this strong, multidisciplinary foundation to study how endogenous opioids and dopamine modulate synaptic plasticity and excitability of neurons within the cortico-striatal-pallidal network, and how altered function of this network contributes to behaviors such as impulsivity, anhedonia and reward seeking. Recently, we have identified two non-canonical populations of neurons in the ventral pallidum that potently regulate reward seeking behavior. A main goal of my program is to identify pharmacological targets that will modulate membrane excitability of these discrete neuronal populations, to alter their activity in vivo direclty or increase their susceptibility to plasticity induced by concomitant application of DBS. My integrated approach allows me to establish links of causality between membrane excitability of specific neural populations, activity of the circuits these neurons comprise, and behavior, with the ultimate goal of developing novel neuromodulation therapies for psychiatric disorders.

Since beginning my faculty position, I have established relationships with psychiatrists and neurologists to ensure the maximum clinical impact of this proposal. Moreover, I have trained a team of graduate students and technicians in all necessary behavioral, anatomical, optogenetic and electrophysiological techniques necessary to successfully carry out the proposed research (see: Tooley et al., Biol Psychiatry 2018, LeGates et al, Nature 2018, Chandra et al., Neuron 2017, Wulff et al., Brain Res, 2018).

Lab:  https://www.creedlab.org/people.html