Justin Anair PhD
PhD Candidate
Parker Lab
Department of Neuroscience
Title: "A novel schizophrenia model of chronic dopamine dysregulation"
Abstract: "Dopamine dysfunction in the nigrostriatal pathway is a hallmark of schizophrenia, with patients experiencing psychosis showing elevated dopamine in the associative striatum. While transient activation of substantia nigra pars compacta (SNc) dopamine neurons is sufficient to disrupt cognition, social behavior, and locomotion, how chronic nigrostriatal hyperdopaminergia contributes to schizophrenia symptoms remains poorly understood. To address this, we virally introduce the bacterial voltage-gated sodium channel NaChBac into SNc dopamine neurons. NaChBac expression increases neuronal excitability, alters action potential waveform, and raises maximal firing rate without disrupting intrinsic pace-making. This enhanced excitability drives striatal dopamine accumulation and broadly alters striatal neurochemistry. Behaviorally, NaChBac mice show impaired perceptual discrimination, working memory deficits, reduced social interaction, and elevated baseline locomotion — a profile consistent with core schizophrenia symptom domains. Ongoing work is examining how these changes in dopamine tone change the activity of D1- and D2-expressing spiny projection neurons, with the goal of understanding how chronic nigrostriatal dysregulation drives circuit-level dysfunction underlying psychosis."
Jenna Ward
(815) 529-6182
Email