Virginia M. Pickel, Ph.D
Professor of Neuroscience
Our Mission
The mission of my laboratory is to understand the in vivo neuroadaptations that foster the development of slow onset hypertension as well as adolescent onset of schizophrenia and the transition from recreational use to addiction of heroin and other abused drugs. This will be achieved using a multidisciplinary approach including electron microscopic immunolabeling, electrophysiology and behavioral measures in rodent models of sleep apnea, adolescent-isolation stress, and morphine or cocaine addiction. We will use these methods to test the hypothesis that region-specific trafficking of neurotransmitter (mainly glutamate and dopamine) and chemokine receptors is correlated with changes in cell firing and ongoing behavior. The brain regions under investigation include the, prefrontal cortex and striatum as well as the dopamine-enriched ventral midbrain and the paraventricular nucleus of the hypothalamus. Together, the results may have far reaching implications for understanding and devising new treatment strategies for treating the many neurological and psychiatric disorders whose symptoms are worsened by adaptive changes in the brain circuitry.
Lab Members
Michael Glass
Diane Lane
June Chan
Goals
The major short term goals are to complete ongoing and initiate new studies of the involvement of the immune system in neural adaptations that enable the development of slow pressor hypertension and addictive as well as other psychiatric diseases. This research is focused mainly on tumor-necrosis factor alpha (TNFα) and its receptors (TNFR1 and TNFR2) that are the respective mediators of pro-inflammatory and anti-inflammatory responses in both brain and peripheral tissues.
The long-term goals are to expand ongoing research to include studies of the influence of an adverse environment on the frontal cortical brain circuitry and maladaptive behaviors. We also hope to expand our research to include additional studies of the synergy between addictive and infectious diseases, particularly HIV.
Achievements
- Implemented electron microscopic dual immunolabeling as a tool for studying receptor trafficking.
- Identified mesocortical limbic targets of addictive drugs.
- Established brain sites and mechanisms underlying neurogenic hypertension.
- Implicated co-trafficking of dopamine D1 and NMDA receptors in rodent models of psychosis.
Recent Publications
- Fitzgerald ML, Lupica CR & Pickel VM. (2011) Decreased parvalbumin immunoreactivity in the cortex and striatum of mice lacking the CB1 receptor. Synapse. 65, 827-831, 2011
- Fitzgerald ML, Chan J, Mackie K, Lupica CR, Pickel VM. (2012) Altered dendritic distribution of dopamine D2 receptors and reduction in mitochondrial number in parvalbumin-containing interneurons in the medial prefrontal cortex of cannabinoid-1 (CB1) receptor knockout mice. J Comp Neurol 520:4013-4031.
- Lane DA, Chan J, Fitzgerald ML, Kearn CS, Mackie K, Pickel VM. (2012) Quinpirole elicits differential in vivo changes in the pre- and postsynaptic distributions of dopamine D(2) receptors in mouse striatum: relation to cannabinoid-1 (CB1) receptor targeting. Psychopharmacology 221:101-113.
- Pickel VM, Shobin ET, Lane DA, Mackie K (2012) Cannabinoid-1 receptors in the mouse ventral pallidum are targeted to axonal profiles expressing functionally opposed opioid peptides and contacting N-acylphosphatidylethanolamine-hydrolyzing phospholipase D terminals. Neuroscience 227C:10-21.
- Wang G, Coleman CG, Glass MJ, Zhou P, Yu Q, Park L, Anrather J, Pickel VM, Iadecola C (2012) Angiotensin II type 2 receptor-coupled nitric oxide production modulates free radical availability and voltage-gated Ca2+ currents in NTS neurons. Am J Physiol Regul Integr Comp Physiol 302:R1076-1083.
- Fitzgerald ML, Mackie K, Pickel VM (2013) Impact of social isolation during adolescence on the expression of dopamine D2 and cannabinoid CB1 receptors in the rat prefrontal cortex. Neuroscience, 235:40-50.
- Glass MJ, Robinson DC, Waters E, Pickel VM (2013_ Dopamine D1 receptor trafficking and morphology of subpopulations of spiny neurons in the nucleus accumbens are influenced by a local NMDA-NR1 deletion resulting in selective deficits in auditory startle and sociability. Synapse 67:265-279.
- Coleman CG, Wang G, Faraco G, Jackman K, Iadecola C, and Pickel VM (2013) Low dose systemic angiotensin II infusion elicits the production of reactive oxygen species and membrane trafficking of the NADPH oxidase p47phox subunit in the paraventricular nucleus of mouse hypothalamus J. Neurosci 33:4308-4316.
Joint Appointments
Adjunct Professor Rockefeller University
Collaborators
Costantino Iadecola
Diane Lane
Teresa Milner
Gang Wang
Joseph Anrather
Ping Zhou