Virginia M. Pickel, Ph.D
Professor of Neuroscience
Marijuana abuse by today’s teenagers is a major health concern because of the increased risk for emergence of cognitive and emotional dysfunctions that are traits among the RDoC-described symptoms of multiple psychiatric disorders that involve dysfunctions in the prefrontal cortex (PFC) and associated limbic brain regions. The mission of my laboratory is to establish the cellular signaling mechanisms underlying the deleterious long-term effects of marijuana on maturation of prefrontal cortical networks controlling cognitive functions which are often worsened by emotional stress such as social isolation during adolescence. This will be achieved using a multidisciplinary approach including molecular, structural, electrophysiological and behavioral measures in mouse models. These include chronic exposure of periadolescent mice to isolation stress and/or chronic administration of marijuana’s psychoactive compound, delta-9-tetrahydrocannabinol (THC) that acts mainly through cannabinoid-1 receptors (CB1Rs) in brain. This research will provide basic science information that is critical for design of improved therapeutic interventions for prevention and/or treatment of developmentally regulated frontal cortical dysfunctions. 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.
The major short term goals are to complete ongoing studies of the subcellular distribution of CB1Rs identifies sites within the PFC network where chronic adolescent administration of THC can suppress the postsynaptic assembly of functional NMDA receptors. This study involves the use of electron microscopic immunolabeling and patch clamp recording in the medial (m) PFC of adult male mice that received escalating doses (2.5-10 mg/kg/ip) of THC through peri-adolescence. We are also initiating new studies of the impact of social isolation on neural circuitry involved in the mediation of anxiety-like behaviors.
- 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.
- 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.
- 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.Gan JO, Bowline E, Lourenco FS and Pickel VM (2014).Adolescent social isolation enhances the plasmalemmal density of NMDA NR1 subunits in dendritic spines of principal neurons in the basolateral amygdala of adult mice. Neuroscience. 258:174-183, 2014.
- Garzon M, Pickel VM (2016) Electron microscopic localization of M2-muscarinic receptors in cholinergic and noncholinergic neurons of the laterodorsal tegmental and pedunculopontine nuclei of the rat mesopontine tegmentum. J Comp Neurol 524:3084-3103, 2016.
- Gasser PJ, Hurley MM, Chan J, Pickel VM (2017) Organic cation transporter 3 (OCT3) is localized to intracellular and surface membranes in select glial and neuronal cells within the basolateral amygdaloid complex of both rats and mice. Brain Structure and Function 222 (4):1913-1928.