Diane Lane, Ph.D.
Assistant Professor of Research in Neuroscience
My research investigates neuronal and non-neuronal mechanisms responsible for maladaptive changes in the function of various systems, including the dopaminergic reward/motor system and the descending pain modulatory system. My laboratory utilizes an in vivo systemic approach and combines microscopic immunolabeling (confocal, electron) with behavioral and extracellular electrophysiological analysis to examine functional effects of drug-induced changes in the reward and pain systems.
Illicit drug use, cravings, and relapse are attributed to progressive glutamate activation of dopamine neurons in the ventral tegmental area (VTA), however the mechanisms that initiate and maintain these changes are still unknown. Several research laboratories, including ours, have shown that various drugs of abuse increase synaptic expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) in ventral tegmental area (VTA) DA neurons, which in turn produces long-lasting activation of these neurons, a well-documented mechanism of addiction. However, progressive changes occur in other brain structures as addiction develops that cannot be solely attributed to glutamatergic plasticity of VTA DA neurons and the mechanisms that initial and maintain the changes in glutamate are still unclear.
We propose that the surge of VTA DA activity produced by initial drug use, triggers the release of endosomal vesicles into the extracellular space, which can then target and affect the function of cells throughout the nervous system. Extracellular vesicle-mediated cellular communication provides an ideal mechanism for the regional differences in function witnessed as addiction develops because extracellular vesicles contain numerous biologically active proteins and are released by most cells. In addition, extracellular vesicles can be transferred to different cell types, allowing for a greater range of cellular communication including neuronal-glial interactions. Our current studies include examining how different drugs of abuse alter extracellular vesicle content and targeting in the CNS and how these changes modulate neuronal activity and drug preference.
Pain serves an important function for our continual survival. However, when pain persists long after injury or with no discernable cause, it becomes problematic and can interfere with daily activities and productivity. Increased activity of a subset of neurons in the rostral ventromedial medulla (RVM) are associated with increased pain and hyperalgesia. My laboratory is interested in examining the contribution of inflammatory cytokines on the protracted glutamatergic activation of these RVM neurons as a mechanism of chronic pain. Current studies include examining the factors that trigger and the cellular signaling mechanisms responsible for continuous RVM “on-cell” activity in hopes of finding novel therapeutic targets to treat chronic pain.
Achievements & Publications
- Featured article, Journal of Neuroscience (vol 30 (50), Dec. 2013.
- Cover Illustration, Neuroscience (volume 169, issue 2), Aug. 2010.
- Recommendation by Faculty of 1000 Biology: evaluations for Lane DA et al J Neurosci 2008 Sep 24 28 (39) :9670-81 http://f1000biology.com/article/id/1123888/evaluation, Oct. 2008.
- Faraco, G., Sugiyama, Y., Lane, D.A., Garcia-Bonilla, L., Chang, H., Santisteban, M.M., Racchumi, G., Murphy, M., Van Rooijen, N., Anrather, J., Iadecola, C. (2016). Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension. J Clin Invest, 126(12): 4674-89.
- Pickel, V.M., Shobin, E.T., Lane, D.A., Mackie, K., (2012). Cannabinoid-1 receptors in the mouse ventral palidum are targeted to axonal profiles expressing functionally opposed opioid peptides and contacting N-acylphosphatidylethanolamine-hydrolyzing phospholipase D terminals. Neuroscience, 227: 10-21.
- Lane, D.A., Chan, J., Fitzgerald, M.L., Kearn, C.S., Mackie, K., Pickel, V.M., (2011). Quinpirole-induced locomotor suppression and trafficking of dopamine D2 receptors: Relation to cannabinoid-1 (CB1) receptor distribution in mouse striatum. Psychopharmacology, 221(1):101-13.
- Lane, D.A., Reed, B., Kreek, M.J., and Pickel, V.M., (2011). Synaptic redistribution of GluR1-containing AMPA receptors in dopamine neurons within the ventral tegmental area is dependent on the absence of cocaine following repeated administration: An effect opposite to that occurring in non-dopamine neurons. Neuropharmacology – special issue: Synaptic Plasticity and Addiction, 61(7): 1129-1140.
- Lane, D.A., Jaferi, A., Kreek, M.J., and Pickel, V.M., (2010). Acute and chronic cocaine differentially alter the subcellular distribution of AMPA GluR1 subunits in region-specific neurons within the mouse ventral tegmental area. Neuroscience, 169(2): 559-53.
- Lane, D.A., Chan, J., Lupica, C.R., and Pickel, V.M., (2010). Cannabinoid-1 (CB1) receptor expression is a determinant of the dendritic and axonal availability of mu-opioid receptors and dopamine axons in the mouse nucleus accumbens. Synapse, 64(12): 886-897.
- Jaferi, A., Lane, D.A., Pickel, V.M., (2009). Subcellular plasticity of the corticotropin-releasing factor (CRF) receptor in dendrites of the mouse bed nucleus of the stria terminalis following chronic opiate exposure. Neuroscience, 163(1): 143-154.
- Lane, D.A., Lessard, A., Chan, J., Colago, E.E.O., Zhou, Y., Schlussman, S., Kreek, M.J., and Pickel, V.M. (2008), Regional changes in the distribution of AMPA receptor GluR1 subunits in the rat ventral tegmental area following a single or multiple injections of morphine. J Neurosci, 28(39): 9670-9681.
- Lane, D.A., Patel, P.A., and Morgan, M.M., (2005). Evidence for an intrinsic mechanism of antinociceptive tolerance with the ventrolateral periaqueductal gray of rats, Neuroscience, 135(1): 227-34.
- Lane, D.A., Tortorici, V., and Morgan, M.M. (2004). Behavioral and electrophysiological evidence for tolerance to continuous morphine administration into the ventrolateral periaqueductal gray, Neuroscience, 125(1): 63-69.