John F. Marshall
Professor, Neurobiology and Behavior
Joint Appointment, Pharmacology
|Recovery of function after brain injury; cellular factors contributing to neurodegeneration; organization of basal ganglia motor systems; computer-assisted quanlitative localization of transmitter receptors in central nervous system|
|Neurobiology & Behavior Home Page|
|Pharmacology Home Page|
1974-1975 Fellow, Foundations Fund for Research in Psychiatry
1980-1982 Fellow in Neuroscience, Alfred N. Sloan Foundation
2005 Elected Fellow, American Association for the Advancement of Science
Our research centers on the capacity for reorganization in the central nervous system. Animals that sustain sudden injury to particular brain pathways can exhibit remarkable improvement in sensory and motor functions. Although the models of strutural and chemical reorganization in the brain-damaged animals provided new insight into the remarkable diversity of neuronal mechanisms that permit restoration of function, human neurodegenerative disorders (especially those associated with aging-such as Parkinson's and Alzheimer's diseases) are insidious in onset. Two major forefronts of research are to identify the processes that dispose certain neurons to degenerate in these diseases, and to determine means by which the brain's compensatory mechanisms may be induced to retard slow degenerative processes or to counteract their function consequences.
These considerations have prompted an analysis of patterns of brain dopaminergic innervation of the basal ganglia and studies of the distribution of the major subtypes of dopamine receptor (D-1 and D-2) in this motor area. In particular, using quantitative autoradiographic markers for the dopamine nerve terminals as well as for the D-1 and D-2 receptors, a complete picture has emerged of the organization of dopaminergic synapses in this structure. Important new information has emerged from our research concerning how this synaptic neurochemistry reorganizes itself in rodent and nonhuman primate models of Parkinson's disease. Similar analyses have been performed on postmortem human basal ganglia tissue, and experiments are planned to extend these studies to postmortem tissue derived from patients with diagnosed Parkinsonism.
Our research also is actively investigating factors responsible for the neurodegeneration occurring in Parkinsonism by using animals that undergo injury to the nigrostriatal dopamine projection as a consequence of exposure to neurotoxic agents (6-hydroxydopamine, MPTP, methamphetamine) or as a mutation ("weaver" mouse). Just as in Parkinson's disease, rodents undergoing degeneration to this pathway show considerable heterogeneity in their pathology, with certain dopamine-containing neurons being more vulnerable than others to injury. Cellular markers that distinguish vulnerable from resistant neurons have been identified.
Selected publications related to current funding:
1) Weihmuller FB, O'Dell SJ, Cole BN, Marshall JF (1991) MK-801 attenuates the dopamine-releasing but not the behavioral effects of methamphetamine: an in vivo microdialysis study. Brain Res 549:230-235. PMID:1884217.
2) O'Dell SJ, Weihmuller FB, Marshall JF (1991) Multiple methamphetamine injections induce marked increases in extracellular striatal dopamine which correlate with subsequent neurotoxicity. Brain Res 564:256-260. PMID:1810626.
3) Eisch AJ, Gaffney M, Weihmuller FB, O'Dell SJ, Marshall JF (1992) Striatal subregions are differentially vulnerable to the neurotoxic effects of methamphetamine. Brain Res 598:321-326. PMID:1486494.
4) O'Dell SJ, Weihmuller FB, Marshall JF (1993) Methamphetamine-induced dopamine overflow and injury to striatal dopamine terminals: attenuation by dopamine D1 or D2 antagonists. J Neurochem 60:1792-1799. PMID:8473897.
5) Eisch AJ, O'Dell SJ, Marshall JF (1996) Striatal and cortical NMDA receptors are altered by a neurotoxic regimen of methamphetamine. Synapse 22:217-225. PMID:9132989.
6) Eisch AJ, Schmued LC, Marshall JF (1998) Characterizing cortical neuron injury with Fluoro-Jade labeling after a neurotoxic regimen of methamphetamine. Synapse 30:329-333. PMID:9776136.
7) O'Dell SJ, Marshall JF (2000) Repeated administration of methamphetamine damages cells in the somatosensory cortex: overlap with cytochrome oxidase-rich barrels. Synapse 37:32-37. PMID:10842349.
8) Schroder N, O'Dell SJ, Marshall JF (2003) Neurotoxic methamphetamine regimen severely impairs recognition memory in rats. Synapse 49:89-96. PMID:12740864.
9) Belcher AM, O'Dell SJ, Marshall JF (2006) A sensitizing regimen of methamphetamine causes impairments in a novelty preference task of object recognition. Behav Brain Res 170:167-172. PMID:16600393.
10) Marshall JF, Belcher AM, Feinstein EM, O'Dell SJ (2007) Methamphetamine-induced neural and cognitive changes in rodents. Addiction 102 Suppl 1:61-69. PMID:17493054.
11) Belcher AM, Feinstein EM, O'Dell SJ, Marshall JF (2008) Methamphetamine influences on recognition memory: comparison of escalating and single-day dosing regimens. Neuropsychopharmacology 33:1453-1463. PMID:17637607.
12) Gross NB, Marshall JF (2009) Striatal dopamine and glutamate receptors modulate methamphetamine-induced cortical Fos expression. Neuroscience 161:1114-1125. PMID:19374938. PMCID: PMC2716135.
13) Izquierdo A, Belcher AM, Scott L, Cazares VA, Chen J, O'Dell SJ, Malvaez M, Wu T, Marshall JF (2010) Reversal-specific learning impairments after a binge regimen of methamphetamine in rats: possible involvement of striatal dopamine. Neuropsychopharmacology 35:505-514. PMID:19794407. PMCID: PMC2795129.
14) O'Dell SJ, Feinberg LM, Marshall JF (2011) A neurotoxic regimen of methamphetamine impairs novelty recognition as measured by a social odor-based task. Behav Brain Res 216:396-401. PMID:20797410.
15) Gross NB, Duncker PC, Marshall JF (2011) Striatal dopamine D1 and D2 receptors: Widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity. Synapse. PMID:21584865.
|Grant||NIDA RO1 DA12204, Methamphetamine Abuse and Cortical Injury, John F. Marshall, PI|
2005 Molecular and Cellular Cognition Society
1999 International Basal Ganglia Society
1991 International Brain Research Organization
1991 New York Academy of Sciences
1989 Integrative/Behavioral Neuroscience Group
1978 Brain Neurochemicals and Behavior Society
1977 Society for Neuroscience
1973 American Association for the Advancement of Scie
1972 Society of Sigma Xi
1970 Phi Beta Kappa
Neurobiology and Behavior
|Research Center||Center for Neurobiology of Learning and Memory|
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=2141|