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Brian N Mathur
 

Brian N Mathur Ph.D.

Academic Title: Assistant Professor
Primary Appointment: Pharmacology
bmathur@som.umaryland.edu
Location: BRB 4-011
Phone: 410-706-8239

Personal History:

I received my B.A (Neuroscience) from Oberlin College in 1998 where I performed honors research on comparative neuroanatomy with Mark Braford, Ph.D. Following college, I worked for four years at Lexicon Pharmaceuticals Inc., in The Woodlands, TX as a research associate doing molecular biology research. I received my Ph.D. (Neuroscience) in 2008 from Vanderbilt University under the mentorship of Ariel Y. Deutch, Ph.D. Following graduate school, I took a postdoctoral position at the National Institute of Alcohol Abuse and Alcoholism at the National Institutes of Health in Rockville, MD in the laboratory of David M. Lovinger, Ph.D before joining the faculty at the University of Maryland. I am a member of the Society for Neuroscience, Sigma Xi: The Scientific Research Society, Research Society on Alcoholism, and the International Basal Ganglia Society.

Research Interests:

Our research seeks to elucidate the molecular mechanisms underlying dysplastic changes that occur at central nervous system synapses in disorders of action, including Parkinson’s disease (paucity of action) and alcohol addiction (compulsive drinking). Towards this end, we are currently concentrating on two brain regions: the dorsal striatum and the anterior cingulate cortex/claustrum circuitry. Our overarching goal is to understand the circuit/synapse-specific changes that take place in these brain regions to give rise to action dysfunction and to devise circuit specific strategies for restoring synaptic function and normal behavior.

Current projects:

Ethanol remodeling of striatal inhibitory microcircuits

The dorsal striatum, a forebrain structure critical for habit formation, is disinhibited in animal models of chronic drinking.  We find that ethanol directly disinhibits the structure by depressing GABAergic synapses onto medium spiny neurons, the principal neurons of the striatum. We are determining the synaptic mechanisms underlying this observation and are currently testing methods of disrupting this phenomenon during voluntary drinking in mice.

Serotonin-mediated corticostriatal plasticity in L-DOPA-induced dyskinesia

The gold standard treatment for Parkinson’s disease is dopamine replacement therapy, commonly in the form of the dopamine precursor L-DOPA. L-DOPA is efficacious for 5-10 years until unwanted, involuntary, and debilitating movements known as dyskinesias develop.  Dyskinesia is thought to arise from dysfunction in striatal serotonergic and glutamatergic systems. We recently discovered that serotonin is capable of inducing a long-term depression of corticostriatal (glutamatergic) transmission.  Thus, we hypothesize that aberrant serotonin-mediated corticostriatal plasticity underlies L-DOPA-induced dyskinesia. We are testing this hypothesis using ex vivo brain slice electrophysiology and cyclic voltammetry.

Anterior cingulate cortex control of the claustrum

The anterior cingulate cortex and the claustrum have both been implicated in attention, a critical component of successful action learning.  The anterior cingulate projects most heavily to the claustrum, and vice versa.  However, the contribution of this circuit to attentional processes during action learning is completely unknown. This project seeks to describe this circuit and its contribution to action learning from synaptic to behavioral levels of analyses. 

Lab Techniques and Equipment:

The Mathur lab uses a variety of techniques to assess changes at identified synapse types and their contribution to behavior. Brain slice electrophysiology in combination with optogenetics is heavily employed to determine mechanisms of circuit-specific synaptic plasticity. Classical and modern neuroanatomical techniques are used to define circuits, including viral tract tracing and immunohistochemistry. Behavioral methods are currently being used to assess drinking behavior, motor function and learning. We also exploit in vivo optogenetic and chemogenetic methods to manipulate behavioral output. We use a variety of transgenic and conditional knockout mouse lines to achieve circuit-specific control and/or protein expression/deletion.

Laboratory Personnel:

  • Patrick Cody – Lab manager/technician/  
  • Mary Patton - Graduate Student
  • Brian Mathur - PI

We are actively seeking talented postdoctoral fellows. Please contact bmathur@som.umaryland.edu


Funding:

  • NIAAA K22 Career Transitional Award (2013 – 2016)
  • The Bachmann-Strauss Dystonia & Parkinson Foundation, Inc. (2014)

Patents:

Novel Human Proteins and Polynucleotides Encoding the Same (U.S. Patent Nos.)
7,074,591, 6,987,178, 6,919,192, 6,902,924, 6,902,923, 6,867,291, 6,849,443, 6,815,188, 6,476,210, 6,720,173, 6,610,537, 6,777,545, 6,593,125, 6,586,582, 6,579,710, 6,511,840, 6,403,784.

Genbank Entries:

BD263758, BD263758, DD084960 - DD084969, DD089518 - DD089524, DD052611 -DD-52615, DD051856, DD051857, DD041860, DD010732 - DD010734, AY017369, AY017368, AF427492.


Publications:

  1. Mathur BN, Tanahira C, Tamamaki N, Lovinger DM (2013) Voltage drives diverse endocannabinoid signals to mediate striatal microcircuit-specific plasticity. Nat Neurosci. Sep;16(9):1275-83.
  2. Klug JR, Mathur BN, Kash TL, Wang HD, Matthews RT, Robison AJ, Anderson ME, Deutch AY, Lovinger DM, Colbran RJ, Winder DG (2012) Genetic inhibition of CaMKII in dorsal striatal medium spiny neurons reduces functional excitatory synapses and enhances intrinsic excitability. PLoS One.7(9):e45323.
  3. Cachope R, Mateo Y, Mathur BN, Irving J, Wang HL, Morales M, Lovinger DM, Cheer JF (2012) Selective activation of cholinergic interneurons enhances accumbal phasic dopamine release: setting the tone for reward processing. Cell Reports. 2(1):33-41.
  4. Mathur BN, Lovinger DM (2012) Endocannabinoid-dopamine interactions in striatal synaptic plasticity. Front Pharmacol. 2012;3:66.
  5. Mathur BN, Lovinger DM (2012) Serotonergic action on dorsal striatal function. Parkinsonism Relat Disord. Parkinsonism Relat Disord. 18 Suppl 1:S129-31.
  6. Lovinger DM, Mathur BN (2012) Endocannabinoids in Striatal Plasticity. Parkinsonism Relat. Disord. Parkinsonism Relat Disord. 18 Suppl 1:S132-4.
  7. Cuzon Carlson VC, Mathur BN, Davis MI, Lovinger DM (2011) Subsets of Spiny Striosomal Striatal Neurons Revealed in the Gad1-GFP BAC Transgenic Mouse. Basal Ganglia. 1(4):201-21.
  8. Mathur BN, Capik NA, Alvarez VA, Lovinger DM. (2011) Serotonin induces long-term depression at corticostriatal synapses. J Neurosci. 31:7402-11.
  9. Mathur BN, Caprioli RM, Deutch AY. (2009) Proteomic analysis illuminates a novel structural definition of the claustrum and insula. Cereb Cortex. 219:2372-9.
  10. Torres-Altoro MI, Mathur BN, Drerup JM, Thomas R, Lovinger DM, O'Callaghan JP, Bibb JA. (2011) Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum. J Neurochem. 2011 Aug 16.
  11. Mathur BN, Deutch AY(2008) Rat meningeal and brain microvasculature pericytes co-express the vesicular glutamate transporters 2 and 3. Neurosci Lett. 435:90-4.
  12. Mathur BN, Neely MD, Dyllick-Brenzinger M, Tandon A, Deutch AY (2007) Systemic administration of a proteasome inhibitor does not cause nigrostriatal dopamine degeneration. Brain Res. 1168:83-9.
  13. Donoviel DB, Freed DD, Vogel H, Potter DG, Hawkins E, Barrish JP, Mathur BN, Turner CA, Geske R, Montgomery CA, Starbuck M, Brandt M, Gupta A, Ramirez-Solis R, Zambrowicz BP, Powell DR (2001) Proteinuria and perinatal lethality in mice lacking NEPH1, a novel protein with homology to NEPHRIN. Mol Cell Biol. 21:4829-36.
  14. Maor MH, Dubey P, Tucker SL, Shiu AS, Mathur BN, Sawaya R, Lang FF, Hassenbusch SJ (2000) Stereotactic radiosurgery for brain metastases: results and prognostic factors. Int J Cancer. 90:157-62.