Mark S Moehle

Mark S Moehle,

Assistant Professor

Business Phone: (352) 294-5571
Business Email:

Research Profile

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The overarching goal of the Moehle Laboratory is to understand the cellular, molecular, and circuitry changes that underlie both the motor and non-motor symptoms of movement disorders, and to leverage these discoveries into novel therapeutic strategies for these diseases. To this end, we have recently found that the M4 muscarinic acetylcholine receptor can directly oppose D1 dopamine receptor signaling/D1-SPN activity in the basal ganglia. Surprisingly, several lines of evidence shows this happens at the level of the substantia nigra pars reticulata and not the striatum. These novel findings have shown that hindbrain cholinergic sources of acetylcholine are as capable as striatal cholinergic interneurons in regulating basal ganglia output, and suggest that non-striatal basal ganglia structures can be directly modulated to alter the motor and non-motor symptoms of basal ganglia driven movement disorders. Importantly, these data also suggest that antagonism of the M4 receptor may be an efficacious treatment for movement disorders. The initial studies in my newly established independent laboratory will expand upon these ideas. Utilizing genetically, pharmacologically, and biochemically defined models of movement disorders (such as dystonia, Parkinson’s Disease, and Lewy Body Dementia) we will perform cutting edge pharmacological, electrophysiological, behavioral, biochemical, and in vivo fiber photometry techniques to interrogate the cellular, molecular, and circuitry level changes in the central nervous system in these model systems. These studies have the possibility to make substantial advances in our understanding of brain wide changes in diseases such as Parkinson’s Disease and dystonia, as well as provide the pre-clinical rationale to direct larger drug discovery efforts for unique targets in movement disorders.

Open Researcher and Contributor ID (ORCID)


Areas of Interest
  • Dystonia
  • Lewy Body Dementia
  • Movement Disorders
  • Muscarinic Acetylcholine Receptors
  • Parkinson’s disease


Activation of the mGlu1 metabotropic glutamate receptor has antipsychotic-like effects and is required for efficacy of M4 muscarinic receptor allosteric modulators.
Molecular psychiatry. 25(11):2786-2799 [DOI] 10.1038/s41380-018-0206-2. [PMID] 30116027.
Roles of the M4 acetylcholine receptor in the basal ganglia and the treatment of movement disorders.
Movement disorders : official journal of the Movement Disorder Society. 34(8):1089-1099 [DOI] 10.1002/mds.27740. [PMID] 31211471.
Cholinergic Projections to the Substantia Nigra Pars Reticulata Inhibit Dopamine Modulation of Basal Ganglia through the M4 Muscarinic Receptor.
Neuron. 96(6):1358-1372.e4 [DOI] 10.1016/j.neuron.2017.12.008. [PMID] 29268098.
Co-Activation of Metabotropic Glutamate Receptor 3 and Beta-Adrenergic Receptors Modulates Cyclic-AMP and Long-Term Potentiation, and Disrupts Memory Reconsolidation.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 42(13):2553-2566 [DOI] 10.1038/npp.2017.136. [PMID] 28664928.
α-Synuclein fibril-induced inclusion spread in rats and mice correlates with dopaminergic Neurodegeneration.
Neurobiology of disease. 105:84-98 [DOI] 10.1016/j.nbd.2017.05.014. [PMID] 28576704.
Urinary LRRK2 phosphorylation predicts parkinsonian phenotypes in G2019S LRRK2 carriers.
Neurology. 86(11):994-9 [DOI] 10.1212/WNL.0000000000002436. [PMID] 26865512.
Allosteric activation of M4 muscarinic receptors improve behavioral and physiological alterations in early symptomatic YAC128 mice.
Proceedings of the National Academy of Sciences of the United States of America. 112(45):14078-83 [DOI] 10.1073/pnas.1512812112. [PMID] 26508634.
Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration.
The Journal of biological chemistry. 290(32):19433-44 [DOI] 10.1074/jbc.M115.660001. [PMID] 26078453.
Leucine-rich repeat kinase 2 deficiency is protective in rhabdomyolysis-induced kidney injury.
Human molecular genetics. 24(14):4078-93 [DOI] 10.1093/hmg/ddv147. [PMID] 25904107.
M1 and M2 immune activation in Parkinson’s Disease: Foe and ally?
Neuroscience. 302:59-73 [DOI] 10.1016/j.neuroscience.2014.11.018. [PMID] 25463515.
The G2019S LRRK2 mutation increases myeloid cell chemotactic responses and enhances LRRK2 binding to actin-regulatory proteins.
Human molecular genetics. 24(15):4250-67 [DOI] 10.1093/hmg/ddv157. [PMID] 25926623.
Abrogation of α-synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats.
Proceedings of the National Academy of Sciences of the United States of America. 111(25):9289-94 [DOI] 10.1073/pnas.1403215111. [PMID] 24927544.
Differential LRRK2 expression in the cortex, striatum, and substantia nigra in transgenic and nontransgenic rodents.
The Journal of comparative neurology. 522(11):2465-80 [DOI] 10.1002/cne.23583. [PMID] 24633735.
Unique functional and structural properties of the LRRK2 protein ATP-binding pocket.
The Journal of biological chemistry. 289(47):32937-51 [DOI] 10.1074/jbc.M114.602318. [PMID] 25228699.
LRRK2 secretion in exosomes is regulated by 14-3-3.
Human molecular genetics. 22(24):4988-5000 [DOI] 10.1093/hmg/ddt346. [PMID] 23886663.
LRRK2 inhibition attenuates microglial inflammatory responses.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 32(5):1602-11 [DOI] 10.1523/JNEUROSCI.5601-11.2012. [PMID] 22302802.
Regional differences in expression of β-tubulin isoforms in schizophrenia.
Schizophrenia research. 135(1-3):181-6 [DOI] 10.1016/j.schres.2011.12.010. [PMID] 22264600.


Mar 2021 ACTIVE
M4 muscarinic acetylcholine receptor signaling as a potent regulator of motor deficits
Role: Principal Investigator
Jan 2021 ACTIVE
Impact of aggregated a-synuclein on altering neuronal physiology and plasticity in vivo and ex vivo in relevant animal models of LBD
Role: Principal Investigator
Funding: UF FOU
Jul 2015 ACTIVE
Research Pharmacology IX
Role: Project Manager
Funding: UF FOU


2015-2020 · Vanderbilt University
2010-2015 · University of Alabama at Birmingham
2006-2010 · Centenary College of Louisiana

Teaching Profile

Courses Taught
GMS7593 Topics in Pharmacology and Toxicology

Contact Details

(352) 294-5571