Lisa R. Merlin, MD

Basic mechanisms of epileptogenesis

Until now, treatment of epilepsy has been limited to the suppression of seizures.  However, the holy grail of the epilepsy research community has been to find a cure for epilepsy. Toward this end, the key questions that need to be answered are: (1) How does normal brain become epileptic? and (2) Is it possible for epileptic brain to "normalize?"  These have been the areas of my basic research endeavors.

(1) We have shown that transient activation of group I metabotropic glutamate receptors in the normal hippocampus elicits a persistent enhancement of excitability, producing a protein synthesis-dependent epileptic state. One can envision this mechanism being relevant to patients with head trauma or ischemic insults to the brain, in which massive glutamate release during the insult may induce excessive group I mGluR activation and result in the development of post-stroke or post-traumatic epilepsy.  By examining the necessary receptors, induction and maintenance mechanisms, and intracellular pathways involved, we hope to discover the means to prevent epileptogenesis and suppress resistant seizures in vulnerable patient populations (work done in collaboration with Bob Wong, Peter Bergold, Michaelangelo Fuortes, Marjorie Rico and others).

(2) Pediatric neurologists have long known that patients with certain subtypes of pediatric epilepsy outgrow their seizures in adolescence, suggesting there may be a way to enhance remission of epilepsy.  Dr. Smith, a colleague here at Downstate and an expert in the field of developmental changes in expression of GABA_A receptor subtypes, was the ideal collaborator for this investigation. Together, we have discovered that enhanced expression of α4βδ GABA_A receptors underlies the reduced seizure susceptibility of adolescent female mice (work done in collaboration with Sheryl Smith, Lie Yang, and Hui Shen).

Other research by us and colleagues pertains to medical curriculum development and educational reform (see publication list below).

Service Functions

• Member, American Academy of Neurology (AAN) Undergraduate Education Subcommittee (representative of the Association of University Professors of Neurology)
• Member, AAN Clerkship Director Innovation Award Selection Committee
• Member, NIH study section ZRG1 RPHB-R, Small Business: Psycho/Neuropathology, Lifespan Development, and STEM education
• Ad hoc reviewer of grants and manuscripts for various organizations and journals

• Merlin, L. R. (2002). Differential roles for mGluR1 and mGluR5 in the persistent prolongation of epileptiform bursts. J. Neurophysiol. 87, 621-625.
• Rico, M. J., and Merlin, L. R. (2004). Evidence that phospholipase D activation prevents group I mGluR-induced persistent prolongation of epileptiform bursts. J. Neurophysiol. 91, 2385-2388.
• Huszár, P., and Merlin, L. R. (2004). Contribution of GABAB receptor-mediated inhibition to the expression and termination of group I mGluR-induced ictaform bursts. Epilepsy Res. 61, 161-165.
• Cuellar, J. C., Griffith, E. L., and Merlin, L. R. (2005). Contrasting roles of protein kinase C in induction versus suppression of group I mGluR-mediated epileptogenesis in vitro. J. Neurophysiol. 94, 3643-3647.
• Merlin, L. R . (2008). "TOR"rents of excitement over rapamycin's antiepileptogenic potential. Epilepsy Curr. 8, 163-165.
• Fuortes, M. G., Faria, L. C., and Merlin, L. R. (2008). Impact of protein kinase C activation on epileptiform activity in the hippocampal slice. Epilepsy Res. 82, 38-45.
• Fuortes, M. G., Rico, M. J., and Merlin, L. R. (2010). Distinctions between persistent and reversible group I mGluR-induced epileptiform burst prolongation. Epilepsia 51, 1633-1637.
• Merlin, L. R., Horak, H. A., Milligan, T. A., Kraakevik, J. A., and Ali, I. I. (2014). A competency-based longitudinal core curriculum in medical neuroscience. Neurology 83, 456-462.
• Yang, L., Shen, H., Merlin, L. R., and Smith, S. S. (2016). Pubertal expression of α4βδ GABAA receptors reduces seizure-like discharges in CA1 hippocampus. Scientific Reports 6, 31928.
• Mehta, M. G., DeBacker, J., Weedon, J., Anziska, B. J., and Merlin, L. R. (2016). An analysis of incorporation of outpatient neurology patients in the neurology clerkship: impact on student performance. Neurology 86, S3.001.

List of Publications (Pub Med)