(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 GABAA receptor subtypes, was the ideal collaborator for this investigation. Together, we have discovered that enhanced expression of α4βδ GABAA 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).
Merlin, L. R., and Wong, R. K. S. (1997). Role of group I metabotropic glutamate receptors in the patterning of epileptiform activities in vitro. J. Neurophysiol. 78, 539-544.
Merlin, L. R., Bergold, P. J., and Wong, R. K. S. (1998). Requirement of protein synthesis for group I mGluR-mediated induction of epileptiform discharges. J. Neurophysiol. 80, 989-993.
Merlin, L. R. (1999). Group I mGluR-mediated silent induction of long-lasting epileptiform discharges. J. Neurophysiol. 82, 1078-1081.
Galoyan, S. M., and Merlin, L. R. (2000). Long-lasting potentiation of epileptiform bursts by group I mGluRs is NMDA receptor independent. J. Neurophysiol. 83, 2463-2467.
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. (2009). The fragile X mental retardation protein: a valuable partner in the battle against epileptogenesis. Epilepsy Curr. 9, 116-118.
Fuortes, M. G., Rico, M. J., and Merlin, L. R. (2010). Distinctions between persistent and reversible group I mGluR-induced epileptiform burst prolongation. Epilepsia (in press)
- 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