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Paul G. Mermelstein, Ph.D. Associate Professor, Department of Neuroscience E-mail: pmerm@umn.edu Mermelstein Lab (from L to R): Jason Weick, Sidney Kuo, Rachel Groth, Katherine Bradley, Marissa Iden, Paul Mermelstein

Research Interests:

Calcium Signaling and Cellular Excitability.

Mammalian neurons face the daunting task of integrating signals from tens of thousands of synaptic contacts. Based upon the temporal and spatial cues by which neurotransmitters are released, as well as inputs from more systemic signals (e.g. hormones) cells decide whether to become quiescent, fire one or a series of action potentials and/or alter their responses to future stimuli. But for long term changes in synaptic plasticity to occur, new proteins must be generated.

My lab focuses on elucidating (1) the mechanisms by which neurons decipher synaptic cues that are meant to activate protein synthesis (2) the second messenger systems that relay signals from the synapse to the nucleus leading to activity-dependent gene expression and (3) the functional consequences of expressing these transcripts into protein. Using a wide variety of powerful cellular and molecular techniques, we have found that repeated stimulation of excitatory synapses causes calcium to enter a cell through multiple ligand-voltage-gated ion channels. However, only calcium entering through a specific class of calcium channel (L-type) triggers the signal transduction pathways that lead to the activation of several different transcription factors and the synthesis of new protein.

Currently, we are focusing our attention on two separate transcription factors, CREB and NF-AT, both of which have been implicated in memory consolidation. Signaling to CREB and NF-AT rely heavily upon the calcium-binding protein calmodulin. However, while CREB-dependent gene expression is regulated by a series of calmodulin-dependent protein kinases, NF-AT activation is through the calmodulin-dependent protein phosphatase calcineurin. Future research will examine how L-type calcium channels differentially regulate these transcription factors, the mechanism by which L-type channels are 'privileged' in their ability to signal changes in the nucleus, and the alterations in cellular excitability that occur following CREB- and NF-AT-dependent gene expression. To do so, the lab will employ electrophysiological, fluorescent imaging, gene manipulation and transfection as well as DNA microarray techniques.Research examining this form of neuroplasticity will undoubtedly help neuroscientists better understand a variety of experimental themes such as learning and memory, neuronal development and drug addiction.

Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

Boulware MI, Kordasiewicz H, Mermelstein PG. Caveolin proteins are essential for distinct effects of membrane estrogen receptors in neurons. J Neurosci. 2007 Sep 12;27(37):9941-50.

Dewing P, Boulware MI, Sinchak K, Christensen A, Mermelstein PG, Micevych P. Membrane estrogen receptor-alpha interactions with metabotropic glutamate receptor 1a modulate female sexual receptivity in rats. J Neurosci. 2007 Aug 29;27(35):9294-300.

Groth RD, Coicou LG, Mermelstein PG, Seybold VS. Neurotrophin activation of NFAT-dependent transcription contributes to the regulation of pro-nociceptive genes. J Neurochem. 2007 Aug;102(4):1162-74.

Seybold VS, Coicou LG, Groth RD, Mermelstein PG. Substance P initiates NFAT-dependent gene expression in spinal neurons. J Neurochem. 2006 Apr;97(2):397-407.

Boulware MI, Mermelstein PG. The influence of estradiol on nervous system function. Drug News Perspect. 2005 Dec;18(10):631-7.

Bradley KC, Groth RD, Mermelstein PG. Immunolocalization of NFATc4 in the adult mouse brain. J Neurosci Res. 2005 Dec 15;82(6):762-70.

Boulware MI, Weick JP, Becklund BR, Kuo SP, Groth RD, Mermelstein PG. Estradiol activates group I and II metabotropic glutamate receptor signaling, leading to opposing influences on cAMP response element-binding protein. J Neurosci. 2005 May 18;25(20):5066-78.

Bradley KC, Boulware MB, Jiang H, Doerge RW, Meisel RL, Mermelstein PG. Changes in gene expression within the nucleus accumbens and striatum following sexual experience. Genes Brain Behav. 2005 Feb;4(1):31-44.

Groth RD, Dunbar RL, Mermelstein PG. Calcineurin regulation of neuronal plasticity. Biochem Biophys Res Commun. 2003 Nov 28;311(4):1159-71.

Groth RD, Mermelstein PG. Brain-derived neurotrophic factor activation of NFAT (nuclear factor of activated T-cells)-dependent transcription: a role for the transcription factor NFATc4 in neurotrophin-mediated gene expression. J Neurosci. 2003 Sep 3;23(22):8125-34.

Deisseroth K, Mermelstein PG, Xia H, Tsien RW. Signaling from synapse to nucleus: the logic behind the mechanisms. Curr Opin Neurobiol. 2003 Jun;13(3):354-65.

Weick JP, Groth RD, Isaksen AL, Mermelstein PG. Interactions with PDZ proteins are required for L-type calcium channels to activate cAMP response element-binding protein-dependent gene expression. J Neurosci. 2003 Apr 15;23(8):3446-56.

Seybold VS, McCarson KE, Mermelstein PG, Groth RD, Abrahams LG. Calcitonin gene-related peptide regulates expression of neurokinin1 receptors by rat spinal neurons. J Neurosci. 2003 Mar 1;23(5):1816-24.

Current Graduate Students:

Jessie Luoma (Neuroscience, University of Minnesota).

Christopher Stern (Neuroscience, University of Minnesota).

Former Graduate Students:

Rachel Groth (Ph.D. 2007, Neuroscience, University of Minnesota).

Marissa Iden Boulware (Ph.D. 2006, Neuroscience, University of Minnesota).

Jason Weick (Ph.D. 2005, Neuroscience, University of Minnesota).