Research Abstract:
The broad aim of my research is to understand control of excitation and inhibition by neurotransmitters in the central nervous system. This is an important goal because neurotransmitter actions can be double-edged, underlying normal neurotransmission on the one hand and neurotoxicity on the other. In one project we are exploring the cellular and synaptic homeostatic response to physiological and pathophysiological depolarization. We find that the nervous system limits glutamate functioning but permits continued GABA functioning during and following excessive depolarization. These mechanisms likely help limit excitotoxicity during seizures or ischemia. Our findings have led us into studies of the factors controlling action potential initiation and fidelity in the hippocampus and into studies examining presynaptically silent synapses, synapses that fail to exocytose despite strong stimulation and despite the presence of available vesicles. Another major emphasis is a collaborative effort to understand the mechanisms by which endogenous neuroactive steroids directly modulate GABA and glutamate receptor function. For all of these studies we use electrophysiological, molecular, and imaging techniques applied to simple in vitro systems of neurons in culture and to intact brain slices, as well as to heterologous expression systems.
Selected Publications:
Kress GJ, Dowling MJ, Meeks JP, Mennerick S. High threshold, proximal initiation, and slow conduction velocity of action potentials in dentate granule neuron mossy fibers. J Neurophysiol 2008 100: 281-291.
Moulder KL, Jiang X, Chang C, Taylor AA, Benz AM, Conti AC, Muglia LJ, Mennerick S. A specific role for Ca2+ dependent adenylyl cyclases in recovery from adaptive presynaptic silencing. J Neurosci 2008 28 :5159-5168.
Cirrito JR, Kang JE, Lee J, Stewart FR, Verges DK, Silverio LM, Bu G, Mennerick S, Holtzman DM. Endocytosis is required for synaptic activity-dependent release of amyloid-beta in vivo. Neuron 2008 58: 42-51.
Eisenman LN, Shu HJ, Akk G, Wang C, Manion BD, Kress GJ, Evers AS, Steinbach JH, Covey DF, Zorumski CF, Mennerick S. Anticonvulsant and anesthetic effects of a fluorescent neurosteroid analog activated by visible light. Nat Neurosci 2007 10: 523-530.
Meeks JP, Mennerick S. Action potential initiation and propagation in CA3 pyramidal axons. J Neurophysiol 2007 97: 3460-3472.
Last Updated: 07/29/2008 |