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Faculty
 Eric
S. Levine
Associate Professor of Neuroscience
Director, Graduate Program in Neuroscience
eslevine@neuron.uchc.edu
Areas of Interest:
My laboratory studies synaptic physiology
in the hippocampus and neocortex. Our recent work has focused on the
functional roles of two novel classes of synaptic messengers, endogenous
cannabinoids and nerve growth factors.
Endogenous Cannabinoids: The activity of cortical pyramidal
cells, the sole output cells of the cortex, is tightly controlled by
distinct classes of GABAergic inhibitory interneurons. These
interneurons maintain high firing rates in vivo and provide
potent inhibition to pyramidal cells, thus regulation of this inhibitory
tone is essential for proper cortical function. Recent data from our
laboratory and others indicate that the cannabinoid system may play an
important role in modulating GABAergic inhibition. The type 1
cannabinoid (CB1) receptor, found in presynaptic terminals of GABAergic
neurons, is one of the most highly expressed G-protein coupled receptors
in the forebrain, and mediates the well-known effects of exogenous
cannabinoids on cognition, mood, and behavior. Endogenous cannabinoid-like
compounds are released from pyramidal neurons with a high degree of
spatial and temporal specificity and travel backwards across the synapse
to regulate GABA release from presynaptic terminals. Little is known,
however, about the physiological role of this endogenous system. Our
current strategy combines electrophysiological, biochemical,
pharmacological, and optical imaging techniques to: 1) determine the
neuronal activity patterns that induce the release of endogenous
cannabinoids, 2) identify the specific inhibitory inputs to pyramidal
cells that are modulated by cannabinoids, and 3) investigate the
consequences of cannabinoid signaling on synaptic integration in
cortical circuits.
Nerve Growth Factors: NGF and related members of the
neurotrophin gene family play critical roles in nervous system
development by promoting cell survival and differentiation. These
factors have also been implicated in the pathophysiologic mechanisms
underlying Alzheimer’s and other neurodegenerative diseases. Recently it
has been shown that neurotrophins have potent effects as synaptic
modulators as well. In particular, we have found that BDNF
(brain-derived neurotrophic factor) regulates synaptic transmission and
plasticity by modulating the activity of both NMDA receptors and GABA
receptors in the hippocampus. We are exploring this phenomenon at the
biochemical, single channel, and synaptic circuit level. Ongoing
projects aim to characterize the underlying molecular signaling cascades
and define the functional roles of neurotrophin-induced plasticity
within the hippocampus and neocortex.
Lab Rotation Projects:
My lab is currently studying the roles of endogenous cannabinoids
and nerve growth factors in forms of synaptic plasticity that are
important for learning and memory. Students are welcome to develop novel
experimental ideas related to the physiology and/or pharmacology of
these neuromodulatory systems. In addition, the following specific
projects are available:
#1 - Effects of endogenous cannabinoids on the activity of
neocortical interneurons. Recent work from our lab has shown that
endogenous cannabinoids in the neocortex regulate the release of the
neurotransmitter GABA from synaptic terminals. We do not know if
cannabinoids also regulate the firing patterns of the GABA-containing
neurons. This project will involve learning patch clamp
electrophysiology and calcium imaging using slices of mouse neocortex to
examine the effects of cannabinoids on the activity of GABA interneurons.
#2 - Another area of interest in my lab involves the role of
brain-derived neurotrophic factor (BDNF) in synaptic transmission and
its interactions with drugs of abuse. This project will involve patch
clamp recordings from brain slices to examine the effects of BDNF in
regulating NMDA receptor-mediated synaptic plasticity in the neocortex,
and its potential interactions with ethanol and cannabinoids.
Laboratory Homepage
Publications
Selected Publications:
Fogal, B., Trettel, J., Uliasz, T. F., Levine, E. S., and Hewett, S. J.
(2005) Changes in secondary glutamate release underlie the developmental
regulation of excitotoxic neuronal cell death, Neuroscience, 132:
929-942.
Kolb, J. E., Trettel, J. and Levine, E. S. (2005) BDNF enhancement of
postsynaptic NMDA receptors is blocked by ethanol. Synapse, 55: 52-57.
Fortin, D. A., Trettel, J. and Levine, E. S. (2004) Brief trains of
action potentials enhance pyramidal neuron excitability via
endocannabinoid-mediated suppression of inhibition. J Neurophysiology,
92:2105-2112.
Trettel, J., Fortin, D. A. and Levine, E. S. (2004) Endocannabinoid
signalling selectively targets perisomatic inhibitory inputs to
pyramidal neurones in juvenile mouse neocortex. J. Physiology, 556:
95-107.
Trettel, J. and Levine, E. S. (2003) Endocannabinoids mediate rapid
retrograde signaling at interneuron-pyramidal neuron synapses of the
neocortex. J. Neurophysiology, 89: 2334-2338.
Trettel, J. and Levine, E. S. (2002) Cannabinoids depress inhibitory
synaptic inputs received by layer 2/3 pyramidal neurons of the neocortex.
J. Neurophysiology, 88: 534-539. |
