Areas of Interest
My laboratory studies synaptic modulation in the hippocampus
and neocortex. Our recent work has focused on the physiologic
roles of endogenous cannabinoids and nerve growth factors in
various forms of synaptic plasticity that are important for
learning and memory. We are exploring these phenomena 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 cannabinoid-growth
factor interactions in the neocortex.
Another area of interest in the lab focuses on understanding
the neuronal and synaptic deficits in autism and related
neurogenetic disorders. This project involves electrical
recordings, calcium imaging, and immunocytochemical analysis of
human brain neurons grown in culture. In collaboration with Dr.
Marc Lalande’s lab, these studies use inducible pluripotent stem
cells (iPS cells) that are derived from human skin cells and
then reprogrammed to differentiate into neurons. We are
interesting in comparing the functional properties and
expression patterns of neurons from patients with autism or
Angelman’s Syndrome vs. healthy controls.
We also have an ongoing collaboration with the lab of Dr.
Richard Mains and Dr. Betty Eipper to study the role of Kalirin,
a family of proteins that regulates synaptic structure and
function. This project involves a combination of morphological,
biochemical, electrophysiological, and behavioral analyses of
mice with a conditional knockout of the Kalirin-7 gene. We are
particularly interested in the role of Kalirin in shaping the
behavior of dendritic spines.
Lab Rotation Projects
One potential rotation project is to examine the interaction
between cannabinoids and nerve growth factors in the rodent
neocortex. Specifically, this project will introduce the student
to patch clamp recording techniques, intracellular calcium
imaging, and RNA interference methods in brain slices to
determine how cannabinoids regulate growth factor production and
explore the functional relevance of this interaction at cortical
synapses.
Another project involves recording the electrical activity
and monitoring intracellular calcium dynamics from human stem
cell-derived brain neurons grown in culture. We are interested
in characterizing the functional properties, protein expression
patterns, and synaptic connections from neurons derived from
patients with autism and other neurogenetic disorders and
identifying underlying deficits that may be related to disease
phenotype.
Publications
Selected Publications
Madara J.C. and Levine E.S. (2008) Presynaptic and
postsynaptic NMDA receptors mediate distinct effects of
brain-derived neurotrophic factor on synaptic transmission. J
Neurophysiology 100: 3175-84.
Ma X.M., Kiraly D.D., Gaier E.D., Wang Y., Kim E.J., Levine
E.S., Eipper B.A. and Mains R.E. (2008) Kalirin-7 is required
for synaptic structure and function. J Neuroscience 28:
12368-82.
Fortin D.A. and Levine E. S. (2007) Differential effects of
endocannabinoids on glutamatergic and GABAergic inputs to layer
5 pyramidal neurons. Cerebral Cortex, 17: 163-174.
Lemtiri-Chlieh F. and Levine E.S. (2007) Lack of
depolarization-induced suppression of inhibition (DSI) in layer
2/3 interneurons that receive cannabinoid-sensitive inhibitory
inputs. J Neurophysiol 98: 2517-2524.
 View more publications, see
Pubmed listing. |
