Elizabeth M. Quinlan,
Ph.D.
Assistant
Professor
Department
of Biology
Neuroscience
and Cognitive
Sciences Program
University of
Maryland
College Park, MD 20742
Email: equinlan@umd.edu
Research Interests
:
Reactivation
of ocular dominance plasticity in the adult visual cortex
The ocular dominance shift observed
in response to monocular deprivation is a sensitive assay of the level
of synaptic plasticity available to synapses in the binocular visual cortex. Depriving one eye
of vision induces a shift in ocular dominance towards the non-deprived eye .
In juvenile rats, brief
(<3 days) monocular deprivation induces a rapid depression of the response to stimulation of the deprived
eye, followed by a slower potentiation of the response to stimulation of the
non-deprived eye. In adults,
brief monocular deprivation does not induce an ocular dominance shift.
We have recently demonstrated that
ocular dominance plasticity can be reactivated in adult rat visual cortex
by visual deprivation. Following visual deprivation, brief (3 days) of monocular
deprivation induces an ocular dominance
shift, due to a rapid depression of the response to stimulation of the deprived eye and a simultaneous
potentiation of the response to stimulation of the non-deprived eye. The enhanced
ocular dominance plasticity induced by visual deprivation persists for days, even
if binocular vision precedes monocular deprivation. When monocular deprivation
begins at eye opening at proceeds until adulthood, reverse occlusion is
ineffective at recovering function in the deprived eye. However, reverse
occlusion successfully reverses the effects of lifelong monocular deprivation if
performed following a period of visual deprivation. We are currently
exploring the utility of visual deprivation to enhance the cortical
response to reverse occlusion. Visual deprivation also
induces a significant
decrease in the level of GABAARs relative to AMPARs, and a return to the juvenile form of NMDARs in the visual
cortex, two molecular changes that we propose enable the reactivation of
ocular dominance plasticity in the adult visual cortex.
Use of Egr-1 chromatin
immunoprecipitation to identify late response genes induced in the
mouse visual cortex by visual experience.
Synaptic plasticity in the visual
cortex (VCtx) is robust in juveniles, but decreases with age. The
developmental decrease in synaptic plasticity is driven by visual
experience and can be prevented by dark rearing (DR) from birth.
However, bringing a DR animal into the light induces rapid
experience-dependent maturation of the visual system and a parallel
decrease in synaptic plasticity in the visual cortex. Egr1 is an
inducible immediate-early gene transcription factor that is
up-regulated over time during the development of the VCtx. DR
inhibits the developmental increase in Egr1 while brief light exposure
(LE) induces a significant increase in Egr1 protein. In order to
understand how inducible regulation of transcription is coupled to
long-term changes in synaptic function, we have developed a technique
that is a modification of chromatin immunoprecipitation (ChIP) to
identify Egr1 target genes. While traditional ChIPs uses
antibodies against acetylated histones to IP actively transcribed DNA,
we used an antibody against Egr1 to IP candidate late response genes
transcribed in response to light exposure. Egr1 ChIPs
immunoprecipitates known targets of Egr1 (synapsin) but not negative
controls (VAMP). By combining egr1 ChIPs with random primed PCR,
we have identified a several late response genes, including PABPn1 and
Plau, that are transcribed in response to light exposure. We are
currently exploring the role of each of these egr1 target genes in
expereince-dependent synaptic plasticity in the mammalian cortex.
Lab Members:
Michael Cloud - Faculty Research
Assistant nihil1318@hotmail.com
Lindsey L. Scott, Ph.D.
- Postdoctoral Fellow llscott@wam.umd.edu
Haiyan He, M.S. - Ph.D.
student
hehaiyan@wam.umd.edu
Philip Wang - Ph.D.
student wangph@umd.edu
Dana Carmichael, M.S. - Ph.D. student daerosea@hotmail.com
Sean Sheffler-Collins - Undergraduate
Howard Hughes Research Fellow
seansc@wam.umd.edu
Dana Kogan - Undergraduate Howard Hughes
Research Fellow sublimegrl94@yahoo.com
Rishi Sidhu: Undergraduate
research assistant nishchal@umd.edu
RELATED
PUBLICATIONS
He HY, Hodos W, Quinlan EM. (2006) Visual deprivation reactivates rapid
ocular dominance plasticity in adult visual cortex. J Neurosci.
26:2951-5.
Castellani GC, Quinlan EM, Bersani F, Cooper LN, Shouval HZ. (2005) A
model of bidirectional synaptic plasticity: from signaling network to
channel conductance. Learn Mem. 12:423-32.
He HY, Rasmusson DD, Quinlan EM. (2004) Progressive elevations in AMPA
and GABAA receptor levels in deafferented somatosensory cortex. J
Neurochem. 90:1186-93.
Quinlan EM, Lebel D, Brosh I, Barkai E. (2004) A molecular mechanism
for stabilization of learning-induced synaptic modifications.
Neuron. 41:185-92.
Brauth S, Liang W, Roberts TF, Scott LL, Quinlan EM. (2002) Contact
call-driven Zenk protein induction and habituation in telencephalic
auditory pathways in the Budgerigar (Melopsittacus undulatus):
implications for understanding vocal learning processes. Learn Mem.
9:76-88.
Morishita W, Connor JH, Xia H, Quinlan EM, Shenolikar S, Malenka RC.
(2001) Regulation of synaptic strength by protein phosphatase 1.
Neuron. 32:1133-48.
Wells DG, Dong X, Quinlan EM, Huang YS, Bear MF, Richter JD, Fallon JR.
(2001) A role for the cytoplasmic polyadenylation element in NMDA
receptor-regulated mRNA translation in neurons. J Neurosci.
21:9541-8.
Castellani GC, Quinlan EM, Cooper LN, Shouval HZ. (2001) A biophysical
model of bidirectional synaptic plasticity: dependence on AMPA and NMDA
receptors. Proc Natl Acad Sci U S A. 98:12772-7.
Heynen AJ, Quinlan EM, Bae DC, Bear MF. (1999) Bidirectional,
activity-dependent regulation of glutamate receptors in the adult
hippocampus in vivo. Neuron.28:527-36.
Quinlan EM, Olstein DH, Bear MF. (1999) Bidirectional,
experience-dependent regulation of N-methyl-D-aspartate receptor
subunit composition in the rat visual cortex during postnatal
development. Proc Natl Acad Sci U S A. 96:12876-80.
Quinlan EM, Philpot BD, Huganir RL, Bear MF. (1999) Rapid,
experience-dependent expression of synaptic NMDA receptors in visual
cortex in vivo. Nat Neurosci. 2:352-7.
Revised 4/15/06