Univesity of Maryland: Department of Biology
University of Maryland
ELIZABETH M. QUINLAN
Associate Professor
email:equinlan@umd.eduphone:
301.405.7396 (office)
301.405.7222 (lab)
fax:301.314.9358
office:1110 Bioscience Research Building
graduate programs: Biology, C-CEBH, NACS
visit lab page most recent publicationsRESEARCH 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.
Recent Publications
He HY, Ray B, Dennis K, Quinlan EM. Experience-dependent recovery of vision following chronic deprivation amblyopia. Nat Neurosci. 2007 Sep;10(9):1134-6. Epub 2007 Aug 12.
He HY, Hodos W, Quinlan EM. Visual deprivation reactivates rapid ocular dominance plasticity in adult visual cortex. J Neurosci. 2006 Mar 15;26(11):2951-5.
He HY, Rasmusson DD, Quinlan EM. Progressive elevations in AMPA and GABAA receptor levels in deafferented somatosensory cortex. J Neurochem. 2004 Sep;90(5):1186-93.
Quinlan EM, Lebel D, Brosh I, Barkai E. A molecular mechanism for stabilization of learning-induced synaptic modifications. Neuron. 2004 Jan 22;41(2):185-92.