Experience-Dependent Plasticity of Mouse Visual Cortex in the Absence of the Neuronal Activity-Dependent Markeregr1/zif268

Abstract

Neuronal activity elicits a rapid increase in the expression of several immediate early genes (IEGs). To clarify a role for IEG response in activity-dependent development, we examined the contribution of the egr1/zif268 gene during visual cortical processing and plasticity in mice. We first analyzed the expression of egr1 mRNA in wild-type (WT) mice using Northern blot hybridization. In the visual cortex, expression of egr1 mRNA increased dramatically after eye opening, systemic injection of kainate, or 30 min of photostimulation after a brief (5 d) period of dark adaptation. Thus, the expression of egr1 is regulated by synaptic activity in the mouse visual cortex, as it is in other species (e.g., monkeys, cats, and rats). To evaluate whether this transcription factor is directly involved in activity-dependent plasticity, mice lacking Egr1 were deprived of the use of one eye during the developmental critical period [postnatal day 24 (P24)-P34]. Extracellular in vivo single-unit recordings from the binocular zone of the visual cortex revealed that visual responses developed normally in egr1 knock-out (KO) mice. Moreover, a similarly significant shift of responsiveness in favor of the open eye was produced in both KO and WT mice by either brief (4 d) or long-term (>2 weeks) occlusion of one eye. There was no apparent compensation among egr2, egr3, or c-fos mRNA and protein expression in the visual cortex of egr1 KO mice. Taken together, these results indicate that egr1 is a useful marker of sensory input in mice but is not intrinsically necessary for the experience-dependent plasticity of the visual cortex. Our findings underscore a mechanistic distinction between sensory plasticity and long-lasting forms of synaptic potentiation in the hippocampus, for which egr1/zif268 was recently found to be essential.

The mouse vesicular inhibitory amino acid transporter gene: Expression during embryogenesis, analysis of its core promoter in neural stem cells and a reconsideration of its alternate splicing

“…Our sequence analysis also found a well-conserved consensus binding site for Egr-1 within the CG rich region. Egr-1 has many roles including the regulation of neuronal genes in response to neuronal activity and its expression is strongly activated during neuronal differentiation in vivo and in our ES cell differentiation system (Mataga et al, 2001;McMahon et al, 1990 and data not shown). This suggests that this factor may be involved in the upregulation of the Viaat core promoter during differentiation.…”

Separable features of visual cortical plasticity revealed by N -methyl- d -aspartate receptor 2A signaling

“…Candidate plasticity factors have often been linked to a critical-period mechanism by DR (1). Yet simply because a molecule is regulated by activity does not mean that it is involved in plasticity, as shown recently for the immediate early gene zif268 (38). Both DR that is too short to prolong the critical period (12)(13)(14) and DR after visual experience has already begun (48) can still regulate expression of NR2A, which is most consistent with plasticity for orientation lasting into adulthood (49,50).…”

“…For Western blot analysis, visual cortices from halothane-anesthetized WT mice were dissected and homogenized by sonication (38). Total protein concentrations were determined by colorimetric (Bradford) assay system (Bio-Rad) and used to normalize loading.…”

Permissive proteolytic activity for visual cortical plasticity

“…As a further measure of neuronal activation, we quantified expression of the sensory marker egr-1͞zif268 (25), an immediate early gene whose response is up-regulated in GAD65 KO mouse visual cortex (18). In WT animals (Fig.…”