Experience-Dependent Gene Expression in the Rat Hippocampus after Spatial Learning: A Comparison of the Immediate-Early GenesArc, c-fos, andzif268

Abstract

Neuronal immediate-early gene (IEG) expression is regulated by synaptic activity and plays an important role in the neuroplastic mechanisms critical to memory consolidation. IEGs can be divided into two functional classes: (1) regulatory transcription factors (RTFs), which can broadly influence cell function depending on the "downstream" genes they regulate, and (2) "effector" proteins, which may directly modulate specific cellular functions. The objective of the current study was to determine whether the expression of an effector IEG (Arc) was similar to, or different from, that of two well characterized RTF IEGs (c-fos and zif268) after learning. IEG RNA levels from rats trained in spatial and nonspatial water tasks were determined using RNase protection assays and in situ hybridization. Overall, the regulation of the three IEGs was similar in the hippocampus and the entorhinal and primary visual cortices. Consequently, IEG RNA levels were positively correlated within a structure. By contrast, Arc and zif268 RNA levels were not correlated or only weakly correlated across structures, although c-fos RNA levels were moderately correlated across structures. Arc RNA expression differed from that of zif268 and c-fos in two regards: (1) hippocampal Arc RNA levels were correlated with learning of the hippocampal-dependent spatial, but not hippocampal-independent cued response, water task, and (2) Arc RNA levels in the hippocampus and entorhinal cortex increased after spatial reversal learning relative to an asymptotic performance group. Thus, although the expression of Arc, zif268, and c-fos exhibited many similarities, Arc was most responsive to differences in behavioral task demands.

Effects of Skilled Training on Sleep Slow Wave Activity and Cortical Gene Expression in the Rat

“…22 Learning a spatial water maze task, or a lever-press task, also increases Arc levels, and Arc induction is stronger in newly trained relative to overtrained or pseudotrained animals. 23,24 Spatial exploration also increases Arc expression, and does so specifically in glutamatergic neurons of hippocampus and neocortex. 58 Thus, the increased expression of Fos and Arc during training may reflect not just neuronal activation, but more specifically synaptic plasticity.…”

“…[19][20][21] We asked whether SWA shows a local increase in the trained motor cortex after learning to reach. Moreover, we examined whether skilled reaching increases the expression of Arc and Fos, 2 activity-dependent proteins involved in motor learning, [22][23][24] and whether this activation is specific for the trained motor area relative to other cortical areas.…”

Relapse to cocaine seeking increases activity-regulated gene expression differentially in the prefrontal cortex of abstinent rats

“…BDNF promotes synaptic plasticity and synaptic consolidation that are dependent upon the transcription and translation of arc (Kang and Schuman 1996;Guzowski et al 2001;Messaoudi et al 2002;Bramham and Messaoudi 2005;Soule et al 2006;Wibrand et al 2006). Thus, an increase in bdnf mRNA in the cortex may drive the arc response by initiating translation of newly synthesized arc mRNA in activated dendritic spines (Yin et al 2002;Ying et al 2002).…”

The exclusive induction of extinction is gated by BDNF

“…Evidence suggests that transient activations in TrkB signaling may initiate extinction. Consistent with this idea, compared to short recall conditions, Arc expression is constrained after prolonged exposures to the CS that lead to the extinction of CFM (Barnes and Thomas 2008;Mamiya et al 2009; see also Guzowski et al 2001). In addition, experimental conditions that reduce endogenous mBDNF levels in the hippocampus potentiate extinction of CFM (Barnes and Thomas 2008).…”