Distinct Changes in CREB Phosphorylation in Frontal Cortex and Striatum During Contingent and Non-Contingent Performance of a Visual Attention Task

Abstract

The cyclic-adenosine monophosphate response element-binding protein (CREB) family of transcription factors has been implicated in numerous forms of behavioral plasticity. We investigated CREB phosphorylation along some nodes of corticostriatal circuitry such as frontal cortex (FC) and dorsal (caudate–putamen, CPu) and ventral (nucleus accumbens, NAC) striatum in response to the contingent or non-contingent performance of the five-choice serial reaction time task (5-CSRTT) used to assess visuospatial attention. Three experimental manipulations were used; an attentional performance group (contingent, “master”), a group trained previously on the task but for whom the instrumental contingency coupling responding with stimulus detection and reward was abolished (non-contingent, “yoked”) and a control group matched for food deprivation and exposure to the test apparatus (untrained). Rats trained on the 5-CSRTT (both master and yoked) had higher levels of CREB protein in the FC, CPu, and NAC compared to untrained controls. Despite the divergent behavior of “master” and “yoked” rats CREB activity in the FC was not substantially different. In rats performing the 5-CSRTT (“master”), CREB activity was completely abolished in the CPu whereas in the NAC it remained unchanged. In contrast, CREB phosphorylation in CPu and NAC increased only when the contingency changed from goal-dependent to goal-independent reinforcement (“yoked”). The present results indicate that up-regulation of CREB protein expression across cortical and striatal regions possibly reflects the extensive instrumental learning and performance whereas increased CREB activity in striatal regions may signal the unexpected change in the relationship between instrumental action and reinforcement.

Preliminary investigation of the influence of CREB1 gene polymorphisms on cognitive dysfunction in Chinese patients with major depression

“…Pozzi and colleagues [56] found that the upregulation of the CREB protein across cortical and striatal subregions might reflect the extensive instrumental performance acquisition of the five-choice serial reaction time task (5-CSRTT), which is a visuospatial attention assessment tool. The authors [57] suggested that attention dysfunctions might be associated with the phosphorylation of the transcription factor CREB on residue S 133 in the frontal cortex (FC).…”

Cross-Sectional and Longitudinal Effects of CREB1 Genotypes on Individual Differences in Memory and Executive Function: Findings from the BLSA

“…Identifying genetic factors that contribute to interindividual variability in performance and age-related decline of specific cognitive functions can inform us about the underlying neuromolecular networks. Genetic variations in the CREB1 gene (HGNC: 2345) are of interest because CREB signaling pathways, by regulating gene expression, contribute to the adaptation of neuronal properties in brain regions important for memory and executive functions ( Benito and Barco, 2010 ; Rapanelli et al, 2010 ; Pozzi et al, 2011 ; Sanchez-Huertas and Rico, 2011 ; Leckie et al, 2014 ). Memory and executive function are susceptible to age-related decline and early neurodegeneration ( Ronnlund et al, 2005 ; Grober et al, 2008 ; Goh et al, 2012 ; Weintraub et al, 2012 ).…”

Neuronal signaling and behavior

“…The Original Article by Pozzi et al ( 2011 ) provides evidence indicating that activation of the cAMP response element-binding protein (CREB), at different locations within the corticostriatal circuitry, is associated to distinct behavioral responses involved in visuospatial attention.…”