Differences in the Flexibility of Switching Learning Strategies and CREB Phosphorylation Levels in Prefrontal Cortex, Dorsal Striatum and Hippocampus in Two Inbred Strains of Mice

Abstract

Flexibility in using different learning strategies was assessed in two different inbred strains of mice, the C57BL/6 and DBA/2 strains. Mice were trained sequentially in two different Morris water maze protocols that tested their ability to switch their learning strategy to complete a new task after first being trained in a different task. Training consisted either of visible platform trials (cued training) followed by subsequent hidden platform trials (place training) or the reverse sequence (place training followed by cued training). Both strains of mice showed equivalent performance in the type of training (cued or place) that they received first. However, C57BL/6 mice showed significantly better performances than DBA/2 mice following the switch in training protocols, irrespective of the order of training. After completion of the switched training session, levels of cAMP response element-binding protein (CREB) and phosphorylated CREB (pCREB) were measured in the hippocampus, striatum and prefrontal cortex of the mice. Prefrontal cortical and hippocampal pCREB levels differed by strain, with higher levels found in C57BL/6 mice than in DBA/2 mice. No strain differences were observed in the medial or lateral region of the dorsal striatum. These findings indicate that the engagement (i.e., CREB signaling) of relevant neural structures may vary by the specific demands of the learning strategy, and this is closely tied to differences in the flexibility of C57BL/6 and DBA/2 mice to switch their learning strategies when given a new task.

Unpredictable chronic mild stress differentially impairs social and contextual discrimination learning in two inbred mouse strains

“…Studies have shown DBA mice to have reduced persistence of hippocampal long-term potentiation (LTP) when compared to BL6 mice, as well as reduced levels of signalling proteins such as protein kinase C (PKC) [ 63 , 96 ]. Furthermore, DBA mice exert reduced levels of cAMP response element-binding protein (CREB), a transcription factor associated with long-term memory formation, in prefrontal cortex and hippocampus when compared to BL6 mice [ 97 ]. These differences manifest themselves in cognitive performances where strain-dependent differences have been observed in various spatial memory and contextual conditioning tasks.…”

“…UCMS is a well-established rodent model for stress-related psychopathologies, displaying changes at the molecular, anatomical, and behavioral level comparable to clinical observations [ 10 , 44 – 49 ]. The inbred strains C57BL/6J and DBA/2J are frequently used and have been shown to differ in their reaction to stressful manipulations [ 50 ], social and cognitive behavior [ 51 , 52 ], HC and PFC synaptic plasticity [ 53 , 54 ], as well as in their DAergic profile [ 55 ]. The goal of these experiments was to investigate the impact of genetic background on stress-induced social and cognitive impairments and how this correlates with the expression levels in the HC and PFC of genes implicated in dopaminergic neurotransmission and neuronal plasticity.…”

4-Hydroxynonenal Immunoreactivity Is Increased in the Frontal Cortex of 5XFAD Transgenic Mice

“…Each mouse serially received a cued/response and place/spatial version of the water maze task, adopted from McDonald and White [14] and modified in our previous studies [17,[19][20][21]. Briefly, each mouse received cued/response training for 4 days, followed by place/spatial training for four days.…”

“…Relevant neural structures are engaged by the specific demands of the learning strategy [14][15][16][17]. For example, in the water maze task, a place/spatial learning (place) strategy requiring the use of spatial cues depends critically on the hippocampus, whereas a cued/response (cued) learning strategy using egocentric navigation/instrumental learning relies on the striatum.…”

Superior Place Learning of C57BL/6 vs. DBA/2 Mice Following Prior Cued Learning in the Water Maze Depends on Prefrontal Cortical Subregions

“…C57BL/6 mice have been reported to show better performance in hippocampal-dependent tasks than DBA/2 mice (Paylor et al, 1994; Passino et al, 2002; Sung et al, 2008). Furthermore, C57BL/6 mice performed better than DBA/2 mice in a task that required switching between cued learning and place learning (Cho and Han, 2016). These behavioral differences were closely tied to strain differences in phosphorylated cAMP response element binding protein phosphorylated CREB (pCREB) levels in the PFC (Cho and Han, 2016).…”