Acute Low Alcohol Disrupts Hippocampus-Striatum Neural Correlate of Learning Strategy by Inhibition of PKA/CREB Pathway in Rats

Abstract

The hippocampus and striatum guide place-strategy and response-strategy learning, respectively, and they have dissociable roles in memory systems, which could compensate in case of temporary or permanent damage. Although acute alcohol (AA) treatment had been shown to have adverse effects on hippocampal function, whether it causes the functional compensation and the underlying mechanisms is unknown. In this study, rats treated with a low dose of AA avoided a hippocampus-dependent spatial strategy, instead preferring a striatum-dependent response strategy. Consistently, the learning-induced increase in hippocampal, but not striatal, pCREB was rendered less pronounced due to diminished activity of pPKA, but not pERK or pCaMKII. As rats approached the turn-decision area, Sp-cAMP, a PKA activator, was found to mitigate the inhibitory effect of AA on intra- and cross-structure synchronized neuronal oscillations, and rescue response-strategy bias and spatial learning deficits. Our study provides strong evidence of the critical link between neural couplings and strategy selection. Moreover, the PKA/CREB-signaling pathway is involved in the suppressive effect of AA on neural correlates of place-learning strategy. The novel important evidence provided here shows the functional couplings between the hippocampus and striatum in spatial learning processing and suggests possible avenues for therapeutic intervention.

Effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice

“…The present VTA-dopamine biochemical data could be explained by the presence of amylin receptors on dopaminergic neurons in the VTA (Mietlicki-Baase et al 2015b ) and by the fact that sCT into the VTA reduces food reward-induced dopamine release in the rat NAc (Mietlicki-Baase et al 2015b ). The additional findings that sCT sub-chronic administration increases the levels of 3-MT in the NAc and decreases them in the dorsal striatum and reduces noradrenaline levels in the hippocampus of mice, areas of importance for alcohol behavioural responses (Di Chiara and Imperato 1986 ; Robbins and Everitt 2002 ; Sun et al 2018 ), could also contribute to the attenuated locomotor response to alcohol noted in our behavioural experiments. However, biochemical experiments in other brain areas, for example, those that are involved in motor functions, are warranted in the future.…”

Melamine disrupts spatial reversal learning and learning strategy via inhibiting hippocampal BDNF-mediated neural activity

“…The procedure was conducted as our previous studies with modification [ 46 , 47 ]. Briefly, the rat was placed in the start arm and allowed to visit the end of one of reward arms.…”

“…Rats were trained according to the versions of the cross-maze task [ 46 , 47 ]. Training was conducted in a black Plexiglas cross-maze consisting of 2 start arms (e.g., north and south arm) and 2 test (reward) arms (e.g., east and west arm).…”

“…The chambers contained two retractable levers located on either side of a central food trough. As previous studies [ 17 , 47 , 48 ], rats were trained daily 30-min sessions with one of two levers extended randomly when the cue light above the level was illuminated. The schedule was progressively changed according to the sequence fixed ratio (FR)-1, FR-15, FR-30, and finally FR-60.…”

“…Each cluster was then checked manually to ensure that the cluster boundaries were well separated, and waveform shapes were consistent with action potentials [ 57 , 58 ]. Units were then graded for quality and classified as pyramidal neurons and fast-spiking interneurons as previously described [ 46 , 47 ].…”