Abstract
With its capacity to modulate motor control and motivational as well as cognitive functions dopamine is implicated in numerous neuropsychiatric diseases. The present study investigated whether an imbalance in dopamine homeostasis as evident in the dopamine overexpressing rat model (DAT-tg), results in learning and memory deficits associated with changes in adult hippocampal neurogenesis. Adult DAT-tg and control rats were subjected to the Morris water maze, the radial arm maze and a discrimination reversal paradigm and newly generated neurons in hippocampal circuitry were investigated post mortem. DAT-tg rats were found to exhibit a striking inability to acquire information and deploy spatial search strategies. At the same time, reduced integration of adult-born neurons in hippocampal circuitry was observed, which together with changes in striatal dopamine signalling might explain behavioural deficits.
Highlights
Midbrain neurons located in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA)[1] provide a ‘tonic’ baseline level and ‘phasic’ large changes of dopamine (DA) concentrations to downstream cortical and subcortical structures[2,3]
Animal studies demonstrate that hippocampal oscillatory activity increases during place learning and that hippocampal-striatal coherence appears after training, a mechanism considered necessary in switching from place learning to the usage of a proper response strategy[19]
In comparison dopamine transporter (DAT)-tg animals showed a significantly lower rate of successful navigation to the platform (trial: F(6.8,171) = 3.516, p = 0.002; genotype: (F(1, 25) = 181.2, p < 0.001; trial × genotype interaction: F(6.8, 171) = 3.941, p = 0.001; repeated measures ANOVA) and none of the dopamine transporter overexpressing rats (DAT-tg) animals has been found to reach the platform above chance level (Fig. 2d)
Summary
Midbrain neurons located in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA)[1] provide a ‘tonic’ baseline level and ‘phasic’ large changes of dopamine (DA) concentrations to downstream cortical and subcortical structures[2,3]. Hippocampal and striatal memory systems have long been thought to operate independently. DA modulates ontogenetic neurogenesis[22], in the adult brain DA fibres directly target subventricular zone (SVZ) and subgranular zone (SGZ) neuronal precursors[23,24] expressing DA receptors[24,25,26]. In this line ablation of midbrain DA neurons in rodents, results in reduced adult neurogenesis both in striatum and hippocampus[24,27]
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