Abstract
Cerebral and cerebellar hemispheres are known to be asymmetrical in structure and function, and previous literature supports that asymmetry extends to the neural dopamine systems. Using in vivo fixed potential amperometry with carbon fiber microelectrodes in anesthetized mice, the current study assessed hemispheric lateralization of stimulation-evoked dopamine in the nucleus accumbens (NAc) and the influence of the cerebellum in regulating this reward-associated pathway. Our results suggest that cerebellar output can modulate mesolimbic dopamine transmission, and this modulation contributes to asymmetrically lateralized dopamine release. Dopamine release did not differ between hemispheres when evoked by medial forebrain bundle (MFB) stimulation; however, dopamine release was significantly greater in the right NAc relative to the left when evoked by electrical stimulation of the cerebellar dentate nucleus (DN). Furthermore, cross-hemispheric talk between the left and right cerebellar DN does not seem to influence mesolimbic release given that lidocaine infused into the DN opposite to the stimulated DN did not alter release. These studies may provide a neurochemical mechanism for studies identifying the cerebellum as a relevant node for reward, motivational behavior, saliency, and inhibitory control. An increased understanding of the lateralization of dopaminergic systems may reveal novel targets for pharmacological interventions in neuropathology of the cerebellum and extending projections.
Highlights
No longer considered a structure primarily for motor coordination, the cerebellum is known to contain three distinct regions that contribute to sensorimotor, limbic, and cognitive processes [1]
The current study assessed the hemispheric lateralization of stimulation-evoked dopamine in the nucleus accumbens (NAc) and the influence of the cerebellum in regulating this rewardaCC-BY 4.0 International license
Results from Experiment 1 show that the mesolimbic pathway itself is not responsible for asymmetrical lateralization of dopamine release, given that NAc dopamine release did not differ between hemispheres when evoked by ipsilateral medial forebrain bundle (MFB) stimulation
Summary
No longer considered a structure primarily for motor coordination, the cerebellum is known to contain three distinct regions that contribute to sensorimotor, limbic, and cognitive processes [1]. Imaging and lesion studies in humans have found the left cerebellar hemisphere to be involved in visuo-spatial operations [19,20,21,22], and a right cerebellar involvement in language processes [23,24,25] Related to these behaviorally-associated asymmetries, the bilateral hemispheres of the brain contain lateralized neurotransmitter systems in cortical and subcortical regions, and certain experiences have been shown to enhance this lateralization. Increased dopamine levels in the right prefrontal cortex of adult rats were found to be strongly correlated with anxiety responses in the elevated plus-maze test [27], and dopamine receptor blockade in the right mPFC but not the left mPFC of handled rats resulted in elevated stress and hormone levels [28] These studies provide evidence of hemispheric imbalance in the mesocorticolimbic dopamine system
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