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Abstract
Dopamine (DA) is a key neurotransmitter involved in multiple physiological functions including motor control, modulation of affective and emotional states, reward mechanisms, reinforcement of behavior, and selected higher cognitive functions. Dysfunction in dopaminergic transmission is recognized as a core alteration in several devastating neurological and psychiatric disorders, including Parkinson’s disease (PD), schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD) and addiction. Here we will discuss the current insights on the role of DA in motor control and reward learning mechanisms and its involvement in the modulation of synaptic dynamics through different pathways. In particular, we will consider the role of DA as neuromodulator of two forms of synaptic plasticity, known as long-term potentiation (LTP) and long-term depression (LTD) in several cortical and subcortical areas. Finally, we will delineate how the effect of DA on dendritic spines places this molecule at the interface between the motor and the cognitive systems. Specifically, we will be focusing on PD, vascular dementia, and schizophrenia.
Highlights
In the mammalian brain, the dopaminergic (DAergic) systems play a central role in controlling movement, hormone release, emotional balance, reward, odor discrimination and vision.DAergic neurons are anatomically and functionally heterogeneous, located in the telencephalon, [dispersed within the glomerular layer of the olfactory bluband the amacrine cell population of the retina, in the diencephalon where it negatively regulates the production of prolactin, which innervate the superior olivary complex and the inferior colliculus in the brain stem where it is supposed to regulate auditory processing
Gs/olf proteins that stimulate adenylate cyclase (AC), the enzyme that converts adenosine triphosphate (ATP) into cyclic adenosine monophosphate and increase cAMP production. The latter activates protein kinase A (PKA), which in turn phosphorylates c-AMP response element-binding protein (CREB), which is translocated into the nucleus activating CREB-dependent transcription of genes involved in synaptic plasticity
We showed that important motor learning processes in cortical and subcortical neural systems, such as the basal ganglia are sustained by spine complexity along dendrites and their remodeling; the latter being a possible general feature associated with the structural plasticity underlying processes such as long-term memory maintenance, reward, motivation, and goal-directed behavior, exerted by the DAergic system [127]
Summary
The dopaminergic (DAergic) systems play a central role in controlling movement, hormone release, emotional balance, reward, odor discrimination and vision. The development of mDAergic neurons in vivo is a highly coordinated and complex process involving events ranging from neurulation, proliferation and differentiation of progenitor cells to migration, formation of synapse and neural circuits. The external signals such as morphogens and growth factors, activation of specific gene cascades and cellular interactions involved in the specification, differentiation and maturation of DAergic function have been discussed elsewhere (for extensive reviews see [6,7,8,9,10,11,12,13,14]). The disorder was known since antiquity and already treated with the seeds of a legume plant (Mucuna pruriens) that contains the therapeutic levels of what is known as levodopa, used in Parkinson’s disease (PD) treatment
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