AUTHOR=Rizzi Giorgio , Tan Kelly R. 

TITLE=Dopamine and Acetylcholine, a Circuit Point of View in Parkinson’s Disease

JOURNAL=Frontiers in Neural Circuits

VOLUME=11

YEAR=2017

URL=https://www.frontiersin.org/journals/neural-circuits/articles/10.3389/fncir.2017.00110

DOI=10.3389/fncir.2017.00110

ISSN=1662-5110

ABSTRACT=<p>Data from the World Health Organization (National Institute on Aging, <xref ref-type="bibr" rid="B60">2011</xref>) and the National Institutes of Health (He et al., <xref ref-type="bibr" rid="B158">2016</xref>) predicts that while today the worldwide population over 65 years of age is estimated around 8.5%, this number will reach an astounding 17% by 2050. In this framework, solving current neurodegenerative diseases primarily associated with aging becomes more pressing than ever. In 2017, we celebrate a grim 200th anniversary since the very first description of Parkinson’s disease (PD) and its related symptomatology. Two centuries after this debilitating disease was first identified, finding a cure remains a hopeful goal rather than an attainable objective on the horizon. Tireless work has provided insight into the characterization and progression of the disease down to a molecular level. We now know that the main motor deficits associated with PD arise from the almost total loss of dopaminergic cells in the substantia nigra pars compacta. A concomitant loss of cholinergic cells entails a cognitive decline in these patients, and current therapies are only partially effective, often inducing side-effects after a prolonged treatment. This review covers some of the recent developments in the field of Basal Ganglia (BG) function in physiology and pathology, with a particular focus on the two main neuromodulatory systems known to be severely affected in PD, highlighting some of the remaining open question from three main stand points:</p><p>- Heterogeneity of midbrain dopamine neurons.</p><p>- Pairing of dopamine (DA) sub-circuits.</p><p>- Dopamine-Acetylcholine (ACh) interaction.</p><p>A vast amount of knowledge has been accumulated over the years from experimental conditions, but very little of it is reflected or used at a translational or clinical level. An initiative to implement the knowledge that is emerging from circuit-based approaches to tackle neurodegenerative disorders like PD will certainly be tremendously beneficial.</p>