| First Author | Swaminathan M | Year | 2019 |
| Journal | Neuroscience | Volume | 423 |
| Pages | 76-85 | PubMed ID | 31705886 |
| Mgi Jnum | J:285586 | Mgi Id | MGI:6391874 |
| Doi | 10.1016/j.neuroscience.2019.10.029 | Citation | Swaminathan M, et al. (2019) alpha-Synuclein Regulates Development and Function of Cholinergic Enteric Neurons in the Mouse Colon. Neuroscience 423:76-85 |
| abstractText | Alpha-Synuclein (alpha-Syn) is expressed in the central nervous system and the nervous system of the gut (enteric nervous system, ENS), and is well known to be the major constituent of Lewy bodies which are the hallmark of Parkinson's disease. Gastrointestinal disorders frequently manifest several years before motor deficits develop in Parkinson's patients. Despite extensive research on pathological rodent models, the physiological role of alpha-Syn in the normal ENS is unclear hampering analysis of its neuropathology. We compared the ENS in colons of alpha-Syn-knockout (alpha-Syn KO) and wild-type mice using immunohistochemistry and calcium-imaging of responses to synaptic input. We found that alpha-Syn is predominantly expressed in cholinergic varicosities, which contain vesicular acetylcholine transporter. alpha-Syn KO mice had higher enteric neuron density and a larger proportion of cholinergic neurons, notably those containing calretinin, demonstrating a role for alpha-Syn in regulating development of these neurons. Moreover, alpha-Syn deletion enhanced the amplitude of synaptically activated [Ca(2+)]i transients that are primarily mediated by acetylcholine activating nicotinic receptors suggesting that alpha-Syn modulates the availability of acetylcholine in enteric nerve terminals. |
