title: Deficit in sustained attention following selective cholinergic lesion of the pedunculopontine tegmental nucleus in rat, as measured with both post-mortem immunocytochemistry and in vivo PET imaging with [¹⁸F]fluoroethoxybenzovesamicol.
abstract: Cholinergic neurons of the pedunculopontine tegmental nucleus (PPTg) are thought to be involved in cognitive functions such as sustained attention, and lesions of these cells have been documented in patients showing fluctuations of attention such as in Parkinson's disease or dementia with Lewy Body. Animal studies have been conducted to support the role of these cells in attention, but the lesions induced in these animals were not specific to the cholinergic PPTg system, and were assessed by post-mortem methods remotely performed from the in vivo behavioral assessments. Moreover, sustained attention have not been directly assessed in these studies, but rather deduced from indirect measurements. In the present study, rats were assessed on the 5-Choice Serial Reaction Time Task (5-CSRTT), and a specific measure of variability in response latency was created. Animals were observed both before and after selective lesion of the PPTg cholinergic neurons. Brain cholinergic denervation was assessed both in vivo and ex vivo, using PET imaging with [(18)F]fluoroethoxybenzovesamicol ([(18)F]FEOBV) and immunocytochemistry respectively. Results showed that the number of correct responses and variability in response latency in the 5-CSRTT were the only behavioral measures affected following the lesions. These measures were found to correlate significantly with the number of PPTg cholinergic cells, as measured with both [(18)F]FEOBV and immunocytochemistry. This suggests the primary role of the PPTg cholinergic cells in sustained attention. It also allows to reliably use the PET imaging with [(18)F]FEOBV for the purpose of assessing the relationship between behavior and cholinergic innervation in living animals.
authors.affiliation: Université du Québec à Montréal (UQAM), Canada; Douglas Mental Health University Institute, Canada.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Cyr
authors.affiliation: Université du Québec à Montréal (UQAM), Canada; Douglas Mental Health University Institute, Canada.
authors.forename: Maxime J
authors.initials: MJ
authors.lastname: Parent
authors.affiliation: Douglas Mental Health University Institute, Canada.
authors.forename: Naguib
authors.initials: N
authors.lastname: Mechawar
authors.affiliation: Douglas Mental Health University Institute, Canada; Montreal Neurological Institute (MNI), Canada.
authors.forename: Pedro
authors.initials: P
authors.lastname: Rosa-Neto
authors.affiliation: Montreal Neurological Institute (MNI), Canada.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soucy
authors.affiliation: University at Buffalo, USA.
authors.forename: Stewart D
authors.initials: SD
authors.lastname: Clark
authors.affiliation: Université du Québec à Montréal (UQAM), Canada.
authors.forename: Meghmik
authors.initials: M
authors.lastname: Aghourian
authors.affiliation: Université du Québec à Montréal (UQAM), Canada; Douglas Mental Health University Institute, Canada; Montreal Neurological Institute (MNI), Canada. Electronic address: bedard.marc-andre@uqam.ca.
authors.forename: Marc-Andre
authors.initials: MA
authors.lastname: Bedard
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000000981:diagnostic imaging*; D001344:Autopsy; D002795:Choline O-Acetyltransferase; D059329:Cholinergic Neurons / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D008297:Male; D009498:Neurotoxins / Q000633:toxicity; D045042:Pedunculopontine Tegmental Nucleus / Q000293:injuries*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010880:Piperidines / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013223:Statistics as Topic; D013997:Time Factors
chemical_list: D009498:Neurotoxins; D010880:Piperidines; C116169:fluoroethoxy-benzovesamicol; D019788:Fluorodeoxyglucose F18; D002795:Choline O-Acetyltransferase; D010751:Phosphopyruvate Hydratase
keywords: 5-Choice Serial Reaction Time Task (5-CSRTT); Acetylcholine; Attention; Immunocytochemistry; Pedunculopontine tegmental nucleus (PPTg); Positron emission tomography (PET); [(18)F]FEOBV; [(18)F]fluoroethoxybenzovesamicol