Journal article
Scopolamine and Medial Frontal Stimulus-Processing during Interval Timing
Neuroscience, Vol.414, pp.219-227
08/21/2019
DOI: 10.1016/j.neuroscience.2019.07.004
PMCID: PMC7040457
PMID: 31299344
Abstract
Neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and Alzheimer's disease (AD) involve loss of cholinergic neurons in the basal forebrain. Here, we investigate how cholinergic dysfunction impacts the frontal cortex during interval timing, a process that can be impaired in PD and AD patients. Interval timing requires participants to estimate an interval of several seconds by making a motor response, and depends on the medial frontal cortex (MFC), which is richly innervated by basal forebrain cholinergic projections. Past work has shown that scopolamine, a muscarinic cholinergic receptor antagonist, reliably impairs interval timing. We tested the hypothesis that scopolamine would attenuate time-related ramping, a key form of temporal processing in the MFC. We recorded neuronal ensembles from eight mice during performance of a 12-s fixed-interval timing task, which was impaired by the administration of scopolamine. Consistent with past work, scopolamine impaired timing. To our surprise, we found that time-related ramping was unchanged, but stimulus-related activity was enhanced in the MFC. Principal component analyses revealed no consistent changes in time-related ramping components, but did reveal changes in higher components. Taken together, these data indicate that scopolamine changes stimulus processing rather than temporal processing in the MFC. These data could help understand how cholinergic dysfunction affects cortical circuits in diseases such as PD, DLB, and AD.
Details
- Title: Subtitle
- Scopolamine and Medial Frontal Stimulus-Processing during Interval Timing
- Creators
- Qiang Zhang - Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States of AmericaDennis Jung - Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States of AmericaTravis Larson - Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States of AmericaYoungcho Kim - Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States of AmericaNandakumar S Narayanan - Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States of America. Electronic address: Nandakumar-narayanan@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.414, pp.219-227
- DOI
- 10.1016/j.neuroscience.2019.07.004
- PMID
- 31299344
- PMCID
- PMC7040457
- NLM abbreviation
- Neuroscience
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Publisher
- United States
- Grant note
- R01 MH116043 / NIMH NIH HHS
- Language
- English
- Date published
- 08/21/2019
- Academic Unit
- Neurology; Iowa Neuroscience Institute
- Record Identifier
- 9984070483102771
Metrics
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