Muscarinic Receptor-Dependent Long Term Depression in the Perirhinal Cortex and Recognition Memory are Impaired in the rTg4510 Mouse Model of Tauopathy

Sarah E. Scullion, Gareth R.I. Barker, E. Clea Warburton, Andrew D. Randall*, Jonathan T. Brown

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

2 Citations (Scopus)
170 Downloads (Pure)

Abstract

Neurodegenerative diseases affecting cognitive dysfunction, such as Alzheimer’s disease and fronto-temporal dementia, are often associated impairments in the visual recognition memory system. Recent evidence suggests that synaptic plasticity, in particular long term depression (LTD), in the perirhinal cortex (PRh) is a critical cellular mechanism underlying recognition memory. In this study, we have examined novel object recognition and PRh LTD in rTg4510 mice, which transgenically overexpress tauP301L. We found that 8–9 month old rTg4510 mice had significant deficits in long- but not short-term novel object recognition memory. Furthermore, we also established that PRh slices prepared from rTg4510 mice, unlike those prepared from wildtype littermates, could not support a muscarinic acetylcholine receptor-dependent form of LTD, induced by a 5 Hz stimulation protocol. In contrast, bath application of the muscarinic agonist carbachol induced a form of chemical LTD in both WT and rTg4510 slices. Finally, when rTg4510 slices were preincubated with the acetylcholinesterase inhibitor donepezil, the 5 Hz stimulation protocol was capable of inducing significant levels of LTD. These data suggest that dysfunctional cholinergic innervation of the PRh of rTg4510 mice, results in deficits in synaptic LTD which may contribute to aberrant recognition memory in this rodent model of tauopathy.

Original languageEnglish
Pages (from-to)617-626
Number of pages10
JournalNeurochemical Research
Volume44
Issue number3
Early online date26 Feb 2018
DOIs
Publication statusPublished - Mar 2019

Keywords

  • Alzheimer’s disease
  • Fronto-temporal dementia
  • rTg4510
  • Synaptic plasticity

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