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

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Muscarinic Receptor-Dependent Long Term Depression in the Perirhinal Cortex and Recognition Memory are Impaired in the rTg4510 Mouse Model of Tauopathy. / Scullion, Sarah E.; Barker, Gareth R.I.; Warburton, E. Clea; Randall, Andrew D.; Brown, Jonathan T.

In: Neurochemical Research, Vol. 44, No. 3, 03.2019, p. 617-626.

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@article{fac6ab8f50d1400999ce8ca2acc7f142,
title = "Muscarinic Receptor-Dependent Long Term Depression in the Perirhinal Cortex and Recognition Memory are Impaired in the rTg4510 Mouse Model of Tauopathy",
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.",
keywords = "Alzheimer’s disease, Fronto-temporal dementia, rTg4510, Synaptic plasticity",
author = "Scullion, {Sarah E.} and Barker, {Gareth R.I.} and Warburton, {E. Clea} and Randall, {Andrew D.} and Brown, {Jonathan T.}",
year = "2019",
month = "3",
doi = "10.1007/s11064-018-2487-x",
language = "English",
volume = "44",
pages = "617--626",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Springer US",
number = "3",

}

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TY - JOUR

T1 - Muscarinic Receptor-Dependent Long Term Depression in the Perirhinal Cortex and Recognition Memory are Impaired in the rTg4510 Mouse Model of Tauopathy

AU - Scullion, Sarah E.

AU - Barker, Gareth R.I.

AU - Warburton, E. Clea

AU - Randall, Andrew D.

AU - Brown, Jonathan T.

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

KW - Alzheimer’s disease

KW - Fronto-temporal dementia

KW - rTg4510

KW - Synaptic plasticity

UR - http://www.scopus.com/inward/record.url?scp=85042525888&partnerID=8YFLogxK

U2 - 10.1007/s11064-018-2487-x

DO - 10.1007/s11064-018-2487-x

M3 - Article

VL - 44

SP - 617

EP - 626

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 3

ER -