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Abstract
Muscarinic M1 acetylcholine receptors (M1Rs) are highly expressed in the hippocampus, and their inhibition or ablation disrupts the encoding of spatial memory. It has been hypothesized that the principal mechanism by which M1Rs influence spatial memory is by the regulation of hippocampal synaptic plasticity. Here, we use a combination of recently developed, well characterized, selective M1R agonists and M1R knock-out mice to define the roles of M1Rs in the regulation of hippocampal neuronal and synaptic function. We confirm that M1R activation increases input resistance and depolarizes hippocampal CA1 pyramidal neurons and show that this profoundly increases excitatory postsynaptic potential-spike coupling. Consistent with a critical role for M1Rs in synaptic plasticity, we now show that M1R activation produces a robust potentiation of glutamatergic synaptic transmission onto CA1 pyramidal neurons that has all the hallmarks of long-term potentiation (LTP): The potentiation requires NMDA receptor activity and bi-directionally occludes with synaptically induced LTP. Thus, we describe synergistic mechanisms by which acetylcholine acting through M1Rs excites CA1 pyramidal neurons and induces LTP, to profoundly increase activation of CA1 pyramidal neurons. These features are predicted to make a major contribution to the pro-cognitive effects of cholinergic transmission in rodents and humans.
Original language | English |
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Pages (from-to) | 414-426 |
Number of pages | 13 |
Journal | Cerebral Cortex |
Volume | 26 |
Issue number | 1 |
Early online date | 14 Sept 2015 |
DOIs | |
Publication status | Published - Jan 2016 |
Keywords
- CA1
- hippocampus
- long-term potentiation
- muscarinic m1 receptor
- synaptic plasticity
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Dive into the research topics of 'Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus'. Together they form a unique fingerprint.Projects
- 1 Finished
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Regulation of spine Ca2+ dynamics and spike timing-dependent synaptic plasticity by muscarinic acetylcholine receptors
Mellor, J. R. (Principal Investigator)
1/10/12 → 1/10/15
Project: Research
Profiles
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Professor Jack R Mellor
- School of Physiology, Pharmacology & Neuroscience - Professor in Neuroscience
- Bristol Neuroscience
Person: Academic , Member