Your browser doesn't support javascript.
loading
Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus.
Dennis, Siobhan H; Pasqui, Francesca; Colvin, Ellen M; Sanger, Helen; Mogg, Adrian J; Felder, Christian C; Broad, Lisa M; Fitzjohn, Steve M; Isaac, John T R; Mellor, Jack R.
Afiliación
  • Dennis SH; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK.
  • Pasqui F; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK.
  • Colvin EM; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK.
  • Sanger H; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK.
  • Mogg AJ; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK.
  • Felder CC; Neuroscience, Eli Lilly & Company, Indianapolis, IN 46285, USA.
  • Broad LM; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK.
  • Fitzjohn SM; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK.
  • Isaac JT; Neuroscience, Eli Lilly & Company, Windlesham, Surrey GU20 6PH, UK.
  • Mellor JR; School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK.
Cereb Cortex ; 26(1): 414-26, 2016 Jan.
Article en En | MEDLINE | ID: mdl-26472558
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.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Potenciación a Largo Plazo / Colinérgicos / Receptor Muscarínico M1 / Hipocampo / Plasticidad Neuronal Límite: Animals Idioma: En Revista: Cereb Cortex Asunto de la revista: CEREBRO Año: 2016 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Potenciación a Largo Plazo / Colinérgicos / Receptor Muscarínico M1 / Hipocampo / Plasticidad Neuronal Límite: Animals Idioma: En Revista: Cereb Cortex Asunto de la revista: CEREBRO Año: 2016 Tipo del documento: Article País de afiliación: Reino Unido