title: Effects of Selective M1Muscarinic Receptor Activation on Hippocampal Spatial Representations and Neuronal Oscillations.
abstract: The muscarinic M1acetylcholine receptor is a key target for drugs aimed at treating cognitive dysfunction, including the memory impairment in Alzheimer's disease. The overall question of the current study was to ask how systemic administration of the bitopic M1agonist VU0364572, the M1positive allosteric modulator BQCA, and the acetylcholinesterase inhibitor donepezil (current standard of care for Alzheimer's disease), would impact spatial memory-related hippocampal function in rats. Hippocampal pyramidal neuron spiking and local field potentials were recorded from regions CA1 and CA3 as rats freely foraged in a recording enclosure. To assess the relative stability versus flexibility of the rats' spatial representations, the walls of the recording enclosure were reshaped in 15-m intervals. As compared to the control condition, systemic administration of VU0364572 increased spatial correlations of CA1 and CA3 pyramidal neuron spiking across all enclosure shape comparisons, whereas BQCA and donepezil appeared to decrease these spatial correlations. Further, both VU0364572 and BQCA increased intrahippocampal synchrony as measured by CA3-CA1 field-field coherence in frequency ranges that tended to align with the prominence of those oscillations for the behavioral state (i.e., theta during locomotion and slow gamma during stationary moments). The results indicated that VU0364572 and BQCA influenced hippocampal function differently but in ways that might both be beneficial for treating memory dysfunction.
authors.affiliation: Neuroscience Graduate Program, ‡Department of Psychology, §Neuroscience and Behavioral Biology Program, and ∥Department of Neurology, Emory University , Atlanta, Georgia, 30322, United States.
authors.forename: Evan P
authors.initials: EP
authors.lastname: Lebois
authors.affiliation: Neuroscience Graduate Program, ‡Department of Psychology, §Neuroscience and Behavioral Biology Program, and ∥Department of Neurology, Emory University , Atlanta, Georgia, 30322, United States.
authors.forename: John B
authors.initials: JB
authors.lastname: Trimper
authors.affiliation: Neuroscience Graduate Program, ‡Department of Psychology, §Neuroscience and Behavioral Biology Program, and ∥Department of Neurology, Emory University , Atlanta, Georgia, 30322, United States.
authors.forename: Chun
authors.initials: C
authors.lastname: Hu
authors.affiliation: Neuroscience Graduate Program, ‡Department of Psychology, §Neuroscience and Behavioral Biology Program, and ∥Department of Neurology, Emory University , Atlanta, Georgia, 30322, United States.
authors.forename: Allan I
authors.initials: AI
authors.lastname: Levey
authors.affiliation: Neuroscience Graduate Program, ‡Department of Psychology, §Neuroscience and Behavioral Biology Program, and ∥Department of Neurology, Emory University , Atlanta, Georgia, 30322, United States.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Manns
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D000077265:Donepezil; D004567:Electrodes, Implanted; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D007189:Indans / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010507:Periodicity; D010880:Piperidines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D011916:Rats, Inbred F344; D043643:Receptor, Muscarinic M1 / Q000819:agonists / Q000378:metabolism*; D013028:Space Perception / Q000187:drug effects* / Q000502:physiology; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D013826:Theta Rhythm / Q000187:drug effects / Q000502:physiology
chemical_list: C583161:1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; D001549:Benzamides; D001713:Biphenyl Compounds; D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D011804:Quinolines; D043643:Receptor, Muscarinic M1; C574617:VU0364572; D000077265:Donepezil
keywords: Muscarinic; acetylcholine; hippocampus; memory; oscillations; place cell