title: Cholinergic modulation of the spatiotemporal pattern of hippocampal activity in vitro.
abstract: The aim of this study was to use optical imaging with voltage-sensitive dyes (Di-4-ANEPPS), to examine the cholinergic modulation of CA1 network responses to Schaffer collateral input. By comparing responses recorded with optical imaging and field recordings across the proximodistal axis of CA1, it was initially demonstrated that voltage-sensitive dyes could report reliably both the pattern of activation and cholinergic modulation. The higher spatial resolution of optical imaging was used to explore the somatodendritic profile of cholinergic modulation. It was found that activation of muscarinic acetylcholine receptors (mAChR) (1-10 microM carbachol), inhibited evoked responses across all layers of CA1. This was accompanied by an increase in paired-pulse facilitation in the apical and distal dendritic layers (40 ms inter-stimulus interval), but not in perisomatic regions. The mAChR antagonist, 20 microM atropine, alone increased facilitation at perisomatic sites, suggesting that muscarinic signalling pathways actively suppress perisomatic responses to repetitive stimulation. In contrast, the activation of nicotinic acetylcholine receptors (10 microM nicotine) had no significant effect on single evoked responses, but selectively increased facilitation at perisomatic sites. These results suggest that cholinergic modulation of the hippocampal CA1 network has multiple differential effects on the somatodendritic processing of the Schaffer collateral input.
authors.affiliation: Department of Pharmacology, Oxford University, Mansfield Road, Oxford OX1 3QT, UK. ed.mann@pharm.ox.ac.uk
authors.forename: Edward O
authors.initials: EO
authors.lastname: Mann
authors.forename: Takashi
authors.initials: T
authors.lastname: Tominaga
authors.forename: Michinori
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Susan A
authors.initials: SA
authors.lastname: Greenfield
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D013057:Spectrum Analysis / Q000379:methods; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
chemical_list: D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D001285:Atropine; D002217:Carbachol; D000109:Acetylcholine