title: Endogenous acetylcholine enhances synchronized interneuron activity in rat neocortex.
abstract: Application of 4-aminopyridine (4-AP) along with EAA) receptor antagonists produces gamma-aminobutyric acid (GABAA) receptor-dependent synchronized activity in interneurons. This results in waves of activity propagating through upper cortical layers. Because interneurons in the neocortex are excited by nicotinic acetylcholine receptor (nAChR) agonists, ACh may influence synchronization of these local neocortical interneuronal networks. To study this possibility, we have used voltage-sensitive dye imaging using the fluorescent dye RH 414 (30 microM) in rat neocortical slices. Recordings were obtained in the presence of 4-AP (100 microM) and the EAA receptor antagonists D-2-amino-5-phosphonvaleric acid (20 microM) and 6-cyano-7-nitro-quinoxaline-2,3-dione (10 microM). In response to intracortical stimulation, localized or propagated activity restricted to upper cortical layers was seen. Bath application of the ACh esterase inhibitor neostigmine (10 microM) and the nAChR agonist 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP; 10 microM) increased the response amplitude, the extent of spread, and the duration of this activity. These changes were seen in 13 of 16 slices tested with neostigmine (10 microM) and 4 of 7 slices tested with DMPP (10 microM). Application of the muscarinic AChR antagonist atropine (1 microM) did not block the enhancement of activity by neostigmine (n = 7). Application of dihydro-beta-erythroidine (10 microM), known, at this concentration, to selectively antagonize alpha4beta2-like nAChRs, blocked the effect of neostigmine (n = 5). The selective alpha7-like nAChR antagonist methyllycaconitine (50 nM) was ineffective (n = 5). These results suggest that activation of alpha4beta2-like nAChRs by endogenously released ACh can enhance synchronized activity in local neocortical inhibitory networks.
authors.affiliation: Dept. of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Susanta
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Bernd
authors.initials: B
authors.lastname: Sutor
authors.forename: John J
authors.initials: JJ
authors.lastname: Hablitz
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000502:physiology*; D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D007395:Interneurons / Q000502:physiology*; D019579:Neocortex / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; D011978:Receptors, Nicotinic; D000109:Acetylcholine