title: Cholinergic suppression: a postsynaptic mechanism of long-term associative learning.
abstract: Food avoidance learning in the mollusc Pleurobranchaea entails reduction in the responsiveness of key brain interneurons in the feeding neural circuitry, the paracerebral feeding command interneurons (PCNs), to the neurotransmitter acetylcholine (AcCho). Food stimuli applied to the oral veil of an untrained animal depolarize the PCNs and induce the feeding motor program (FMP). Atropine (a muscarinic cholinergic antagonist) reversibly blocks the food-induced depolarization of the PCNs, implicating AcCho as the neurotransmitter mediating food detection. AcCho applied directly to PCN somata depolarizes them, indicating that the PCN soma membrane contains AcCho receptors and induces the FMP in the isolated central nervous system preparation. The AcCho response of the PCNs is mediated by muscarinic-like receptors, since comparable depolarization is induced by muscarinic agonists (acetyl-beta-methylcholine, oxotremorine, pilocarpine), but not nicotine, and blocked by muscarinic antagonists (atropine, trifluoperazine). The nicotinic antagonist hexamethonium, however, blocked the AcCho response in four of six cases. When specimens are trained to suppress feeding behavior using a conventional food-avoidance learning paradigm (conditionally paired food and shock), AcCho applied to PCNs in the same concentration as in untrained animals causes little or no depolarization and does not initiate the FMP. Increasing the concentration of AcCho 10-100 times, however, induces weak PCN depolarization in trained specimens, indicating that learning diminishes but does not fully abolish AcCho responsiveness of the PCNs. This study proposes a cellular mechanism of long-term associative learning--namely, postsynaptic modulation of neurotransmitter responsiveness in central neurons that could apply also to mammalian species.
authors.forename: A D
authors.initials: AD
authors.lastname: Morielli
authors.forename: E M
authors.initials: EM
authors.lastname: Matera
authors.forename: M P
authors.initials: MP
authors.lastname: Kovac
authors.forename: R G
authors.initials: RG
authors.lastname: Shrum
authors.forename: K J
authors.initials: KJ
authors.lastname: McCormack
authors.forename: W J
authors.initials: WJ
authors.lastname: Davis
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001285:Atropine / Q000494:pharmacology; D001362:Avoidance Learning / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology; D007395:Interneurons / Q000502:physiology; D007858:Learning / Q000502:physiology*; D008974:Mollusca / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology; D013570:Synaptic Membranes / Q000502:physiology
chemical_list: D011976:Receptors, Muscarinic; D001285:Atropine; D000109:Acetylcholine