title: Distinct roles of bulbar muscarinic and nicotinic receptors in olfactory discrimination learning.
abstract: The olfactory bulb (OB) and piriform cortex receive dense cholinergic projections from the basal forebrain. Cholinergic modulation within the piriform cortex has long been proposed to serve important functions in olfactory learning and memory. We here investigate how olfactory discrimination learning is regulated by cholinergic modulation of the OB inputs to the piriform cortex. We examined rats' performance on a two-alternative choice odor discrimination task following local, bilateral blockade of cholinergic nicotinic and/or muscarinic receptors in the OB. Results demonstrate that acquisition, but not recall, of novel discrimination problems is impaired following blockade of OB cholinergic receptors, although the relative contribution of muscarinic and nicotinic receptors depends on task difficulty. Blocking muscarinic receptors impairs learning for nearly all odor sets, whereas blocking nicotinic receptors only affects performance for perceptually similar odors. This pattern of behavioral effects is consistent with predictions from a model of cholinergic modulation in the OB and piriform cortex (de Almeida et al., 2013). Model simulations suggest that muscarinic and nicotinic receptors may serve complementary roles in regulating coherence and sparseness of the OB network output, which in turn differentially regulate the strength and overlap in cortical odor representations. Overall, our results suggest that muscarinic receptor blockade results in a bona fide learning impairment that may arise because cortical neurons are activated less often. Behavioral impairment following nicotinic receptor blockade may not be due to the inability of the cortex to learn, but rather arises because the cortex is unable to resolve highly overlapping input patterns.
authors.affiliation: Department of Neurobiology and Behavior, Cornell University, Ithaca, New York 14850.
authors.forename: Sasha
authors.initials: S
authors.lastname: Devore
authors.affiliation: Department of Neurobiology and Behavior, Cornell University, Ithaca, New York 14850.
authors.forename: Licurgo
authors.identifier: http://orcid.org/0000-0001-7041-6587
authors.initials: L
authors.lastname: de Almeida
authors.affiliation: Department of Neurobiology and Behavior, Cornell University, Ithaca, New York 14850 cl243@cornell.edu.
authors.forename: Christiane
authors.initials: C
authors.lastname: Linster
mesh_terms: D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology; D003198:Computer Simulation; D003216:Conditioning, Operant; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008954:Models, Biological; D009812:Odorants; D009830:Olfactory Bulb / Q000187:drug effects / Q000502:physiology*; D009833:Olfactory Pathways / Q000187:drug effects / Q000502:physiology*; D066195:Piriform Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D011976:Receptors, Muscarinic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*
chemical_list: D018678:Cholinergic Agents; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic
keywords: acetylcholine; cholinergic neuromodulation; olfactory bulb; olfactory cortex; rodent behavior