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      Is Open Access

      Paying attention to smell: cholinergic signaling in the olfactory bulb

      review-article
      ,
      Frontiers in Synaptic Neuroscience
      Frontiers Media S.A.
      muscarinic, nicotinic, glomerular, GABAergic, filter

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          Abstract

          The tractable, layered architecture of the olfactory bulb (OB), and its function as a relay between odor input and higher cortical processing, makes it an attractive model to study how sensory information is processed at a synaptic and circuit level. The OB is also the recipient of strong neuromodulatory inputs, chief among them being the central cholinergic system. Cholinergic axons from the basal forebrain modulate the activity of various cells and synapses within the OB, particularly the numerous dendrodendritic synapses, resulting in highly variable responses of OB neurons to odor input that is dependent upon the behavioral state of the animal. Behavioral, electrophysiological, anatomical, and computational studies examining the function of muscarinic and nicotinic cholinergic receptors expressed in the OB have provided valuable insights into the role of acetylcholine (ACh) in regulating its function. We here review various studies examining the modulation of OB function by cholinergic fibers and their target receptors, and provide putative models describing the role that cholinergic receptor activation might play in the encoding of odor information.

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          Most cited references91

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          The cholinergic hypothesis of geriatric memory dysfunction.

          Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed. An attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature. Significant cholinergic dysfunctions occur in the aged and demented central nervous system, relationships between these changes and loss of memory exist, similar memory deficits can be artificially induced by blocking cholinergic mechanisms in young subjects, and under certain tightly controlled conditions reliable memory improvements in aged subjects can be achieved after cholinergic stimulation. Conventional attempts to reduce memory impairments in clinical trials hav not been therapeutically successful, however. Possible explanations for these disappointments are given and directions for future laboratory and clinical studies are suggested.
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            Prefrontal acetylcholine release controls cue detection on multiple timescales.

            Cholinergic neurons originating from the basal forebrain innervate the entire cortical mantle. Choline-sensitive microelectrodes were used to measure the synaptic release of cortical acetylcholine (ACh) at a subsecond resolution in rats performing a task involving the detection of cues. Cues that were detected, defined behaviorally, evoked transient increases in cholinergic activity (at the scale of seconds) in the medial prefrontal cortex (mPFC), but not in a nonassociational control region (motor cortex). In trials involving missed cues, cholinergic transients were not observed. Cholinergic deafferentation of the mPFC, but not motor cortex, impaired cue detection. Furthermore, decreases and increases in precue cholinergic activity predicted subsequent cue detection or misses, respectively. Finally, cue-evoked cholinergic transients were superimposed over slower (at the timescale of minutes) changes in cholinergic activity. Cortical cholinergic neurotransmission is regulated on multiple timescales to mediate the detection of behaviorally significant cues and to support cognitive performance.
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              Topographic organization of sensory projections to the olfactory bulb.

              The detection of odorant receptor mRNAs within the axon terminals of sensory neurons has permitted us to ask whether neurons expressing a given receptor project their axons to common glomeruli within the olfactory bulb. In situ hybridization with five different receptor probes demonstrates that axons from neurons expressing a given receptor converge on one, or at most, a few glomeruli within the olfactory bulb. Moreover, the position of specific glomeruli is bilaterally symmetric and is constant in different individuals within a species. These data support a model in which exposure to a given odorant may result in the stimulation of a spatially restricted set of glomeruli, such that the individual odorants would be associated with specific topographic patterns of activity within the olfactory bulb.
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                Author and article information

                Contributors
                Journal
                Front Synaptic Neurosci
                Front Synaptic Neurosci
                Front. Synaptic Neurosci.
                Frontiers in Synaptic Neuroscience
                Frontiers Media S.A.
                1663-3563
                25 September 2014
                2014
                : 6
                : 21
                Affiliations
                Department of Physiology and Biophysics and the Neuroscience Program, School of Medicine, University of Colorado Aurora, CO, USA
                Author notes

                Edited by: Darwin K. Berg, University of California, San Diego, USA

                Reviewed by: Joseph F. Margiotta, University of Toledo College of Medicine, USA; Jie Wu, Barrow Neurological Institute, USA

                *Correspondence: Sukumar Vijayaraghavan, Department of Physiology and Biophysics and the Neuroscience Program, School of Medicine, University of Colorado, MS 8307, P18-7121, 12800 East 19th Avenue, Aurora, CO 80045, USA e-mail: sukumar.v@ 123456ucdenver.edu

                Present address: Rinaldo D. D’Souza, Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA

                This article was submitted to the journal Frontiers in Synaptic Neuroscience.

                Article
                10.3389/fnsyn.2014.00021
                4174753
                25309421
                23478bef-6e39-41f0-927d-f08b2485cb1f
                Copyright © 2014 D’Souza and Vijayaraghavan.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 June 2014
                : 05 September 2014
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 111, Pages: 11, Words: 0
                Categories
                Neuroscience
                Review Article

                Neurosciences
                muscarinic,nicotinic,glomerular,gabaergic,filter
                Neurosciences
                muscarinic, nicotinic, glomerular, gabaergic, filter

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