Olfaction and Schizophrenia Essay

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Olfactory discrimination varies in mice with different levels of α7-nicotinic acetylcholine receptor expression
Jennifer L. Hellier a,d,⁎, Nicole L. Arevalo a,d , Megan J. Blatner a,d , An K. Dang a,d , Amy C. Clevenger a,c,d , Catherine E. Adams b,e , Diego Restrepo a,c,d a Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA c Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA d Rocky Mountain Taste and Smell Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA e Denver Veterans Administration Medical Center, Denver, CO 80220, USA b A R T I C LE I N FO Article history: Accepted 8 August 2010 Available online 13 August 2010 Keywords: α7-nACh Odor discrimination Olfaction Behavior α-bungarotoxin MLPEST

AB S T R A C T Previous studies have shown that schizophrenics have decreased expression of α7-nicotinic acetylcholine (α7) receptors in the hippocampus and other brain regions, paranoid delusions, disorganized speech, deficits in auditory gating (i.e., inability to inhibit neuronal responses to repetitive auditory stimuli), and difficulties in odor discrimination and detection. Here we use mice with decreased α7 expression that also show a deficit in auditory gating to determine if these mice have similar deficits in olfaction. In the adult mouse olfactory bulb (OB), α7 expression localizes in the glomerular layer; however, the functional role of α7 is unknown. We show that inbred mouse strains (i.e., C3H and C57) with varying α7 expressions (e.g., α7 wild-type [α7+/+], α7 heterozygous knock-out [α7+/−] and α7 homozygous knock-out mice [α7−/−]) significantly differ in odor discrimination and detection of chemically-related odorant pairs. Using [125I] α-bungarotoxin (α-BGT) autoradiography, α7 expression was measured in the OB. As previously demonstrated, α-BGT binding was localized to the glomerular layer. Significantly more expression of α7 was observed in C57 α7+/+ mice compared to C3H α7+/+ mice. Furthermore, C57 α7+/+ mice were able to detect a significantly lower concentration of an odor in a mixture compared to C3H α7+/+ mice. Both C57 and C3H α7+/+ mice discriminated between chemically-related odorants sooner than α7+/− or α7−/− mice. These data suggest that α7-nicotinic-receptors contribute strongly to olfactory discrimination and detection in mice and may be one of the mechanisms producing olfactory dysfunction in schizophrenics. © 2010 Elsevier B.V. All rights reserved.

⁎ Corresponding author. University of Colorado Anschutz Medical Campus, Mail Stop 8108, 12801 East 17th Avenue, Aurora, CO 80045, USA. Fax: +1 303 724 3420. E-mail address: Jennifer.Hellier@ucdenver.edu (J.L. Hellier). Abbreviations: α7, α7-nicotinic acetylcholine receptor; nAChR, nicotinic acetylcholine receptor; +/+, wild type; +/−, heterozygous knockout; −/−, homozygous knock-out; α-BTX, [125I] α-bungarotoxin; OB, olfactory bulb; HDB, horizontal limb of the diagonal band of Broca; PC, piriform cortex; MLPEST, Maximum Likelihood Parameter ESTimation; MO, mineral oil; OSN, olfactory sensory neurons 0006-8993/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2010.08.027

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Introduction

Approximately 0.4–0.6% of the population (Goldner et al., 2002; Bhugra, 2005) is diagnosed with schizophrenia, a psychiatric disease characterized by inaccurate perceptions of reality, commonly manifested by auditory and olfactory hallucinations, paranoid delusions, disorganized speech, and deficits in odor detection, odor discrimination, and learning (Isseroff et al., 1987;

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