Olfactory discrimination varies in mice with different levels of α7-nicotinic acetylcholine receptor expression.
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 [(125)I] 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.
Hellier
Jennifer L
JL
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Jennifer.Hellier@ucdenver.edu
Arevalo
Nicole L
NL
Blatner
Megan J
MJ
Dang
An K
AK
Clevenger
Amy C
AC
Adams
Catherine E
CE
Restrepo
Diego
D
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects; D002038:Bungarotoxins / Q000493:pharmacokinetics; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology*; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009812:Odorants; D009833:Olfactory Pathways / Q000187:drug effects / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects; D011877:Radionuclide Imaging; D011930:Reaction Time / Q000235:genetics; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012903:Smell / Q000235:genetics / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579166:Chrna7 protein, mouse; D007456:Iodine Isotopes; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor