Mice with a “Monoclonal Nose”: Perturbations in an Olfactory Map Impair Odor Discrimination

Abstract

SUMMARY The recognition of odors is accomplished in the sensory epithelium where individual olfactory neurons express only one of 1,300 odorant receptor genes. Neurons expressing a given receptor project to two spatially invariant glomeruli in the olfactory bulb such that each odor elicits a distinct and sparse pattern of glomerular activity. We have altered the neural representation of odors in the brain by generating a mouse with a “monoclonal nose” in which greater than 95% of the sensory neurons express a single odorant receptor, M71. As a consequence, the frequency of sensory neurons expressing endogenous receptor genes is reduced twenty-fold. We observe that these mice can smell but odor discrimination and performance in associative olfactory learning tasks are impaired. However, these mice cannot detect the M71 ligand acetophenone despite the observation that virtually all sensory neurons and glomeruli are activated by this odor. The M71 transgenic mice readily detect other odors in the presence of acetophenone. These observations have implications for how receptor activation in the periphery is represented in the brain and how these representations encode odors.

Odorant receptors regulate the final glomerular coalescence of olfactory sensory neuron axons

“…We and others have used the OMP promoter to force the expression of OR genes (19)(20)(21)(22)(23)(24) as well as to knock out genes via Cre-recombinase (25)(26)(27). However, our current results show that OMP is expressed, at the earliest, 48 h after OR expression is initiated and after axons have reached the OB and drawn proximal to the point of glomerular convergence.…”

Cyclic-nucleotide–gated cation current and Ca2+-activated Cl current elicited by odorant in vertebrate olfactory receptor neurons

“…expressing only the M71-OR is surprisingly incapable of detecting behaviorally this specific OR's cognate ligand, acetophenone (66). The bottom line is that the behavior/performance of neuronal circuitry is not necessarily readily predictable.…”

Perceptual convergence of multi-component mixtures in olfaction implies an olfactory white

“…From the visual and auditory neural perspective, "white "typically implies wide activation. Paradoxically, studies that either overexpressed a particular olfactory receptor subtype (32) or used electrical stimulation of the olfactory system (33) together implied that wide olfactory activation results in no percept at all. Thus, it is unlikely that our white was the result of activating the entire sensory apparatus at any level.…”