The central nervous system rapidly learns that particular stimuli predict imminent danger. This learning is thought to involve associations between neutral and harmful stimuli in cortical and limbic brain regions, though associative neuroplasticity in sensory structures is increasingly appreciated. We observed the synaptic output of olfactory sensory neurons (OSNs) in individual mice before and after they learned that a particular odor indicated an impending footshock. OSNs are the first cells in the olfactory system, physically contacting the odor molecules in the nose and projecting their axons to the brain’s olfactory bulb. Surprisingly, OSN output evoked by the shock-predictive odor was selectively facilitated after fear conditioning. These results indicate that affective information about stimuli can be encoded in their very earliest representations in the nervous system.
Long-term plasticity in sensory systems is usually conceptualized as changing the interpretation of the brain of sensory information, not an alteration of how the sensor itself responds to external stimuli. However, here we demonstrate that, in the adult mouse olfactory system, a 1-week-long exposure to an artificially odorized environment narrows the range of odorants that can induce neurotransmitter release from olfactory sensory neurons (OSNs) and reduces the total transmitter release from responsive neurons. In animals heterozygous for the olfactory marker protein (OMP), this adaptive plasticity was strongest in the populations of OSNs that originally responded to the exposure odorant (an ester) and also observed in the responses to a similar odorant (another ester) but had no effect on the responses to odorants dissimilar to the exposure odorant (a ketone and an aldehyde). In contrast, in OMP knock-out mice, odorant exposure reduced the number and amplitude of OSN responses evoked by all four types of odorants equally. The effect of this plasticity is to preferentially sparsen the primary neural representations of common olfactory stimuli, which has the computational benefit of increasing the number of distinct sensory patterns that could be represented in the circuit and might thus underlie the improvements in olfactory discrimination often observed after odorant exposure (Mandairon et al., 2006a). The absence of odorant specificity in this adaptive plasticity in OMP knock-out mice suggests a potential role for this protein in adaptively reshaping OSN responses to function in different environments.
Intranasal exposure to the heavy metal cadmium has been linked to olfactory dysfunction and neurotoxicity. Here, we combine optical imaging of in vivo neurophysiology, genetically defined anatomical tract tracing, mass spectrometry, and behavioral psychophysical methods to evaluate the persistent harmful effects of acute intranasal exposure to cadmium in a mouse model and to investigate the functional consequences of sensory rehabilitation training. We find that an acute intranasal instillation of cadmium chloride leads to an accumulation of cadmium in the brain's olfactory bulb that persists for at least 4 weeks. This is accompanied by persistent severe pathophysiology of the olfactory nerve, a gradual reduction in axonal projections from the olfactory epithelium, and complete impairment on an olfactory detection task. Remarkably, 2 weeks of odorant-guided operant conditioning training proved sufficient to restore olfactory detection performance to control levels in cadmium-exposed mice. Optical imaging from rehabilitated mice showed that this training did not cause any detectable restoration of olfactory nerve function, suggesting that the recovery of function was mediated by central neuroplasticity in which the brain learned to interpret the degraded sensory input. These data demonstrate that sensory learning can mask even severe damage from neurotoxicants and suggest that explicit sensory training may be useful in rehabilitation of olfactory dysfunction.
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