Plasticity in the olfactory system: lessons for the neurobiology of memory

Abstract

We are rapidly advancing toward an understanding of the molecular events underlying odor transduction, mechanisms of spatiotemporal central odor processing, and neural correlates of olfactory perception and cognition. A thread running through each of these broad components that define olfaction appears to be their dynamic nature. How odors are processed, at both the behavioral and neural level, is heavily dependent on past experience, current environmental context, and internal state. The neural plasticity that allows this dynamic processing is expressed nearly ubiquitously in the olfactory pathway, from olfactory receptor neurons to the higher-order cortex, and includes mechanisms ranging from changes in membrane excitability to changes in synaptic efficacy to neurogenesis and apoptosis. This review will describe recent findings regarding plasticity in the mammalian olfactory system that are believed to have general relevance for understanding the neurobiology of memory.

Figures

Fig. 1

Schematic representation of mammalian olfactory system circuitry. As described in the text, olfactory receptor neurons expressing one of many hundreds of different receptor proteins target single glomeruli in the olfactory bulb where they synapse on mitral cells. Mitral cells receive inhibitory inputs from Juxtaglomerular neurons and granule cells and send their axons to the piriform cortex where they converge with mitral cells conveying input from different receptors. Higher-order connections include other regions of the olfactory cortex and limbic system structures.

Fig. 2

Examples of single-unit responses to odor and to non-odor stimulation in the rat olfactory system. Left, Local field potential (LFP; filtered for β wave activity, 15–45 Hz) and mitral cell single-unit activity in response to a 2-sec odor pulse. Respiration as monitored by chest wall movements is the bottom trace. Note the increase in both firing rate and temporal correlation with the respiratory cycle during the odor stimulus. The firing bursts correspond to β frequency bursts in the LFP. similar responses to odor can be observed in the piriform cortex (not shown). Right, Piriform cortex single-unit response to repeated 200-ms footshock in a urethane anesthetized rat. Rasterplot and cumulative peristimulus histogram show footshock-evoked increase in cortical firing rate, but note that firing is selectively increased in phase with respiration to produce bursts on each inhalation (respiration not shown). This suggests that rather than directly responding to the footshock, the footshock enhances responsiveness to olfactory input (Bouret, Wilson, and Sara, unpublished observations).

Fig. 3

Examples of two mechanisms of short-term synaptic plasticity in the olfactory system. Left, Afferent input to the olfactory bulb can be regulated by dopaminergic feedback to D2 receptors on the olfactory receptor axons. As described in the text, dopamine levels are modulated by odor stimulation such that reduced odor stimulation reduces dopamine expression and releases olfactory nerve axon terminals from presynaptic inhibition. This could produce an activity-dependent regulation of afferent input efficacy. In the piriform cortex (right), mitral cell axon transmitter release is modulated by mGluR autoreceptors. During periods of intense input (e.g., prolonged odor stimulation), transmitter release is reduced, potentially producing cortical odor adaptation.

Fig. 4

Examples of two mechanisms of long-term plasticity in the olfactory system. Left, In the olfactory bulb, mitral cells receive convergent odor and centrifugal inputs such as norepinephrine from the locus coeruleus. When an odor is paired with an arousing (locus coeruleus activating) unconditioned stimulus, the combination can induce an intracellular second messenger cascade activating CREB and modifying gene transcription for long-term changes in cell function. Right, In the piriform cortex, association of odor-evoked association fiber activity with cholinergic input can produce a variety of synaptic and membrane biophysical changes that result in modified pyramidal cell responses to subsequent odor stimulation and heightened probability of further plasticity (see text).

Fig. 5

Examples of olfactory rule/set learning and olfactory perceptual learning behavioral data. Top, After becoming familiar with an odor, that odor becomes more distinct from molecularly similar odors (perceptual learning). Naive rats are unable to discriminate unfamiliar ethyl esters varying by a single carbon, whereas after a familiarization procedure, they are capable of making this discrimination. Blockade of ACh muscarinic receptors with scopolamine during the familiarization training prevents perceptual learning. Bottom, As rats are given repeated discrimination training with new odor pairs (e.g., discriminate apple from banana, then discriminate coffee from mint, etc.), they significantly improve their learning speed, such that often only single trials are required for subsequent errorless performance after a few odor pairs. Data adapted from Slotnick and others (2000).