Distinct neural mechanisms mediate olfactory memory formation at different timescales

Abstract

Habituation is one of the oldest forms of learning, broadly expressed across sensory systems and taxa. Here, we demonstrate that olfactory habituation induced at different timescales (comprising different odor exposure and intertrial interval durations) is mediated by different neural mechanisms. First, the persistence of habituation memory is greater when mice are habituated on longer timescales. Second, the specificity of the memory (degree of cross-habituation to similar stimuli) also depends on induction timescale. Third, we demonstrate a pharmacological double dissociation between the glutamatergic mechanisms underlying short-and long-timescale odor habituation. LY341495, a class II/III metabotropic glutamate receptor antagonist, blocked habituation only when the induction timescale was short. Conversely, MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, prevented habituation only when the timescale was long. Finally, whereas short-timescale odor habituation is mediated within the anterior piriform cortex, infusion of MK-801 into the olfactory bulbs prevented odor habituation only at longer timescales. Thus, we demonstrate two neural mechanisms underlying simple olfactory learning, distinguished by their persistence and specificity, mediated by different olfactory structures and pharmacological effectors, and differentially utilized based solely on the timescale of odor presentation.Habituation, or the progressive reduction in behavioral responsiveness to repeated similar stimuli, is a simple form of learning that underlies animals' capacity to perceptually deemphasize static conditions or inconsequential stimuli in favor of novel, potentially more relevant environmental features or events (Thompson and Spencer 1966;Rose and Rankin 2001). In the laboratory, experimental paradigms based on habituation have been employed to study the properties of nonassociative perceptual learning, to measure the persistence of memory traces, and even to assess the stringency of spontaneous discrimination among similar stimuli. In studies of olfactory spontaneous discrimination using rats or mice, animals habituated to an odorant stimulus demonstrate a cross-habituation response to novel odorant stimuli that are structurally and perceptually similar to the habituated odorant. The degree of cross-habituation declines progressively as test odorants become more dissimilar, and habituation to both the original and cross-habituated odorant stimuli persists for at least several minutes (Cleland et al. 2002;Linster et al. 2002; Mandairon et al. 2006b,c).Olfactory habituation has also been observed in studies in which it is attributed to rapid synaptic adaptation of the mitrapyramidal synapse in the rat anterior piriform cortex (aPC) (Best and Wilson 2004;Yadon and Wilson 2005). Odor-evoked activity in piriform pyramidal neurons adapts within tens of seconds, and this adaptation persists for up to 2 min (Wilson 1998a,b), a substantially faster timescale than that exhibited in the behavioral studies discussed above. Further...

Neuronal nitric-oxide synthase deficiency impairs the long-term memory of olfactory fear learning and increases odor generalization

“…1D) and in the glomerular layer of the olfactory bulb (Fig. 1E), which are necessary for olfactory learning (McNamara et al 2008). Knockout mice failed to express the nNOS cells in these areas, which is in accordance with previous studies (Kelley et al 2009).…”

“…On the fourth and fifth trials, other similar and dissimilar odors are presented to measure discriminatory ability. Similar to other studies, control mice displayed significant levels of olfactory habituation, as measured by H3 investigation times, as well as the ability to discriminate both similar and dissimilar odorants (Cleland et al 2002;McNamara et al 2008). Both knockout and wild-type mice with reduced nNOS also displayed similar levels of habituation and discrimination as control mice.…”

“…It has been well documented that animals can habituate to odor stimulus in a short-term memory paradigm (Cleland et al 2002;McNamara et al 2008). Mice were placed in a standard mouse cage with a wooden bead (1 cm diameter; Craftparts) containing a small piece of filter paper saturated with 0.02 mL of E5 dissolved in mineral oil that was placed in the center of the cage.…”

“…To test whether or not decreased NO levels can affect olfactory detection and discrimination, we used a well-established habituation-cross habituation paradigm (Cleland et al 2002;McNamara et al 2008). In this task, mice are presented with a novel odor for three trials to determine the amount of habituation.…”

Group III Metabotropic Glutamate Receptors Inhibit Startle-Mediating Giant Neurons in the Caudal Pontine Reticular Nucleus But Do Not Mediate Synaptic Depression/Short-Term Habituation of Startle

“…It has been shown in odor habituation in rats that different stimulus protocols can activate entirely different mechanisms (McNamara et al, 2008). Although the stimulus presentation time in mGluR-mediated odor habituation is longer than in startle experiments (4 -20 s vs 20 ms), the interstimulus intervals were comparable between the two studies (10 s vs 15 s).…”