Perceptual learning is required for olfactory function to adapt appropriately to changing odor environments. We here show that newborn neurons in the olfactory bulb are not only involved in, but necessary for, olfactory perceptual learning. First, the discrimination of perceptually similar odorants improves in mice after repeated exposure to the odorants. Second, this improved discrimination is accompanied by an elevated survival rate of newborn inhibitory neurons, preferentially involved in processing of the learned odor, within the olfactory bulb. Finally, blocking neurogenesis before and during the odorant exposure period prevents this learned improvement in discrimination. Olfactory perceptual learning is thus mediated by the reinforcement of functional inhibition in the olfactory bulb by adult neurogenesis. discrimination ͉ mice ͉ enrichment ͉ olfactory bulb P erceptual learning is an implicit (nonassociative) form of learning in which discrimination between sensory stimuli is improved by previous experience (1). For instance, animals trained on a tactile discrimination task improve their behavioral performances and in parallel, the neural representation of the stimuli is sharpened (2, 3). In the olfactory modality, perceptual learning has been shown to occur in humans (4), and an experimental model of olfactory perceptual learning has recently been proposed in rats (5). Olfactory perceptual learning is crucial for basic olfactory functions because it sets the degree of discrimination between stimuli, and thus contributes to the perceptual representation of the environment, which guides the animal's behavior. However, neural mechanisms underlying such changes of perception remain elusive. We here show that a modulation of newborn cell survival in the olfactory bulb (OB) underlies olfactory perceptual learning. We show that neurogenesis is not only involved in, but necessary for perceptual learning to occur.We have shown that odor enrichment enhances rats' ability to discriminate between chemically similar odorants in a relatively odor-unspecific manner (5, 6). Indeed, the discrimination of a pair of similar odorants is improved by enrichment with the same odorants or with other odorants that activate regions of the OB partially overlapping with the regions activated by the discriminated pair. Even if the mechanisms underlying this learning remain unclear, it has been shown that infusions of NMDA into the OB improves odor discrimination in a manner similar to odor enrichment indicating that changes in OB processing contribute at least partially to the perceptual plasticity (5). A computational model proposed that activation of OB neurons produces widespread changes in inhibitory processing, which can underlie the observed improvement of odor discrimination (5). In support to this model, odor exposure has been shown to increase inhibition of mitral cells (7) and to increase the responsiveness of the inhibitory granule cells to odorants, as measured by expression of an immediate early gene (8).Inhibitory neuro...

Experimental and modeling data suggest that the circuitry of the main olfactory bulb (OB) plays a critical role in olfactory discrimination. Processing of such information arises from the interaction between OB output neurons local interneurons, as well as interactions between the OB network and centrifugal inputs. Cholinergic input to the OB in particular has been hypothesized to regulate mitral cell odorants receptive fields (ORFs) and behavioral discrimination of similar odorants. We recorded from individual mitral cells in the OB in anesthetized rats to determine the degree of overlap in ORFs of individual mitral cells after exposure to odorant stimuli. Increasing the efficacy of the cholinergic neurotransmission in the OB by addition of the anticholinesterase drug neostigmine (20 mM) sharpened the ORF responses of mitral cells. Furthermore, coaddition of either the nicotinic antagonist methyllycaconitine citrate hydrate (MLA) (20 mM) or muscarinic antagonist scopolamine (40 mM) together with neostigmine (20 mM) attenuated the neostigmine-dependent sharpening of ORFs. These electrophysiological findings are predictive of accompanying behavioral experiments in which cholinergic modulation was manipulated by direct infusion of neostigmine, MLA, and scopolamine into the OB during olfactory behavioral tasks. Increasing the efficacy of cholinergic action in the OB increased perceptual discrimination of odorants in these experiments, whereas blockade of nicotinic or muscarinic receptors decreased perceptual discrimination. These experiments show that behavioral discrimination is modulated in a manner predicted by the changes in mitral cell ORFs by cholinergic drugs. These results together present a first direct comparison between neural and perceptual effects of a bulbar neuromodulator.

The mammalian main olfactory bulb (MOB) receives a significant noradrenergic input from the locus coeruleus. Norepinephrine (NE) is involved in the acquisition of conditioned odor preferences in neonatal animals and in some species-specific odor-dependent behaviors. Thus far, the role of NE in odor processing in adult rats remains less studied. We investigated the role of noradrenergic modulation in the MOB on odor detection and discrimination thresholds using behavioral and computational modeling approaches. Adult rats received bilateral MOB injections of vehicle, NE (0.1-1000 microM), noradrenergic receptor antagonists and NE + receptor antagonists combined. NE infusion improved odor detection and discrimination as a function of NE and odor concentration. The effect of NE on detection and discrimination magnitude at any given odor concentration varied in a non-linear function with respect to NE concentration. Receptor antagonist infusion demonstrated that alpha1 receptor activation is necessary for the modulatory effect of NE. Computational modeling showed that increases in the strength of alpha1 receptor activation leads to improved odor signal-to-noise ratio and spike synchronization in mitral cells that may underlie the behaviorally observed decrease of detection and discrimination thresholds. Our results are the first to show that direct infusion of NE or noradrenergic receptor antagonists into a primary sensory network modulates sensory detection and discrimination thresholds at very low stimulus concentrations.

Habituation is a simple form of memory, yet its neurobiological mechanisms are only beginning to be understood in mammals. In the olfactory system, the neural correlates of habituation at a fast experimental timescale involving very short intertrial intervals (tens of seconds) have been shown to depend on synaptic adaptation in olfactory cortex. In contrast, behavioral habituation to odorants on a longer timescale with intertrial intervals of several minutes depends on processes in the olfactory bulb, as demonstrated by pharmacological studies. We here show that behavioral habituation to odorants on this longer timescale has a neuronal activity correlate in the olfactory bulb. Spiking responses of mitral cells in the rat olfactory bulb adapt to, and recover from, repeated odorant stimulation with five-minute intertrial intervals with a timecourse similar to that of behavioral habituation. Moreover, both the behavioral and neuronal effects of odor habituation require functioning NMDA receptors in the olfactory bulb.

Flavor is produced by the integration of taste, olfaction, texture, and temperature, currently thought to occur in the cortex. However, previous work has shown that brainstem taste-related nuclei also respond to multisensory inputs. Here, we test the hypothesis that taste and olfaction interact in the nucleus of the solitary tract (NTS; the first neural relay in the central gustatory pathway) in awake, freely licking rats. Electrophysiological recordings of taste and taste ϩ odor responses were conducted in an experimental chamber following surgical electrode implantation and recovery. Tastants (0.1 M NaCl, 0.1 M sucrose, 0.01 M citric acid, and 0.0001 M quinine) were delivered for five consecutive licks interspersed with five licks of artificial saliva rinse delivered on a VR5 schedule. Odorants were n-amyl acetate (banana), acetic acid (vinegar), octanoic acid (rancid), and phenylethyl alcohol (floral). For each cell, metric space analyses were used to quantify the information conveyed by spike count, by the rate envelope, and by individual spike timing. Results revealed diverse effects of odorants on taste-response magnitude and latency across cells. Importantly, NTS cells were more competent at discriminating taste ϩ odor stimuli versus tastants presented alone for all taste qualities using both rate and temporal coding. The strong interaction of odorants and tastants at the NTS underscores its role as the initial node in the neural circuit that controls food identification and ingestion.