Visualization using the immediate early gene Arc revealed sparser and more robust odor representations in the anterior piriform cortex of adult rats when odor was associated with water reward over 2-3 d. Rewarded odor "mixtures" resulted in rats responding to either component odor similarly, and, correspondingly, the odor representations became more similar as indexed by increased overlap in piriform Arc-expressing (Arc ϩ ) pyramidal neurons. The increased overlap was consistent with the rats' generalization from component odors. Discriminating among highly similar odor mixtures for reward led to increased differentiation of the neural representations as indexed by a reduction in overlap for piriform Arc ϩ pyramidal neurons after training. Similar odor mixture discrimination also required more trials to criterion. The visible reduction in the overlap of odor representations indexes pattern separation. The Arc visualization of odor representations in the anterior piriform network suggests that odor objects are widely distributed representations and can be rapidly modified by reward training in adult rats. We suggest that dynamic changes such as those observed here in piriform odor encoding are at the heart of perceptual learning and reflect the continuing plastic nature of mature associative cortex as an outcome of successful problem solving.

Arc ensembles in adult rat olfactory bulb (OB) and anterior piriform cortex (PC) were assessed after discrimination training on highly similar odor pairs. Nonselective ␣-and ␤-adrenergic antagonists or saline were infused in the OB or anterior PC during training. OB adrenergic blockade slowed, but did not prevent, odor discrimination learning. After criterion performance, Arc ensembles in anterior piriform showed enhanced stability for the rewarded odor and pattern separation for the discriminated odors as described previously. Anterior piriform adrenergic blockade prevented acquisition of similar odor discrimination and of OB ensemble changes, even with extended overtraining. Mitral and granule cell Arc ensembles in OB showed enhanced stability for rewarded odor only in the saline group. Pattern separation was not seen in the OB. Similar odor discrimination co-occurs with increased stability in rewarded odor representations and pattern separation to reduce encoding overlap. The difficulty of similar discriminations may relate to the necessity to both strengthen rewarded representations and weaken overlap across similar representations.

The nature of memory is a central issue in neuroscience. How does our representation of the world change with learning and experience? Here we use the transcription of Arc mRNA, which permits probing the neural representations of temporally separated events, to address this in a well characterized odor learning model. Rat pups readily associate odor with maternal care. In pups, the lateralized olfactory networks are independent, permitting separate training and within-subject control. We use multiday training to create an enduring memory of peppermint odor. Training stabilized rewarded, but not nonrewarded, odor representations in both mitral cells and associated granule cells of the olfactory bulb and in the pyramidal cells of the anterior piriform cortex. An enlarged core of stable, likely highly active neurons represent rewarded odor at both stages of the olfactory network.Odor representations in anterior piriform cortex were sparser than typical in adult rat and did not enlarge with learning. This sparser representation of odor is congruent with the maturation of lateral olfactory tract input in rat pups. Cortical representations elsewhere have been shown to be highly variable in electrophysiological experiments, suggesting brains operate normally using dynamic and network-modulated representations. The olfactory cortical representations here are consistent with the generalized associative model of sparse variable cortical representation, as normal responses to repeated odors were highly variable (ϳ70% of the cells change as indexed by Arc). Learning and memory modified rewarded odor ensembles to increase stability in a core representational component.

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In this study, three lines of evidence suggest a role for a 2 -adrenoreceptors in rat pup odor-preference learning: olfactory bulb infusions of the a 2 -antagonist, yohimbine, prevents learning; the a 2 -agonist, clonidine, paired with odor, induces learning; and subthreshold clonidine paired with subthreshold b-adrenoceptor activation also recruits learning. Increased mitral cell layer pCREB occurs with clonidine-infusion, but cAMP is not increased. Similar results using a GABAa-antagonist suggest that disinhibition may support clonidine-induced learning. We suggest that norepinephrine can act through multiple bulbar adrenoceptor subtypes to induce odor learning and that cAMP-dependent, as well as cAMP-independent, signals may act as unconditioned stimuli.Odor-preference learning in the week-old rat pup occurs when a novel odor (conditioned stimulus, CS) is paired with activation of the noradrenergic locus coeruleus. The locus coeruleus is activated by the range of stimuli that can induce odor-preference learning including stroking (Sullivan and Leon 1986;McLean et al. 1993) and feeding (Johanson and Teicher 1980;Kucharski and Hall 1987;Sullivan and Hall 1988), all of which serve as unconditioned stimuli (US). Even rough maternal handling mimicked by mild shocks will engage odor-preference learning (Camp and Rudy 1988;Sullivan et al. 2000a). Odor-preference learning enables rat pups to locate the dam at a period when visual and auditory input is minimal. Odor paired with the activation of b-adrenoceptors in the olfactory bulb is sufficient to induce odor learning, while a bulbar b-adrenoceptor antagonist prevents odorpreference learning (Sullivan et al. 2000b). Thus, the olfactory bulb appears to be the critical site for the CS-US pairing, and the likely location of the odor memory.However, in addition to b-adrenoceptors, which induce odor learning via activation of the cAMP/PKA/CREB cascade (McLean et al. 1999; Yuan et al. 2003a,b;Cui et al. 2007;Grimes et al. 2012), there are bulbar a-adrenoceptors likely to be engaged by norepinephrine (NE) release. Recently, studies of a 2 -adrenoceptor activation in the olfactory bulb in vitro have revealed receptor effects that could promote odor learning (Nai et al. 2010;Pandipati et al. 2010). In particular, the a 2 -adrenoceptor agonist, clonidine, has been shown to decrease granule cell excitability (Nai et al. 2010), releasing the odor-encoding mitral cells from tonic inhibition, and to promote olfactory bulb synchrony at g EEG frequencies (Pandipati et al. 2010). These studies predict a role for a 2 -adrenoceptor activation in odor-preference learning.The present experiments assess the role of bulbar a 2 -adrenoceptors in rat pup odor-preference learning.In all experiments, drugs were infused into the olfactory bulbs on postnatal day (PND) 6. Day of birth was considered PND 0. Sprague-Dawley rat pups of both sexes were used and litters were culled to 12 pups on PND 1. Dams were maintained under a 12-h reverse light/dark cycle at 22˚C in polycarbonate cages with ad l...