Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats

Metabotropic glutamate receptor 5 (mGlu5) has been implicated in a variety of learning processes and is important for inhibitory avoidance and conditioned taste aversion learning. MGlu5 receptors are physically connected with NMDA receptors and they interact with, and modulate, the function of one another in several brain regions. The present studies used systemic co-administration of an mGlu5 receptor positive allosteric modulator, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and an NMDA receptor antagonist dizocilpine maleate (MK-801) to characterize the interactions of these receptors in two aversive learning tasks. Male Sprague-Dawley rats were trained in a single-trial step-down inhibitory avoidance or conditioned taste aversion task. CDPPB (3 or 10mg/kg, s.c.), delivered by itself prior to the conditioning trial, did not have any effect on performance in either task 48 h after training. However, CDPPB (at 3mg/kg) attenuated the MK-801 (0.2mg/kg, i.p.) induced learning deficit in both tasks. CDPPB also reduced MK-801-induced hyperactivity. These results underlie the importance of mGlu5 and NMDA receptor interactions in modulating memory processing, and are consistent with findings showing the efficacy of positive allosteric modulators of mGlu5 receptors in reversing the negative effects of NMDA receptor antagonists on other behaviors such as stereotypy, sensorimotor gating, or working, spatial and recognition memory.     

Latent inhibition disruption by MK-801 in a conditioned taste-aversion paradigm

N-Methyl-D-aspartate (NMDA) receptors appear to be involved in CS processing and memory consolidation. The present paper analyzed the effect of the non-competitive NMDA receptor antagonist Dizocilpine maleate (MK-801) on Latent Inhibition (LI)-retarded learning of a CS-US association after to-be-CS preexposures at time of testing, using Wistar rats as experimental subjects. If NMDA receptors are involved in CS processing, MK-801 administration should affect LI. In fact, previous experiments revealed that a 2.0mg/kg MK-801 dose, administered 20 h before preexposure and conditioning, abolished LI in a conditioned taste-aversion paradigm. In the present paper, MK-801 (0.2 mg/kg) was either injected after preexposure, after conditioning, or after both preexposure and conditioning stages. LI was abolished when MK-801 was injected after preexposure, but not when it was injected after conditioning. These results support the role of NMDA receptors in CS processing and memory consolidation.     

Memory-Enhancing Treatments Do Not Reverse the Impairment of Inhibitory Avoidance Retention Induced by NMDA Receptor Blockade

The aim of the present research was to verify whether the impairment of retention induced by the N-methyl-d-aspartate (NMDA) receptor blocker (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cycloheptene-5,10 imine (MK-801) can be reversed by memory-enhancing treatments. Adult female Wistar rats were trained and tested in a step-down inhibitory avoidance task (0.3-mA foot shock, 24-h training-test interval). Animals were given an ip injection of saline (SAL) or MK-801 (0.0625 mg/kg) 30 minutes before training, and an ip injection of SAL, epinephrine (EPI) (25 microg/kg), the opioid receptor antagonist naloxone (NAL) (0.4 mg/kg), the glucocorticoid receptor agonist dexamethasone (DEX) (0.3 mg/kg), or glucose (GLU) (320 mg/kg) immediately after training. There was an impairment of inhibitory avoidance retention in the MK-801-SAL, MK-801-EPI, MK-801-NAL, MK-801-DEX, and MK-801-GLU groups. There was an enhancement of retention in the SAL-EPI, SAL-NAL, SAL-DEX, and SAL-GLU groups. A control experiment showed that the amnestic effects of MK-801 could not be attributed to decreased reactivity to the foot shock. The results suggest that memory-enhancing treatments directed at modulatory mechanisms do not reverse the memory impairment induced by NMDA receptor blockade.     

Activation of nociceptin opioid peptide (NOP) receptor impairs contextual fear learning in mice through glutamatergic mechanisms

The present study investigated whether the selective nociceptin opioid peptide (NOP) receptor agonist, Ro64-6198, impairs acquisition of fear conditioning through glutamatergic mechanisms. Systemic administration of Ro64-6198 (0.3 and 1 mg/kg) or the non-competitive NMDA receptor antagonist, MK-801 (0.03 and 0.1 mg/kg) prior to conditioning severely impaired contextual but not cued fear learning in C57BL/6N mice. When administered together at sub-effective doses, Ro64-6198 (0.5 mg/kg) and MK-801 (0.05 mg/kg), synergistically impaired contextual fear learning, but left cued fear learning intact. We next used the immediate shock deficit paradigm (ISD) to examine the effects of Ro64-6198 and MK-801 on contextual memory formation in the absence of the foot-shock. As expected, naive mice that were shocked briefly after being placed in the training chamber displayed no contextual fear conditioning. This learning deficit was elevated by prior exposure of mice to the training context. Furthermore, administration of Ro64-6198 and MK-801, either separately at amnesic doses (1 mg/kg and 0.1 mg/kg, respectively) or concomitantly at sub-effective doses (0.5 mg/kg and 0.05 mg/kg, respectively) significantly reduced the facilitating effects of context preexposure. These findings demonstrate the existence of functional antagonism between NOP and NMDA receptors that predominantly contributes to modulation of conditioned fear learning which involves spatial-processing demands.     

Differential involvement of NMDA and AMPA receptors within the nucleus accumbens in consolidation of information necessary for place navigation and guidance strategy of mice

Recent evidence now points to a role of glutamate transmission within the nucleus accumbens (Nacc) in spatial learning and memory. Unfortunately, the role of the distinct classes of glutamate receptors within this structure in mediating the different steps of the memorization process is not clear. The aim of this study therefore was to further investigate this issue, trying to assess the involvement of the two classes of glutamate receptors within the Nacc in consolidation of spatial information using an associative spatial task, the water maze. For this purpose, focal injections of the NMDA antagonist, AP-5, and of the AMPA antagonist, DNQX, have been performed immediately after the training phase, and mice have been tested for retention 24 h later. Two different versions of the water-maze task have been used: In the place version, animals could learn the position of the platform using visual distal cues, and in the cue version, the location of the platform was indicated by a single proximal cue. The results demonstrated that posttraining NMDA receptor blockade affects mice response in the place but not in the cue water-maze task. On the contrary, AMPA receptor blockade induced no effect in either version of the task. These data confirm a functional dissociation between glutamate receptors located in the Nacc in modulating spatial memory consolidation and indicate that they are specifically involved in consolidation of information necessary to acquire a place but not to a guidance strategy.     

Differential interaction of platelet-activating factor and NMDA receptor function in hippocampal and dorsal striatal memory processes

The interaction between platelet activating factor (PAF) and NMDA receptor function in hippocampal and dorsal striatal memory processes was examined. In both a hidden and a visible platform water maze task, peripheral post-training injection of MK-801 (0.05 mg/kg) impaired memory. Post-training intrahippocampal infusions of PAF (1.0 microg/0.5 microl) enhanced memory in the hidden platform task, while intradorsal striatal infusion of PAF (1.0 microg/0.5 microl) enhanced memory in the visible platform task. The memory impairing effects of post-training injection of MK-801 was blocked by concurrent intrahippocampal infusion of PAF. In contrast, post-training injection of MK-801 blocked the memory enhancing effects of concurrent intradorsal striatal infusion of PAF. The results suggest that (1) the memory enhancing effects of intracerebral PAF infusion involve an interaction with NMDA receptor function, and (2) the nature of this interaction may represent a differential mechanism mediating the distinct roles of the hippocampus and dorsal striatum in cognitive memory and stimulus-response habit formation, respectively.     

Xamoterol impairs hippocampus-dependent emotional memory retrieval via Gi/o-coupled β2-adrenergic signaling

Xamoterol, a partial β(1)-adrenergic receptor agonist, has been reported to impair the retrieval of hippocampus-dependent spatial reference memory in rats. In contrast, xamoterol restores memory retrieval in gene-targeted mice lacking norepinephrine (NE) and in a transgenic mouse model of Down syndrome in which NE levels are reduced. Restoration of retrieval by xamoterol in these two models complements the observation that NE and β(1) signaling are required for hippocampus-dependent retrieval of contextual and spatial reference memory in wild-type mice and rats. Additional evidence indicates that cAMP-mediated PKA and Epac signaling are required for the retrieval of hippocampus-dependent memory. As a result, we hypothesized that xamoterol has effects in addition to the stimulation of β(1) receptors that, at higher doses, act to counter the effects of β(1) signaling. Here we report that xamoterol-induced disruption of memory retrieval depends on β(2)-adrenergic receptor signaling. Interestingly, the impairment of memory retrieval by xamoterol is blocked by pretreatment with pertussis toxin, an uncoupling agent for G(i/o) signaling, suggesting that β(2) signaling opposes β(1) signaling during memory retrieval at the level of G protein and cAMP signaling. Finally, similar to the time-dependent roles for NE, β(1), and cAMP signaling in hippocampus-dependent memory retrieval, xamoterol only impairs retrieval for several days after training, indicating that its effects are also limited by the age of the memory. We conclude that the disruption of memory retrieval by xamoterol is mediated by G(i/o)-coupled β(2) signaling, which opposes the G(s)-coupled β(1) signaling that is transiently required for hippocampus-dependent emotional memory retrieval.     

The relationship of structural ischemic brain damage to neurobehavioural deficit: the effect of postischemic MK-801

Global cerebral ischemia is well known to cause neuronal necrosis in selectively vulnerable sectors of the hippocampus. Since the hippocampus of the rat is involved in spatial navigation, learning, and memory, selective deficits in these abilities may arise from ischemic brain damage. Previous studies have shown (a) a detectable neurobehavioural deficit due to ischemic brain damage limited to half of the CA1 sector of the hippocampus and (b) a reduction of ischemic neuronal necrosis with the noncompetitive N-methyl-D-Aspartate (NMDA) antagonist MK-801. This study was designed to determine the relationship between the improvement in structural brain damage in postischemically treated rats and any improvement in neurobehavioural performance, using a learning-set water task. Seventeen male Wistar rats received 10.5 min of forebrain ischemia induced by carotid clamping and hypotension. Brain temperature was estimated with probes in the temporalis muscle. Ten of these animals received no therapy (controls), and seven animals received 5 mg/kg MK-801 iv, 20 min postischemia. Six additional rats underwent a sham operation. Postischemic hypothermia was prevented with heating lamps. Four controls and one MK-801 treated animal died. The survivors were then tested on a place learning-set task in a swimming pool paradigm, and quantitative histopathologic analysis of their entire brains was done. The learning-set task revealed defects in spatial navigation, reflected as increased errors and latency in the performance of the untreated control rats. The performance of the MK-801 treated group progressively approached that of sham-operated rats over the course of testing and was significantly better than controls. Importantly, no long-term detrimental effect of MK-801 on the learning-set task performance was seen. Quantitative neuropathology revealed significantly less damage in the MK-801 treated group in all major brain regions. In the hippocampus, MK-801 treated animals showed hippocampal damage limited to the vulnerable portion of the pyramidal cell band comprising 48.8% of the CA1 pyramidal cells, as opposed to 72.4% in untreated controls. Extra-hippocampal damage was evident only in untreated control animals. MK-801 totally prevented neuronal necrosis in both the cerebral cortex and striatum and also prevented infarction in the neocortex and thalamus. Three conclusions emerge from the study. First, postischemic MK-801 mitigates structural brain damage in several brain regions in the absence of concomitant hypothermia. Second, neurobehavioural performance appears to be improved by MK-801 when performance trends are examined, but is somewhat less sensitive than quantitated histopathology due to compounding interanimal variation in performance abilities.(ABSTRACT TRUNCATED AT 400 WORDS)     

Appetitive memory reconsolidation depends upon NMDA receptor-mediated neurotransmission

Memory persistence is a dynamic process involving the reconsolidation of memories after their reactivation. Reconsolidation impairments have been demonstrated for many types of memories in rats, and signaling at N-methyl-d-aspartate (NMDA) receptors appears often to be a critical pharmacological mechanism. Here we investigated the reconsolidation of appetitive pavlovian memories reinforced by natural rewards. In male Lister Hooded rats, systemic administration of the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-SH-dibenzo{a,d}cyclohepten-5,10-imine maleate (MK-801, 0.1 mg/kg i.p.) either before or immediately following a brief memory reactivation session abolished the subsequent acquisition of a new instrumental response with sucrose conditioned reinforcement. However, only when injected prior to memory reactivation was MK-801 effective in disrupting the maintenance of a previously-acquired instrumental response with conditioned reinforcement. These results demonstrate that NMDA receptor-mediated signaling is required for appetitive pavlovian memory reconsolidation.     

Phosphodiesterase type 5 (PDE5) inhibition improves object recognition memory: indications for central and peripheral mechanisms

A promising target for memory improvement is phosphodiesterase type 5 (PDE5), which selectively hydrolyzes cyclic guanosine monophosphate (cGMP). In rodents, PDE5 inhibitors (PDE5-Is) have been shown to improve memory performance in many behavioral paradigms. However, it is questioned whether the positive effects in animal studies result from PDE5 inhibition in the central nervous system or the periphery. Therefore, we studied the effects of PDE5 inhibition on memory and determined whether compound penetration of the blood-brain barrier (BBB) is required for this activity. Two selective PDE5-Is, vardenafil and UK-343,664, were tested in the object recognition task (ORT) in both a MK-801- and scopolamine-induced memory deficit model, and a time-delay model without pharmacological intervention. Compounds were dosed 30 min before the learning trial of the task. To determine if the PDE5-Is crossed the BBB, their concentrations were determined in plasma and brain tissue collected 30 min after oral administration. Vardenafil improved object recognition memory in all three variants of the ORT. UK-343,664 was ineffective at either preventing MK-801-induced memory disruption or time-dependent memory decay. However, UK-343,664 attenuated the memory impairment of scopolamine. Vardenafil crossed the BBB whereas UK-343,664 did not. Further, co-administration of UK-343,664 and scopolamine did not alter the brain partitioning of either molecule. This suggests that the positive effect of UK-343,664 on scopolamine-induced memory decay might arise from peripheral PDE5 inhibition. The results herein suggest that there may be multiple mechanisms that mediate the efficacy of PDE5 inhibition to improve memory performance in tasks such as the ORT and that these involve PDE5 located both within and outside of the brain. To further elucidate the underlying mechanisms, the cellular and subcellular localization of PDE5 needs to be determined.     

Inhibition of PKA anchoring to A-kinase anchoring proteins impairs consolidation and facilitates extinction of contextual fear memories

Both genetic and pharmacological studies demonstrated that contextual fear conditioning is critically regulated by cyclic AMP-dependent protein kinase (PKA). Since PKA is a broad range protein kinase, a mechanism for confining its activity is required. It has been shown that intracellular spatial compartmentalization of PKA signaling is mediated by A-kinase anchoring proteins (AKAPs). Here, we investigated the role of PKA anchoring to AKAPs in different stages of the memory process (acquisition, consolidation, retrieval and extinction) using contextual fear conditioning, a hippocampus-dependent learning task. Mice were injected intracerebroventricularly or intrahippocampally with the membrane permeable PKA anchoring disrupting peptides St-Ht31 or St-superAKAP-IS at different time points during the memory process. Blocking PKA anchoring to AKAPs resulted in an impairment of fear memory consolidation. Moreover, disrupted PKA anchoring promoted contextual fear extinction in the mouse hippocampus. We conclude that the temporal and spatial compartmentalization of hippocampal PKA signaling pathways, as achieved by anchoring of PKA to AKAPs, is specifically instrumental in long-term contextual fear memory consolidation and extinction, but not in acquisition and retrieval.     

Prospective memory: Effects of divided attention on spontaneous retrieval

We examined the effects of divided attention on the spontaneous retrieval of a prospective memory intention. Participants performed an ongoing lexical decision task with an embedded prospective memory demand, and also performed a divided-attention task during some segments of lexical decision trials. In all experiments, monitoring was highly discouraged, and we observed no evidence that participants engaged monitoring processes. In Experiment 1, performing a moderately demanding divided-attention task (a digit detection task) did not affect prospective memory performance. In Experiment 2, performing a more challenging divided-attention task (random number generation) impaired prospective memory. Experiment 3 showed that this impairment was eliminated when the prospective memory cue was perceptually salient. Taken together, the results indicate that spontaneous retrieval is not automatic and that challenging divided-attention tasks interfere with spontaneous retrieval and not with the execution of a retrieved intention.     

A temporally distinct role for group I and group II metabotropic glutamate receptors in object recognition memory

Recognition memory, involving the ability to discriminate between a novel and familiar object, depends on the integrity of the perirhinal cortex (PRH). Glutamate, the main excitatory neurotransmitter in the cortex, is essential for many types of memory processes. Of the subtypes of glutamate receptor, metabotropic receptors (mGluRs) have received less study than NMDA receptors; thus, the reported experiments examined the role of mGluRs in familiarity discrimination in the rat PRH. Experiments 1 and 2 assessed the effects of systemic administration of MPEP, a group I mGluR (specifically mGluR5) antagonist, and/or LY341495, a group II mGluR antagonist, on a spontaneous object novelty preference task. Simultaneous antagonism of both group I and II mGluRs impaired familiarity discrimination following a 24-h but not a 15-min delay, while antagonism of either mGluR subtype alone had no effect at either delay. The impairment was in acquisition, as in Experiment 3 coadministration of MPEP and LY341495 did not affect recognition memory performance when administered either after the sample phase or prior to test. The impairment in long-term recognition memory was mediated by mGluRs in the PRH, as localized intracortical antagonism of group I and II mGluRs also produced a deficit (Experiment 4). No evidence was found for an involvement of group III mGluRs in the acquisition of long-term familiarity discrimination (Experiment 5). These findings establish that glutamatergic neurotransmission in the PRH via group I and II mGluRs is crucial for the acquisition, but not for the consolidation or retrieval of long-term object recognition memory.     

A one-trial inhibitory avoidance task to zebrafish: Rapid acquisition of an NMDA-dependent long-term memory

The behavioral tasks aiming to evaluate learning and memory mechanisms currently available to zebrafish (Danio rerio) involve long training sessions frequently along multiple days and are based on shuttle box or active-avoidance protocols, preventing a detailed analysis of cellular and molecular time-dependent processes involved in memory acquisition and consolidation. In order to explore zebrafish’s potential contribution to the characterization of the molecular machinery underlying learning and memory rapidly acquired and reliable paradigms are necessary. In this study we present a rapid and effective learning protocol in a single-trial inhibitory avoidance in zebrafish. In a simple apparatus, adult animals learned to refrain from swimming from a white into a dark compartment in order to avoid an electric shock during a single-trial training session that lasted less than 2 min. The resulting memory is robust, long-lasting and sensitive to NMDA-receptor antagonist MK-801 given in the tank water immediately after training. Experiments aiming to further characterize the events underlying memory formation, retrieval or extinction or those looking for cognitive profiling of mutants, neurotoxicological studies and disease models may benefit from this task, and together with complementary strategies available for zebrafish may significantly improve our current knowledge on learning and memory mechanisms.     

MK-801与环境线索交互作用对吗啡行为敏感化的影响

为探讨MK-801与环境线索交互作用对吗啡诱导行为敏感化的影响,将42只大鼠随机分为对照组,MK-801组,吗啡组（匹配和非匹配）和MK-801+吗啡组（匹配和非匹配）。行为敏感化模型建立分为发展期,戒断期和表达期三个阶段。实验结果发现：同时给予MK-801（0.1mg·kg-1）会促进吗啡（5mg·kg-1）诱导大鼠行为敏感化的发展,而且会使MK-801成为大鼠行为敏感化表达所必需的条件性刺激。MK-801的内部线索作用过强,从而削弱了环境的外部线索作用。研究结果表明：MK-801对吗啡诱导行为敏感化的影响存在状态依赖（state-dependency）现象,提示在NMDA受体与行为敏感化关系的研究中应考虑选择刺激特性更小的药物     

Strategy selection in a task with spatial and nonspatial components: effects of fimbria-fornix lesions in rats.

The main purpose of the present research was to investigate the ability of rats to learn a 12-arm radial maze task that requires the concurrent utilization of both spatial and intramaze cue information. The task involves in a single trial both place and cue learning as well as reference memory (RM) and working memory (WM). Since the animal can choose place and cue arms in any order, the strategies employed to learn the task can be studied as well as the kinds of memory errors that are made. The results of Experiment 1 showed that the number of errors made on the place and cue components of the task did not differ, and that more RM than WM errors were made early during learning. As the task was learned, the animals tended to choose the place arms before choosing the intramaze cue arms, thus suggesting that a spatial strategy was employed first followed by a cue strategy. In Experiment 2 lesions of the fimbria-fornix resulted in temporary impairments in both RM and WM that were especially apparent on the spatial component of the task. The lesioned rats also switched from choosing mostly place arms early during the trial to choosing more cue arms. While fimbria-fornix lesioned rats recovered from the memory impairments with training, the change in response strategy persisted throughout postoperative testing. The procedure of combining both spatial and non-spatial components concurrently in the same task should prove of value in studying response strategies in animals.     

The medial prefrontal cortex and memory of cue location in the rat

We developed a single-trial cue-location memory task in which rats experienced an auditory cue while exploring an environment. They then recalled and avoided the sound origination point after the cue was paired with shock in a separate context. Subjects with medial prefrontal cortical (mPFC) lesions made no such avoidance response, but both lesioned and control subjects avoided the cue itself when presented at test. A follow up assessment revealed no spatial learning impairment in either group. These findings suggest that the rodent mPFC is required for incidental learning or recollection of the location at which a discrete cue occurred, but is not required for cue recognition or for allocentric spatial memory.     

Implicit,long-term spatial contextual memory

Learning and memory of novel spatial configurations aids behaviors such as visual search through an implicit process called contextual cuing (M. M. Chun & Y. Jiang, 1998). The present study provides rigorous tests of the implicit nature ofcontextual cuing. Experiment 1 used a recognition test that closely matched the learning task, confirming that memory traces of predictive spatial context were not accessible to conscious retrieval. Experiment 2 gave explicit instructions to encode visual context during learning, but learning was not improved and conscious memory remained undetectable. Experiment 3 illustrates that memory traces for spatial context may persist for at least 1 week, suggesting along-term component of contextual cuing. These experiments indicate that the learning and memory of spatial context in the contextual cuing task are indeed implicit. The results have implications for understanding the neural substrate of spatial contextual learning, which may depend on an intact medial temporal lobe system that includes the hippocampus (Mi. M. Chun & E. A. Phelps, 1999).     

Acute predator stress impairs the consolidation and retrieval of hippocampus-dependent memory in male and female rats

We have studied the effects of an acute predator stress experience on spatial learning and memory in adult male and female Sprague-Dawley rats. All rats were trained to learn the location of a hidden escape platform in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. In the control (non-stress) condition, female rats were superior to the males in the accuracy and consistency of their spatial memory performance tested over multiple days of training. In the stress condition, rats were exposed to the cat for 30 min immediately before or after learning, or before the 24-h memory test. Predator stress dramatically increased corticosterone levels in males and females, with females exhibiting greater baseline and stress-evoked responses than males. Despite these sex differences in the overall magnitudes of corticosterone levels, there were significant sex-independent correlations involving basal and stress-evoked corticosterone levels, and memory performance. Most importantly, predator stress impaired short-term memory, as well as processes involved in memory consolidation and retrieval, in male and female rats. Overall, we have found that an intense, ethologically relevant stressor produced a largely equivalent impairment of memory in male and female rats, and sex-independent corticosterone-memory correlations. These findings may provide insight into commonalities in how traumatic stress affects the brain and memory in men and women.     

Distinct neural mechanisms mediate olfactory memory formation at different timescales

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.