The perirhinal-entorhinal cortex, but not the hippocampus, is critical for expression of individual recognition in the context of the Coolidge effect

The Coolidge effect is a phenomenon in which males show renewed sexual interest in a novel female following copulation to satiety with another female. In golden hamsters, this phenomenon depends on the ability to recognize conspecifics using chemosensory cues processed through the main olfactory system. Here we tested whether olfactory targets in the hippocampal system support this natural form of recognition memory. Male hamsters received ibotenic acid lesions of the perirhinal-entorhinal cortex (PR-ENT) or hippocampus (H) and were allowed to copulate to satiety with a female conspecific, then were presented with two anesthetized females, the familiar mate and an unfamiliar female that copulated with another male. Sham-operated and H-lesioned subjects preferentially investigated the novel female, indicating intact recognition of individual identity. By contrast, PR-ENT-lesioned males failed to discriminate familiar and novel females, and this deficit could not be attributed to abnormal copulatory behavior during mating. All subjects were able to detect and discriminate between female odors when presented in isolation during a habituation-discrimination test, indicating that behavioral deficits shown by PR-ENT males were not due to anosmia or a general investigatory deficit. Thus, the perirhinal-entorhinal cortex, but not the hippocampus, is critical for the recognition of familiar conspecifics in this naturalistic situation. This study reveals an essential role for the perirhinal-entorhinal cortex, but not the hippocampus, in a natural form of recognition memory within the social behavior of hamsters. The findings show a strikingly similar pattern to the effects of selective damage to the same brain regions on performance in standard recognition memory tasks by rats and monkeys. Therefore, the present data extend our understanding of the differential role of structures of the hippocampal memory system, showing continuity across species and between formal laboratory tests and the function of memory in natural social behavior.     

Discrimination of social odors and their locations: role of lateral entorhinal area

Discrimination of individual conspecifics by their odors has been reported for many mammalian species, but little information is available on the brain mechanisms underlying such discrimination. A previous study reported that large parahippocampal lesions, centered on entorhinal cortex but extending into adjacent areas of the brain, eliminated female hamsters' ability to discriminate the flank gland odors of different individuals, as tested with habituation-dishabituation methods. The current study examined the effects of lesions restricted to the lateral entorhinal area on such discriminations. Female hamsters were tested in several types of habituation procedure that differed across a sequence of trials in the locations of familiar and novel social odors. Discrimination of two individuals' odors depended on the sequences of locations of the odors, indicating that odor identity and location were simultaneously salient to female hamsters. Lesions of lateral entorhinal area interfered with this spatial-olfactory discrimination. When confounding spatial cues were eliminated, hamsters did discriminate between novel and familiar odors, and lesions in the entorhinal area did not eliminate this ability. Thus, although the lateral entorhinal area is not necessary for individual odor discrimination, it is involved in processing odor-place combinations.     

Individual recognition of female hamsters by males: role of chemical cues and of the olfactory and vomeronasal systems

Sexually satiated male hamsters preferred to investigate and to mount an anesthetized, estrous, novel female over a similarly presented female with which the male had become satiated (the Coolidge effect); likewise, such males preferred a novel female recently mated with another male over the familiar female but showed no preference between fresh and mated novel females. Thus the Coolidge effect is at least partly dependent on discrimination of a new female by chemical cues. Another experiment indicated that transfer of a male's own scent during mating is not involved in discrimination between familiar and novel females. Flank gland secretion of females were sufficient for individual discrimination by males, whereas head region scents and vaginal secretions were not sufficient. The presence of female's flank glands was not, however, necessary for such discrimination. Lesions of or removal of the vomeronasal organ did not disrupt the preferences of sexually satiated males for a novel female, but elimination of main olfactory system function by ZnSO4 treatment of the olfactory mucosa did abolish such preferences. Thus olfactory cues are sufficient for individual discrimination of novel females by sexually satiated male hamsters, and such recognition leads to increased sexual arousal. These processes are mediated by the main olfactory system but not the vomeronasal accessory-olfactory system.     

Lesions that functionally disconnect the anterior and posterodorsal sub-regions of the medial amygdala eliminate opposite-sex odor preference in male Syrian hamsters (Mesocricetus auratus)

In many rodent species, such as Syrian hamsters, reproductive behavior requires neural integration of chemosensory information and steroid hormone cues. The medial amygdala (MA) processes both of these signals through anatomically distinct sub-regions; the anterior region (MeA) receives substantial chemosensory input, but contains few steroid receptor-labeled neurons, whereas the posterodorsal region (MePD) receives less chemosensory input, but contains a dense population of steroid receptors. Importantly, these sub-regions have considerable reciprocal connections, and the goal of this experiment was therefore to determine whether interactions between MeA and MePD are required for male hamsters' preference to investigate female over male odors. To functionally disconnect MeA and MePD, males received unilateral lesions of MeA and MePD within opposite brain hemispheres. Control males received either unilateral lesions of MeA and MePD within the same hemisphere or sham surgery. Odor preferences were measured using a 3-choice apparatus, which simultaneously presented female, male and clean odor stimuli; all tests were done under conditions that either prevented or allowed contact with the odor sources. Under non-contact conditions, males with asymmetrical lesions investigated female and male odors equally, whereas males in both control groups preferred to investigate female odors. Under contact conditions, all groups investigated female odors longer than male odors, although males with asymmetrical lesions displayed decreased investigation of female odors compared to sham males. These data suggest that MeA–MePD interactions are critical for processing primarily the volatile components of social odors and highlight the importance of input from the main olfactory system (MOS) to these nuclei in the regulation of reproductive behavior. More broadly, these results support the role of the MA in integrating chemosensory and hormone information, a process that may underlie social odor processing in a variety of behavioral contexts.     

The role of the hippocampal system in social odor discrimination and scent-marking in female golden hamsters (Mesocricetus auratus)

Female golden hamsters (Mesocricetus auratus) received aspiration lesions of the parahippocampal region (PARA) or electrolytic lesions of the fimbria-fornix (FNX) and were tested for their (a) discrimination between odors of individual males in a habituation-discrimination task, (b) preference for male over female odors, and (c) scent-marking in response to conspecific odors. Both lesion groups habituated to repeated presentations of a male's odor. However, only FNX females discriminated between scents of individual males, whereas PARA females did not. Neither lesion eliminated female preferences for male odors. Females with FNX lesions showed decreased levels of scent marking, but those with PARA lesions had more subtle deficits. Thus, the PARA, but not the subcortical connections of the hippocampus, is critical for discrimination of the odors of individuals.     

Effects of vomeronasal organ removal on individual odor discrimination, sex-odor preference, and scent marking by female hamsters

Removal of the vomeronasal organ (VNX) did not eliminate the ability of female hamsters to discriminate between individual male's flank gland or urine odors in a habituation/discrimination task nor did it impair preference for male odors over female odors from a distance. Vomeronasal organ removal did reduce overall levels of investigation of flank gland odor in the habituation/discrimination task. Although VNX females did not show severe impairments in the frequency of either flank or vaginal marking in response to odors, they did show an abnormal pattern of marking. VNX females, unlike shams, did not flank mark more to female odors than to male odors, nor did they vaginal mark more to male odors than to female odors. Thus, the vomeronasal organ in female hamsters appears to be important for differences in scent marking toward male and female odors, but is not essential for discrimination of individual odors or for preferences for male over female odors.     

The vomeronasal organ is involved in discrimination of individual odors by males but not by females in golden hamsters

The vomeronasal organ (VNO) has a wide variety of functions in terrestrial vertebrates, some of which involve responses to classical pheromones whereas others do not. We examined the role of the VNO in discrimination of individual differences in odors of male and female golden hamsters using a habituation paradigm. Removal of the VNO resulted in elimination of the ability of male hamsters to discriminate between some individually distinctive odors (e.g., flank gland secretion), but not others (e.g., urine). In females, such lesions had no effect. The type of test trial also influenced the results; in test trials employing a single, novel odor, removal of the VNO in males did have an effect but in test trials in which both the novel and the familiar odor were presented, VNO removal had no effect. It is concluded that (a) there is a sex difference in the role of the VNO in the discrimination of individual odors, (b) the role of the VNO in discrimination of individual odors varies from odor to odor, and (c) deficits due to VNO removal are more readily observed in more difficult tasks.     

Lesions centered on the medial amygdala impair scent-marking and sex-odor recognition but spare discrimination of individual odors in female golden hamsters.

The medial amygdala (Me) has been implicated in various social behaviors that depend on chemosensory cues, but its precise role in discriminating and learning social odors is not known. Female golden hamsters (Mesocricetus auratus) received electrolytic lesions of the Me or sham surgery and were tested for their ability to (a) discriminate between odors of individual males in a habituation-discrimination task, (b) show preferences for male over female odors in a Y maze, and (c) scent-mark in response to male and female odors. All females discriminated between scents of individual males. In contrast, Me lesions eliminated female preferences for male odors in a Y maze. Females with Me lesions also showed a substantial reduction in vaginal marking and virtually no flank marking in response to odors. Thus, the Me in female hamsters is critical for differential investigation of opposite-sex odors and for scent-marking behavior but is not involved in discrimination between odors of individuals.     

Rats assess degree of relatedness from human odors

Despite widespread interest in the evolutionary implications of human olfactory communication, the mechanisms underlying human odor production are still poorly understood. Previous studies have demonstrated that human odor cues are related to variations in the major histocompatibility complex, but it is unclear whether odors are associated with overall genotypic variation. In this study, we investigated whether more closely related humans produce more similar odor cues. To assess objective odor qualities we tested odor similarity using rats in a habituation–discrimination paradigm. Rats were first habituated to a referent human odor and were then presented with two test odors obtained from individuals related in different degrees to the referent. Investigation times for each odor were compared. Because rats investigate novel odors longer than familiar odors, we were able to determine which test odor the rats perceived as more similar to the referent human odor. For six of ten odor donor families, rats investigated the odor of the less closely related individual significantly longer than that of the more closely related individual, and investigation durations were in the expected direction for all families. These results indicate that similarity of human odor cues is associated with degree of genetic relatedness, with more closely related humans producing more similar odor cues. This study supports the hypothesis that odor cues provide information regarding degree of relatedness and may thus affect a wide variety of human behaviors, including kin preferences, nepotism, and mate choice.     

Ultrasounds in neonatal rats: Novel,predator and conspecific odor cues

Neonatal rat ultrasound repetition rates were monitored in response to 6 odor cues, including 1 novel, 2 predator, and 3 conspecific olfactory stimuli. Contrary to predictions of previous studies, predator odor did not elicit consistently low call rates. A significant difference was detected between litters tested with the same odor cue for the foreign and predator odor treatments. Odor was the only significant effect to explain differences in neonatal ultrasonic responses to conspecific odor treatments. Call rates recorded for the novel lactating female odor were significantly greater than those for the home bedding and adult male odors. Odors associated with the home cage or with an adult male elicited low call rates.     

Olfactory experience and the development of odor preference and vaginal marking in female Syrian hamsters

Rodent reproductive behavior relies heavily on odor processing, and evidence suggests that many odor-guided sexual behaviors are shaped by prior experience. We sought to determine if exposure to male odors during development is required for the adult expression of proceptive sexual behavior toward male odors in female Syrian hamsters. Exposure to male odors was restricted in na?ve subjects by removing all male siblings from the litter at three to five days of age. Control litters were also culled, but included equal numbers of male and female pups. As adults, na?ve females displayed investigatory preferences toward male odors in a Y-maze that were comparable to control females; this preference was observed whether contact with the odor stimuli was prevented of allowed. In contrast, na?ve females vaginal scent-marked equally toward male and female volatile odors, suggesting an inability to target behavior toward sexually relevant odors. However, na?ve females marked preferentially toward male odors when allowed to contact the odor stimuli. These results provide evidence for the experience-dependent development of vaginal marking behavior toward volatile components of sexual odors. Furthermore, they suggest that distinct mechanisms regulate the development of odor preferences and vaginal marking behavior in this species.     

Effect of sex steroids and coital experience on ferrets' preference for the smell,sight and sound of conspecifics

Previous research showed that ferrets of both sexes recognize potential opposite-sex mates on the basis of volatile body odors. We compared the ability of estrogen and androgen treatments to activate a preference in gonadectomized male and female ferrets for distal cues (volatile body odors alone or volatile odors+sight+sounds) from male versus female stimulus ferrets using an airtight Y-maze and a "stimulus proximity" or a "discrete trials" testing paradigm. Sexually naive, gonadectomized male and female ferrets that received either testosterone propionate (TP) or estradiol benzoate (EB) spent equal time in proximity to goal boxes that provided either volatile odors alone or odors+sight+sounds of male and female stimulus animals. After they received coital experience, male and female subjects (treated with either EB or TP) showed a significant preference for both types of opposite-sex stimuli. When discrete trials tests were given to these ferrets prior to receiving coital experience, EB-treated females preferred to approach odor only cues, as well as odors+sight+sounds of stimulus males, and this preference was further strengthened after coital experience. Sexually naive, TP-treated males preferred to approach volatile odor cues from stimulus females; however, these animals showed an equal preference for odors+sight+sounds of stimulus females and males. Again, after coital experience, males' preference for both sets of cues from stimulus females was significantly enhanced. Thus, in sexually naive ferrets, discrete trials, but not stimulus proximity tests, revealed a preference for distal cues (body odors with or without concurrent sight and sounds) from opposite-sex conspecifics in subjects of both sexes. Coital experience significantly enhanced these preferences for heterosexual distal cues under both testing paradigms.     

Hippocampus and olfactory discrimination learning: effects of entorhinal cortex lesions on olfactory learning and memory in a successive-cue, go-no-go task

Three experiments assessed the effect of entorhinal cortex lesions on olfactory learning and memory using a successive-cue olfactory discrimination paradigm. In contrast to the results of other studies that used a simultaneous-cue paradigm, lesions of the entorhinal cortex facilitated rats' acquisition of individual odor discrimination problems, with no impairment in memory for the individual odors across both short (24-hr) and long (65-day) retention intervals and despite limited training. When considered together with previous observations of facilitation or impairment in learning after damage to the hippocampal system, the present data suggest that the hippocampus is preferentially involved in encoding relations among multiple stimuli. By this account, facilitation of performance is due to an interaction between hippocampal system dysfunction and task conditions that hinder direct comparisons among cues.     

Source and Item Memory for Odors and Objects in Children and Young Adults

Recall and recognition memory for odors are poorer in children than in adolescents. In addition, children perform worse than young adults on source memory tasks using visual and auditory stimuli. However, source memory for odor stimuli has not been examined in children. This study investigated source and item memory for odors and objects in children (7–10 years old) and young adults (18–24 years old). During the study phase, 1 male and 1 female experimenter (sources) randomly presented either 16 odors or 16 objects to the participant. Presentation alternated between sources so that each source presented 8 stimuli. Once the 16 stimuli were presented, the sources exited and a third experimenter began the test phase. To assess item recognition memory, a stimulus from the study phase and a novel stimulus were presented to the participant who was asked to choose the stimulus presented during the study phase. Source memory was assessed with the 8 stimuli from the study phase not used in the item memory task. The experimenter presented a stimulus and asked whether the male or female experimenter had presented the stimulus during the study phase. Results indicate that difference scores between item and source memory for odors were significantly larger for children than for young adults, indicating poorer source memory for children than adults. Difference scores for objects did not distinguish between groups. It has been suggested that the frontal lobes play a critical role in source memory and odor memory—a brain region that continues to develop into adolescence. Poor performance among children on the source memory task for odors may be due in part to immaturity of the frontal lobes.     

Olfactory tests as possible probes for detecting and monitoring Alzheimer's disease

One of the characteristics of Alzheimer's disease is the early loss of neurons in pathways involved in processing olfactory information. Olfactory function was assessed in subjects with Alzheimer's disease using a conventional Smell Identification Test and a simple three odor match-to-sample problem. The patients exhibited a diminished capacity to identify common odors but were severely impaired in their ability to use novel odors in a match-to-sample task. Subjects with Parkinson's disease had a severe deficit for identifying common odors with the majority scoring as anosmic. Multiple sclerosis was not accompanied by detectable changes in olfactory functioning. The results of the Alzheimer's group are similar to recent animal studies that have shown lesions of the piriform-entorhinal cortex produce a variety of memory deficits that are particularly acute in tasks involving novel odors.     

Perseveration of attention to conspecific odors and novel objects in castrated gerbils

Castrated male and female gerbils were tested for odor preference and for attention to conspecific odors and a novel object. Castrated gerbils housed with sham-operates preferred home odors, discriminated between two groups of male gerbils by olfactory cues, and perseverated in attention to odors of male gerbils and to a novel object. Similar perseveration to male conspecific odors was shown in gerbils given injections of L-DOPA (30 mg/kg). Combined treatment (castration and L-DOPA) resulted in additive effects on perseveration. This research challenges two general hypotheses of gonadal hormone function. The first, that changes in odor preference after castration are due to a loss in testicular androgen, is insufficient, because (1) female as well as male gerbils showed similar perseveration to odors, (2) there was a significant correlation between LH and duration of investigation of male conspecific odors, and (3) L-DOPA, the dopamine precurser, also caused perseveration to conspecific odors. The second, that gonadal hormones are responsible for persistence of attention, cannot be broadly generalized, because castration with resultant elevation of LH and regression of ventral glands resulted in perseveration of attention in male and female gerbils.     

Olfactory representations by Drosophila mushroom body neurons

Learning and memory has been studied extensively in Drosophila using behavioral, molecular, and genetic approaches. These studies have identified the mushroom body as essential for the formation and retrieval of olfactory memories. We investigated odor responses of the principal neurons of the mushroom body, the Kenyon cells (KCs), in Drosophila using whole cell recordings in vivo. KC responses to odors were highly selective and, thus sparse, compared with those of their direct inputs, the antennal lobe projection neurons (PNs). We examined the mechanisms that might underlie this transformation and identified at least three contributing factors: excitatory synaptic potentials (from PNs) decay rapidly, curtailing temporal integration, PN convergence onto individual KCs is low ( approximately 10 PNs per KC on average), and KC firing thresholds are high. Sparse activity is thought to be useful in structures involved in memory in part because sparseness tends to reduce representation overlaps. By comparing activity patterns evoked by the same odors across olfactory receptor neurons and across KCs, we show that representations of different odors do indeed become less correlated as they progress through the olfactory system.     

Increased dopamine after mating impairs olfaction and prevents odor interference with pregnancy

In rodents, social odor sensing influences female reproductive status by affecting neuroendocrine cascades. The odor of male mouse urine can induce ovulation or block pregnancy within 3 d post coitus. Females avoid the action of such olfactory stimuli after embryonic implantation. The mechanisms underlying these changes are unknown. Here we report that shortly after mating, a surge in dopamine in the mouse main olfactory bulb impairs the perception of social odors contained in male urine. Treatment of females at 6.5 d post coitus with a dopamine D2 receptor antagonist restores social odor sensing and favors disruption of pregnancy by inhibition of prolactin release, when administered in the presence of alien male urine odors. These results show that an active sensory barrier blocks social olfactory cues detrimental to pregnancy, consistent with the main olfactory bulb being a major relay through which social odor modulates reproductive status.     

Odor modulation of ventral scent gland marking in the Mongolian gerbil

Gerbil odors were allowed to accumulate in individual home cages for several months in order to provide stable olfactory stimuli that might modulate the number of ventral scent gland marks produced by both male and female Mongolian gerbils. Male marking levels for most test conditions were 2-3 times larger than those in females. In general, the relative patterns of responsiveness to particular odors were similar in both sexes. The number of scent marks in home cages was significantly smaller than the number obtained in clean cages. This suppression was not strongly dependent on the odors emanating from an individual's own ventral gland sebum. Marking levels in the home cages of other gerbils were substantially higher than those seen in the test animal's own cage and were maximal in the home cages of other males. Behaviorally receptive females marked at significantly higher levels in home, clean, and conspecific cages than did nonreceptive females. Conspecific urine odors, especially those from females, increased marking levels significantly over those obtained in home cages. In males, home cage marking was significantly enhanced by the presence of a female. Females, on the other hand, marked at similar levels in home cages whether a potential mating partner was present or not. Both sexes showed significant reductions in marking levels in another's cage if the resident animal was present. These results suggest that when sufficient gerbil-related odors are available to a test animal, its rate of scent-marking is altered, depending on the particular odor environment. Some gerbil-related odors increase marking levels, whereas others decrease marking. Scent-marking then, like other olfactory guided behaviors and odor preferences, is context specific.