Neural correlates of individual odor preference in Drosophila

Behavior varies even among genetically identical animals raised in the same environment. However, little is known about the circuit or anatomical underpinnings of this individuality. Drosophila olfaction is an ideal system for discovering the origins of behavioral individuality among genetically identical individuals. The fly olfactory circuit is well-characterized and stereotyped, yet stable idiosyncrasies in odor preference, neural coding, and neural wiring are present and may be relevant to behavior. Using paired behavior and two-photon imaging measurements, we show that individual odor preferences in odor-vs-air and odor-vs-odor assays are predicted by idiosyncratic calcium dynamics in Olfactory Receptor Neurons (ORNs) and Projection Neurons (PNs), respectively. This suggests that circuit variation at the sensory periphery determines individual odor preferences. Furthermore, paired behavior and immunohistochemistry measurements reveal that variation in ORN presynaptic density also predicts odor-vs-odor preference. This point in the olfactory circuit appears to be a locus of individuality where microscale variation gives rise to idiosyncratic behavior. To unify these results, we constructed a leaky-integrate-and-fire model of 3,062 neurons in the antennal lobe. In these simulations, stochastic fluctuations at the glomerular level, like those observed in our ORN immunohistochemistry, produce variation in PN calcium responses with the same structure as we observed experimentally, the very structure that predicts idiosyncratic behavior. Thus, our results demonstrate how minute physiological and structural variations in a neural circuit may produce individual behavior, even when genetics and environment are held constant.

Validation of New Methods of Using Simulated Whole-Body Movements as Implicit Indicators of Sound and Odor Preferences

Would you get close to a stinky perfume bottle or to a loudspeaker producing noise? In this paper, we present two procedures that allowed us to assess the ability of auditory and olfactory cues to elicit automatic approach/avoidance reactions toward their sources. The procedures resulted from an adaptation of the Visual Approach/Avoidance by the Self Task (VAAST; Rougier et al., 2018), a task having the peculiarity of simulating approach/avoidance reactions by using visual feedback coming from the whole-body movements. In the auditory VAAST (Experiment 1), participants were instructed to move forward or backward from a loudspeaker that produced spoken words differentiated by their level of distortion and thus by their hedonic value. In the olfactory VAAST (Experiment 2), participants were asked to move forward or backward from a perfume bottle that delivered pleasant and unpleasant odors. We expected, consistent with the approach/avoidance compatibility effect, shorter latencies for approaching positive stimuli and avoiding negative stimuli. In both experiments, we found an effect of the quality of the emotional stimulus on forward actions of participants, with undistorted words and pleasant odors inducing faster forward movements compared with that for distorted words and unpleasant odors. Notably, our results further suggest that the VAAST can successfully be used with implicit instructions, i.e., without requiring participants to explicitly process the valence of the emotional stimulus (in Experiment 1) or even the emotional stimulus itself (in Experiment 2). The sensitivity of our procedures is analyzed and its potential in cross-modal and (contextualized) consumer research discussed.

Puberty is a Critical Period for Vomeronasal Organ Mediation of Socio-sexual Behavior in Mice

Genetic disruption of the vomeronasal organ (VNO), an organ responsible for pheromone processing, drastically alters socio-sexual behavior in mice. However, it is not known whether the VNO has a role during the pubertal organizational period when sex-typical socio-sexual behaviors emerge, or if disruption of the organ in adulthood is sufficient to alter socio-sexual behavior. To bypass the lifelong VNO disruption of genetic knockout models, we surgically ablated the VNO of male and female mice either during the peripubertal period [postnatal day (PND) 28–30] or adulthood (PND 58–60), with sham controls at both ages. We ruled out anosmia via the buried food test and assessed sexual odor preferences by simultaneously exposing mice to same- and opposite-sex soiled-bedding. We then measured territorial aggression with the resident-intruder paradigm and assessed sexual behavior in response to an encounter with an estrus-induced female. Neural activity approximated by FOS-immunoreactivity along the VNO-accessory olfactory pathway was measured in response to opposite-sex odors. We found that peripubertal VNO ablation decreased sexual odor preferences and neural activity in response to opposite-sex odors, and drastically reduced territorial aggression in male mice. Conversely, adult VNO ablation resulted in subtle differences in sexual odor preferences compared with sham controls. Regardless of the VNO condition, mice displayed sex-typical copulatory behaviors. Together, these results suggest that puberty is a critical period in development whereby the VNO contributes to the sexual differentiation of behavior and neural response to conspecific odors.

Sensory neurons expressing the atypical olfactory receptor guanylyl cyclase D are required for the acquisition of odor preferences by mice in diverse social contexts

ABSTRACTAnimals use social communication to learn important information from conspecifics that can guide appropriate behavioral choices. For example, during the social transmission of food preference (STFP), conspecific semiochemicals detected by mouse olfactory sensory neurons (OSNs) expressing the atypical olfactory receptor guanylyl cyclase D (GC-D+ OSNs) promote the acquisition of food preferences in the recipient animal, mitigating the risk of ingesting food contaminated with toxins or pathogens. However, it is unclear if GC-D+ OSNs mediate preference learning outside this specific context. Here, we report that GC-D+ OSNs are required for the acquisition of odor preferences by both adult and juvenile mice, and that GC-D-dependent preference could be formed for conditionally aversive odors. We used a two-choice olfactory behavioral test to assess odor preferences in adult Gucy2d +/+, +/- and -/- mice that encountered novel odors together with GC-D+ OSN stimuli (guanylin family peptides), during social investigation of a live conspecific, or during suckling as pups. Gucy2d +/+ and +/-mice (which express functional GC-D), but not Gucy2d -/- littermates, successfully acquire a preference for the demonstrated odor in any of these behavioral paradigms. Mice could even acquire a GC-D-dependent preference for odors to which they had recently formed a conditioned aversion. Together, these results demonstrate that GC-D+ OSNs mediate the acquisition of socially-transmitted odor preferences in different social and experiential contexts and at different life stages.

Marsupial and monotreme milk—a review of its nutrient and immune properties

All mammals are characterized by the ability of females to produce milk. Marsupial (metatherian) and monotreme (prototherian) young are born in a highly altricial state and rely on their mother’s milk for the first part of their life. Here we review the role and importance of milk in marsupial and monotreme development. Milk is the primary source of sustenance for young marsupials and monotremes and its composition varies at different stages of development. We applied nutritional geometry techniques to a limited number of species with values available to analyze changes in macronutrient composition of milk at different stages. Macronutrient energy composition of marsupial milk varies between species and changes concentration during the course of lactation. As well as nourishment, marsupial and monotreme milk supplies growth and immune factors. Neonates are unable to mount a specific immune response shortly after birth and therefore rely on immunoglobulins, immunological cells and other immunologically important molecules transferred through milk. Milk is also essential to the development of the maternal-young bond and is achieved through feedback systems and odor preferences in eutherian mammals. However, we have much to learn about the role of milk in marsupial and monotreme mother-young bonding. Further research is warranted in gaining a better understanding of the role of milk as a source of nutrition, developmental factors and immunity, in a broader range of marsupial species, and monotremes.

Alterations in odor hedonics in the 5XFAD Alzheimer’s disease mouse model and the influence of sex

Olfactory impairments, including deficits in odor detection, discrimination, recognition, and changes in odor hedonics are reported in the early stages of Alzheimer’s disease (AD). Rodent models of AD display deficits in odor learning, detection, and discrimination – recapitulating the clinical condition. However, the impact of familial AD genetic mutations on odor hedonics is unknown. We tested 2-, 4-, and 6-months old 5XFAD (Tg6799) mice in the five-port odor multiple-choice task designed to assay a variety of odor-guided behaviors, including odor preferences/hedonics. We found that 5XFAD mice investigated odors longer than controls, an effect that was driven by 6-months old mice. Interestingly, this effect was carried by females in the 5XFAD group, who investigated odors longer than age-matched males. Upon examining behavior directed towards individual odors to test for aberrant odor preferences, we uncovered that 5XFAD females at several ages displayed heightened preferences towards some of the odors, indicating aberrant hedonics. We observed no impairments in the ability to engage in the task in 5XFAD mice. Taken together, 5XFAD mice, particularly 5XFAD females, displayed prolonged odor investigation behavior and enhanced preferences to certain odors. The data provide insight into hedonic alterations which may occur in AD mouse models, and how these are influenced by biological sex.

Encoding Innately Recognized Odors via a Generalized Population Code

SummaryOdors carrying intrinsic values often trigger instinctive aversive or attractive responses. It is not known how innate valence is encoded. An intuitive model suggests that the information is conveyed through specific channels in hardwired circuits along the olfactory pathway, insulated from influences of other odors, to trigger innate responses. Here we show that in mice, mixing innately aversive or attractive odors with a neutral odor, and surprisingly, mixing two odors with the same valence, abolish the innate behavioral responses. Recordings from the olfactory bulb indicate that odors are not masked at the level of peripheral activation and glomeruli independently encode components in the mixture. In contrast, crosstalk among the mitral/tufted cells changes their patterns of activity such that those elicited by the mixtures can no longer be linearly decoded as separate components. The changes in behavioral and mitral/tufted cell responses are associated with reduced activation of brain areas linked to odor preferences. Thus, crosstalk among odor channels at the earliest processing stage in the olfactory pathway leads to re-coding of odor identity to abolish valence associated with the odors. These results are inconsistent with insulated labeled lines and support a model of a common mechanism of odor recognition for both innate and learned valence associations.

Idiosyncratic neural coding and neuromodulation of olfactory individuality inDrosophila

Innate behavioral biases and preferences can vary significantly among individuals of the same genotype. Though individuality is a fundamental property of behavior, it is not currently understood how individual differences in brain structure and physiology produce idiosyncratic behaviors. Here we present evidence for idiosyncrasy in olfactory behavior and neural responses inDrosophila. We show that individual femaleDrosophilafrom a highly inbred laboratory strain exhibit idiosyncratic odor preferences that persist for days. We used in vivo calcium imaging of neural responses to compare projection neuron (second-order neurons that convey odor information from the sensory periphery to the central brain) responses to the same odors across animals. We found that, while odor responses appear grossly stereotyped, upon closer inspection, many individual differences are apparent across antennal lobe (AL) glomeruli (compact microcircuits corresponding to different odor channels). Moreover, we show that neuromodulation, environmental stress in the form of altered nutrition, and activity of certain AL local interneurons affect the magnitude of interfly behavioral variability. Taken together, this work demonstrates that individualDrosophilaexhibit idiosyncratic olfactory preferences and idiosyncratic neural responses to odors, and that behavioral idiosyncrasies are subject to neuromodulation and regulation by neurons in the AL.