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.

Serotonin and Dopamine Mimic Glucose-Induced Reinforcement in C. elegans: Potential Role of NSM Neurons and the Serotonin Subtype 4 Receptor

Food produces powerful reinforcement that can lead to overconsumption and likely contributes to the obesity epidemic. The present studies examined molecular mechanisms mediating food-induced reinforcement in the model system C. elegans. After a 1-h training session during which food (bacteria) is paired with the odorant butanone, odor preference for butanone robustly increased. Glucose mimicked this effect of bacteria. Glucose-induced odor preference was enhanced similarly by prior food withdrawal or blocking glucose metabolism in the presence of food. Food- and glucose-induced odor preference was mimicked by serotonin signaling through the serotonin type-4 (5-HT4) receptor. Dopamine (thought to act primarily through a D1-like receptor) facilitated, whereas the D2 agonist bromocriptine blocked, food- and glucose-induced odor preference. Furthermore, prior food withdrawal similarly influenced reward produced by serotonin, dopamine, or food, implying post-synaptic enhancement of sensitivity to serotonin and dopamine. These results suggest that glucose metabolism plays a key role in mediating both food-induced reinforcement and enhancement of that reinforcement by prior food withdrawal and implicate serotonergic signaling through 5-HT4 receptor in the re-enforcing properties of food.

Acquisition of innate odor preference depends on spontaneous and experiential activities during critical period

Animals possess an inborn ability to recognize certain odors to avoid predators, seek food, and find mates. Innate odor preference is thought to be genetically hardwired. Here we report that acquisition of innate odor recognition requires spontaneous neural activity and is influenced by sensory experience during early postnatal development. Genetic silencing of mouse olfactory sensory neurons during the critical period has little impact on odor sensitivity, discrimination, and recognition later in life. However, it abolishes innate odor preference and alters the patterns of activation in brain centers. Exposure to innately recognized odors during the critical period abolishes the associated valence in adulthood in an odor-specific manner. The changes are associated with broadened projection of olfactory sensory neurons and expression of axon guidance molecules. Thus, a delicate balance of neural activity is needed during the critical period in establishing innate odor preference and convergent axon input is required to encode innate odor valence.

Prenatal EDCs Impair Mate and Odor Preference and Activation of the VMN in Male and Female Rats

Environmental endocrine-disrupting chemicals (EDCs) disrupt hormone-dependent biological processes. We examined how prenatal exposure to EDCs act in a sex-specific manner to disrupt social and olfactory behaviors in adulthood and underlying neurobiological mechanisms. Pregnant rat dams were injected daily from embryonic day 8 to 18 with 1 mg/kg Aroclor 1221 (A1221), 1 mg/kg vinclozolin, or the vehicle (6% DMSO in sesame oil). A1221 is a mixture of polychlorinated biphenyls (weakly estrogenic) while vinclozolin is a fungicide (anti-androgenic). Adult male offspring exposed to A1221 or vinclozolin, and females exposed to A1221, had impaired mate preference behavior when given a choice between 2 opposite-sex rats that differed by hormone status. A similar pattern of impairment was observed in an odor preference test for urine-soaked filter paper from the same rat groups. A habituation/dishabituation test revealed that all rats had normal odor discrimination ability. Because of the importance of the ventrolateral portion of the ventromedial nucleus (VMNvl) in mate choice, expression of the immediate early gene product Fos was measured, along with its co-expression in estrogen receptor alpha (ERα) cells. A1221 females with impaired mate and odor preference behavior also had increased neuronal activation in the VMNvl, although not specific to ERα-expressing neurons. Interestingly, males exposed to EDCs had normal Fos expression in this region, suggesting that other neurons and/or brain regions mediate these effects. The high conservation of hormonal, olfactory, and behavioral traits necessary for reproductive success means that EDC contamination and its ability to alter these traits has widespread effects on wildlife and humans.

Locus coeruleus patterns differentially modulate learning and valence in rat via the ventral tegmental area and basolateral amygdala respectively

ABSTRACTThe locus coeruleus (LC), the main source of forebrain norepinephrine, produces phasic and tonic firing patterns that are theorized to have distinct functional consequences. However, how different firing modes affect learning and valence coding of sensory information are unknown. Here bilateral optogenetic activation of rat LC neurons using 10-Hz phasic trains of either 300 msec or 10 sec accelerates acquisition of a food-rewarded similar odor discrimination, but not a dissimilar odor discrimination, consistent with LC-supported enhanced pattern separation and plasticity. Similar odor discrimination learning is impaired by noradrenergic blockade in the piriform cortex (PC). However, here 10-Hz LC phasic light-mediated learning facilitation is prevented by a dopaminergic antagonist in the PC, or by ventral tegmental area (VTA) silencing with lidocaine, suggesting an LC-VTA-PC dopamine circuitry mediates 10-Hz phasic learning facilitation. Tonic stimulation at 10 Hz did not alter odor discrimination acquisition, and was less effective in activating VTA DA neurons. For valence encoding, tonic stimulation at 25 Hz induced freezing, anxiety and conditioned odor aversion, while 10-Hz phasic stimulation produced an odor preference consistent with positive valence. Noradrenergic blockade in the basolateral amygdala (BLA) prevented conditioned odor preference and aversion induced by 10-Hz phasic and 25-Hz tonic light respectively. CTB retro-labeling showed relatively larger engagement of nucleus accumbens projecting neurons over central amygdala projecting neurons in the BLA with 10-Hz LC phasic activation, compared to 25-Hz tonic. These outcomes argue that LC pauses, as well as LC firing frequencies, differentially influence both target networks and behaviour.

Fucose Ameliorates Tryptophan Metabolism and Behavioral Abnormalities in a Mouse Model of Chronic Colitis

Growing evidence suggests that intestinal mucosa homeostasis impacts immunity, metabolism, the Central Nervous System (CNS), and behavior. Here, we investigated the effect of the monosaccharide fucose on inflammation, metabolism, intestinal microbiota, and social behavior in the Dextran Sulfate Sodium (DSS)-induced chronic colitis mouse model. Our data show that chronic colitis is accompanied by the decrease of the serum tryptophan level and the depletion of the intestinal microbiota, specifically tryptophan-producing E. coli and Bifidobacterium. These changes are associated with defects in the male mouse social behavior such as a lack of preference towards female bedding in an odor preference test. The addition of fucose to the test animals’ diet altered the bacterial community, increased the abundance of tryptophan-producing E. coli, normalized blood tryptophan levels, and ameliorated social behavior deficits. At the same time, we observed no ameliorating effect of fucose on colon morphology and colitis. Our results suggest a possible mechanism by which intestinal inflammation affects social behavior in male mice. We propose fucose as a promising prebiotic, since it creates a favorable environment for the beneficial bacteria that promote normalization of serum tryptophan level and amelioration of the behavioral abnormalities in the odor preference test.

Acquisition of Innate Odor Preference Depends on Spontaneous and Experiential Activities During Critical Period

Animals possess inborn ability to recognize certain odors, which enables them to seek food, avoid predators and find mates even in the absence of prior experiences. The establishment of innate odor preference has been thought to be genetically hardwired. Here we report that the acquisition of innate odor recognition requires spontaneous neural activity and is influenced by sensory experience during early postnatal development. Genetic silencing of mouse olfactory sensory neurons during the developmental critical period has little impact on odor sensitivity, odor discrimination and recognition later in life. However, it abolishes innate odor preference and alters the patterns of activation in brain centers. Moreover, exposure to an innately aversive odor during the critical period abolishes aversion in adulthood in an odor specific manner. The loss of innate aversion is associated with broadened projection of OSNs expressing the cognate receptor such that they innervate ectopic glomeruli in the olfactory bulb. These results indicate that a delicate balance of neural activity is required during critical period in establishing innate odor preference and that ectopic projection is a convergent mechanism to alter innate odor valence.

Spaced training forms complementary long-term memories of opposite valence inDrosophila

Forming long-term memory (LTM) in many cases requires repetitive experience spread over time. InDrosophila, aversive olfactory LTM is optimal following spaced training, multiple trials of differential odor conditioning with rest intervals. Studies often compare memory after spaced to that after massed training, same number of trials without interval. Here we show flies acquire additional information after spaced training, forming an aversive memory for the shock-paired odor and a ‘safety-memory’ for the explicitly unpaired odor. Safety-memory requires repetition, order and spacing of the training trials and relies on specific subsets of rewarding dopaminergic neurons. Co-existence of the aversive and safety memories can be measured as depression of odor-specific responses at different combinations of junctions in the mushroom body output network. Combining two particular outputs appears to signal relative safety. Learning a complementary safety memory thereby augments LTM performance after spaced training by making the odor preference more certain.