Non-social Odors Research Articles

Effect of dietary phospholipid on the behavior in C57BL/6J mice

Nowadays phospholipids are widely used as hepatoprotective, neuroprotective and anti-stress drugs, as well as the dietary supplements. Besides, lecithin consisting up to 70% of the phospholipids mixture: phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidic acid, is the often component of food production as an emulsifier. Dose of these biologically active substances in the modern human diet could be quite high. Previously we have shown that chronic intestinal inflammation in Muc2-knockout mice induces behavioral changes along with the significant increase in the content of phospholipids in intestinal epithelial cells, particularly, phosphatidylcholine, phosphatidylserine and phosphatidic acid. Here we investigate the effects of long-term administration of a mixture of these phospholipids, as well as the effects of long-term administration of soy lecithin on the behavioral patterns in laboratory mice. Animals long-term taken a phospholipid mixture shows no normally observed preference towards females in the two intruders test (with female and male). In the social odor preference test, they also did not distinguish female and male odors, while non-social odors discrimination preserved. In addition, we identified a decrease in anxiety, obsessive traits, and schizophrenia-like behavior traits in these animals. Soy lecithin supplementation had similar effects on social behavior and compulsive traits, and increased aggression in males. Thus, long-term perinatal administration of either mixture of phospholipids (phosphatidylcholine, phosphatidylserine and phosphatidic acid) or soy lecithin can influence various aspects of behavior in mice.

Tropospheric ozone effect on olfactory perception and olfactory bulb dopaminergic interneuron excitability

Ozone (O3) forms in the Earth’s atmosphere, both naturally and by reactions of man-made air pollutants. Deleterious effects of O3 have been found in the respiratory system. Here, we examine whether O3 alters olfactory behavior and cellular properties in the olfactory system. For this purpose, mice were exposed to O3 at a concentration found in highly polluted city air [0.8 ppm], and the behavior elicited by social and non-social odors in habituation/dishabituation tests was assessed. In addition, the electrical responses of dopaminergic olfactory bulb (OB) neurons were also evaluated. O3 differentially compromises olfactory perception to odors: it reduces responses to social and non-social odors in Swiss Webster mice, while this effect was observed in C57BL/6 J mice only for some non-social odors. Additionally, O3 reduced the rate of spontaneous spike firing in periglomerular dopaminergic cells (PG-DA) of the OB. Because this effect could reflect changes in excitability and/or synaptic inputs, the ability of O3 to alter PG-DA spontaneous activity was also tested together with cell membrane resistance, membrane potential, rheobase and chronaxie. Taken together, our data suggest the ability of O3 to affect olfactory perception.

Aberrant Cortical Activity in 5xFAD Mice in Response to Social and Non-Social Olfactory Stimuli.

Neuroimaging studies investigating the behavioral and psychological symptoms of dementia (BPSD)- such as apathy, anxiety, and depression- have linked some of these symptoms with altered neural activity. However, inconsistencies in operational definitions and rating scales, limited scope of assessments, and poor temporal resolution of imaging techniques have hampered human studies. Many transgenic (Tg) mouse models of Alzheimer's disease (AD) exhibit BPSD-like behaviors concomitant with AD-related neuropathology, allowing examination of how neural activity may relate to BPSD-like behaviors with high temporal and spatial resolution. To examine task-dependent neural activity in the medial prefrontal cortex (mPFC) of AD-model mice in response to social and non-social olfactory stimuli. We previously demonstrated age-related decreases in social investigation in Tg 5xFAD females, and this reduced social investigation is evident in Tg 5xFAD females and males by 6 months of age. In the present study, we examine local field potential (LFP) in the mPFC of awake, behaving 5xFAD females and males at 6 months of age during exposure to social and non-social odor stimuli in a novel olfactometer. Our results indicate that Tg 5xFAD mice exhibit aberrant baseline and task-dependent LFP activity in the mPFC- including higher relative delta (1-4 Hz) band power and lower relative power in higher bands, and overall stronger phase-amplitude coupling- compared to wild-type controls. These results are consistent with previous human and animal studies examining emotional processing, anxiety, fear behaviors, and stress responses, and suggest that Tg 5xFAD mice may exhibit altered arousal or anxiety.

Phospholipid supplementation inhibits male and female odor discrimination in mice.

Dietary phospholipids (PLs) are promising supplements that are commonly found as natural food ingredients and emulsifier additives. The present study aimed to evaluate the effect of major PLs found in food supplements on social behavior in mice. In this study, the effect of short-term high dietary PL content was studied in terms of social odor discrimination and social interactions with male and female intruders in male mice. We used odor discrimination and habituation tests to demonstrate that PL-fed male mice tend to lose preference toward female odor and fail to discriminate against socially significant scents. At the same time, test animals recognize non-social odors. We also found that PL affected the social behavior of the test males, who tend to behave indiscriminately toward male and female intruders during direct contact. Brain metabolomic profiling revealed no major changes in the intermediary metabolism or neurotransmitter biosynthesis. At the same time, intranasal PL application resembled the effects of dietary supplementation. These data suggest that certain PL might suppress pheromone perception in the olfactory system and affect the sense of socially important odor cues.

Biologic that disrupts PDE11A4 homodimerization in hippocampus CA1 reverses age-related cognitive decline of social memories in mice

Age-related abnormalities in phosphodiesterase 11A (PDE11A), which degrades 3′,5′-cAMP/cGMP and is enriched in the ventral hippocampus (VHIPP), drive age-related cognitive decline (ARCD) of social memories. Age-related PDE11A4 ectopically accumulates within the membrane compartment and in filamentous structures termed ghost axons. Previous studies show that expressing an isolated PDE11A4-GAF-B binding domain disrupts homodimerization and reverses aging-like PDE11A4 accumulations in vitro. Here, we show that in vivo lentiviral expression of the isolated PDE11A4-GAFB domain in hippocampal CA1 of aged mice reverses age-related PDE11A4 accumulations and ARCD of social transmission of food preference memory (STFP). It also improves 7-day remote long-term memory for social odor recognition without affecting non-social odor recognition. In vitro studies show that disrupting homodimerization does not alter the catalytic activity of PDE11A4 but may reverse age-related decreases in cGMP by relocating PDE11A4 from a cGMP-rich to a cAMP-rich pool independently of other intramolecular relocation signals (PDE11A4-pS162). Altogether, these data suggest that a biologic designed to disrupt PDE11A4 homodimerization may hold therapeutic potential for age-related PDE11A4 proteinopathies.

Social odor discrimination and its enhancement by associative learning in the hippocampal CA2 region

Although the hippocampus is crucial for social memory, how social sensory information is combined with contextual information to form episodic social memories remains unknown. Here, we investigated the mechanisms for social sensory information processing using two-photon calcium imaging from hippocampal CA2 pyramidal neurons (PNs)-which are crucial for social memory-in awake head-fixed mice exposed to social and non-social odors. We found that CA2 PNs represent social odors of individual conspecifics and that these representations are refined during associative social odor-reward learning to enhance the discrimination of rewarded compared with unrewarded odors. Moreover, the structure of the CA2 PN population activity enables CA2 to generalize along categories of rewarded versus unrewarded and social versus non-social odor stimuli. Finally, we found that CA2 is important for learning social but not non-social odor-reward associations. These properties of CA2 odor representations provide a likely substrate for the encoding of episodic social memory.

Odor exploration behavior of the domestic pig (Sus scrofa) as indicator of enriching properties of odors.

Although the sense of smell in pigs is widely recognized as being highly developed, surprisingly little is known about their sensory ability. This study aimed to (a) identify which non-social odors pigs were able to detect and distinguish between, (b) investigate the types of behavior expressed when exploring odors and, (c) compare pigs' responses to the different odors to evaluate their interest in the odors. Growing pigs (N = 192) of crossbred commercial breeds were enrolled in the experiment (32-110 days of age, weighing 64.9 ± 10.1kg). Littermate pairs of opposite sex were tested in test pens with two odor insertion points in the pen wall, 55 cm apart. All pigs were habituated to the test pens and experimenters. Twelve odors were tested (eight essential oils and four synthetic perfumes) in groups of three odors, with each pig pair tested once with one set of three odors (all possible orders of the three odors were tested on 24 pairs in total), always against a non-odor control (demineralized water). In a test, each of the three odors were presented during three trials in a row (a total of 9 trials per test; trial duration: 1 min; inter-trial breaks: 2 min; total test duration: 25 min). Response variables included: duration of sniffing, feeding-related behavior (licking, biting and rooting), agonistic behavior (biting, displacement and pushing) and no approach of the odor or control, recorded throughout each 1-min odor presentation. All pigs sniffed an odor less when repeatedly presented (LMM: all odors P < 0.05), and significantly longer at the subsequent presentation of a new odor [LMM (3rd vs. 1st presentations): P < 0.001]. Specific odor and odor type (essential oil vs. synthetic perfume) had no significant effect on sniffing duration. Overall, feeding-related behavior and agonistic behavior were expressed significantly more when pigs explored the odor compared with the control insertion point (Paired t-tests: P < 0.001), and specific odor only affected the expression of feeding-related behavior. Collectively, pigs express sniffing, agonistic, and feeding-related behavior when exploring odors, which suggests that pigs perceive odors of non-social origin as a resource. Odors may thus constitute relevant enrichment material for pigs.

The Effect of Odor Valence on Facial Attractiveness Judgment: A Preliminary Experiment

The role of social odors on human social interactions, including face evaluation, has been widely indicated. However, for nonsocial odors, there has not been a consistent conclusion. Therefore, this study aimed to verify the effect of suprathreshold nonsocial odors on facial attractiveness judgment when the visual input is ambiguous. We designed a 3 (odor valence: neutral, pleasant, and unpleasant) × 7 (continuous levels of morphed fuzziness of attractiveness: 37.5% to 62.5%) within-subject experiment. A total of 30 participants (18 females) completed the whole experiment simultaneously for three consecutive days. The results showed that faces presented with pleasant and neutral odors were judged as significantly more attractive than those with unpleasant odors. The intervention effect of odor valence on facial attractiveness differed by fuzzy attractiveness levels. Results also suggested that male faces were perceived as more attractive than female faces no matter the odor conditions. The results of this study provide evidence to support the cross-modal emotion integration effect of olfaction and vision. Follow-up studies need to be conducted to reveal the underlying mechanism of odor valence on visual fact attractive judgment.

Energizing effects of bupropion on effortful behaviors in mice under positive and negative test conditions: modulation of DARPP-32 phosphorylation patterns

Motivational symptoms such as anergia, fatigue, and reduced exertion of effort are seen in depressed people. To model this, nucleus accumbens (Nacb) dopamine (DA) depletions are used to induce a low-effort bias in rodents tested on effort-based decision-making. We evaluated the effect of the catecholamine uptake blocker bupropion on its own, and after administration of tetrabenazine (TBZ), which blocks vesicular storage, depletes DA, and induces depressive symptoms in humans. Male CD1 mice were tested on a 3-choice-T-maze task that assessed preference between a reinforcer involving voluntary physical activity (running wheel, RW) vs. sedentary activities (sweet food pellet intake or a neutral non-social odor). Mice also were tested on the forced swim test (FST), two anxiety-related measures (dark–light box (DL), and elevated plus maze (EPM)). Expression of phosphorylated DARPP-32 (Thr34 and Thr75) was evaluated by immunohistochemistry as a marker of DA-related signal transduction. Bupropion increased selection of RW activity on the T-maze. TBZ reduced time running, but increased time-consuming sucrose, indicating an induction of a low-effort bias, but not an effect on primary sucrose motivation. In the FST, bupropion reduced immobility, increasing swimming and climbing, and TBZ produced the opposite effects. Bupropion reversed the effects of TBZ on the T-maze and the FST, and also on pDARPP32-Thr34 expression in Nacb core. None of these manipulations affected anxiety-related parameters. Thus, bupropion improved active behaviors, which were negatively motivated in the FST, and active behaviors that were positively motivated in the T-maze task, which has implications for using catecholamine uptake inhibitors for treating anergia and fatigue-like symptoms.

Prioritization of social information by the basolateral amygdala in rats

The amygdala is a collection of nuclei that support adaptive social behavior and are implicated in disorders such as autism. The basolateral complex of the amygdala (BLA), a main subdivision of the amygdala, influences fear responses, motivated behavior, and memory of emotional events via its communication with other amygdalar nuclei and with other brain regions such as the prefrontal cortex, striatum, and hippocampus. The specific role of the BLA in responses to social stimuli is less clear. The present study of female rats investigated the role of the BLA in responding to socially-relevant information by asking how inactivation of the BLA with bilateral infusions of the GABA receptor agonist muscimol would affect spontaneous exploration of wood blocks scented either with conspecific male or female urine or with nonsocial odorants. Conspecific urine samples were used because urine conveys information about sex, health, social status, and reproductive state in rodents. The results revealed that BLA inactivation reduced female rats’ spontaneous preference for social odors over nonsocial odors, specifically for female urine. However, BLA inactivation did not generally impair rats’ ability to distinguish two odors from the same category (e.g., urine odors from two different male rats). The results indicate that the BLA is important for responding to salience of social stimuli but not for discriminating between different individuals, a result that has important implications for amygdalar modulation of downstream attention, motivation, and memory processes for social stimuli.

Odor discrimination in terrestrial and aquatic environments in California sea lions (Zalophus californianus) living in captivity

Pinnipeds, as any mammal species, use multimodal signals, including olfactory ones, to ensure vital functions. Thus, some pinniped species seem able to use olfaction in both social and foraging contexts and to discriminate between different odors in air including both natural and artificial odors, but studies on that topic remain scarce. Here, we studied the olfactory capabilities of California sea lions living in captivity at La Flèche Zoo (France) in both terrestrial and aquatic environments. We used two categories of odors: social odors (from familiar individuals of the same group, unfamiliar individuals from another Zoo, animal zookeepers and a terrestrial carnivore) and non-social odors (food and odors identified as repellents in certain vertebrates). Several behavioral parameters were measured and analyzed as the number and duration of contact with the odor, mouth openings, vocalizations (air only) and air bubble production (water only). Our results, although limited by the low number of animals monitored (n = 5), suggest that California sea lions are able to discriminate between different odors both in the air and under water. In the aquatic environment, the process allowing the perception of odors remains to be characterized. Applications to this work could be considered in captive conditions as well as in the wild.

Absence of Both Thyroid Hormone Transporters MCT8 and OATP1C1 Impairs Neural Stem Cell Fate in the Adult Mouse Subventricular Zone.

SummaryAdult neural stem cell (NSC) generation in vertebrate brains requires thyroid hormones (THs). How THs enter the NSC population is unknown, although TH availability determines proliferation and neuronal versus glial progenitor determination in murine subventricular zone (SVZ) NSCs. Mice display neurological signs of the severely disabling human disease, Allan-Herndon-Dudley syndrome, if they lack both MCT8 and OATP1C1 transporters, or MCT8 and deiodinase type 2. We analyzed the distribution of MCT8 and OATP1C1 in adult mouse SVZ. Both are strongly expressed in NSCs and at a lower level in neuronal cell precursors but not in oligodendrocyte progenitors. Next, we analyzed Mct8/Oatp1c1 double-knockout mice, where brain uptake of THs is strongly reduced. NSC proliferation and determination to neuronal fates were severely affected, but not SVZ-oligodendroglial progenitor generation. This work highlights how tight control of TH availability determines NSC function and glial-neuron cell-fate choice in adult brains.

Social and olfactory experiences modify neuronal morphology of orbital frontal cortex.

Structural modifications in the dendritic morphology of neurons occur following many forms of experience, including exposure to drugs, complex housing, and training in specific behavioral tasks. The present study examined morphological changes in orbitofrontal (OFC) and medial prefrontal cortex (mPFC) neurons of female rats following experience with a variety of social partners or nonsocial olfactory stimuli. We reasoned that experience with various social partners or olfactory stimuli, and the associated behavioral adaptations, would drive structural modifications in prefrontal cortex neurons engaged by these stimuli. Social experience was manipulated by providing rats with a novel cage-mate or housing the animal with the same cage-mate throughout the study. Similarly, olfactory experience was manipulated by introducing novel, nonsocial odors in the home cage or exposing the animals to the same home-cage odor throughout the study. Both forms of experience resulted in altered dendritic morphology in OFC neurons, whereas morphological changes in mPFC were comparatively small and limited to changes in spine density. These observations indicate that OFC and mPFC neurons respond differently to social and nonsocial olfactory stimulation in adulthood and join the growing body of data illustrating differential effects of experience on structural plasticity in OFC and mPFC. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Preference for Exercise vs. More Sedentary Reinforcers: Validation of an Animal Model of Tetrabenazine-Induced Anergia.

Physical activities can have intrinsic motivational or reinforcing properties. The choice to engage in voluntary physical activity is undertaken in relation to the selection of other alternatives, such as sedentary behaviors, drugs, or food intake. The mesolimbic dopamine (DA) system plays a critical role in behavioral activation or exertion of effort, and DA antagonism or depletion induces anergia in effort-based decision-making tasks. However, little is known about the neural mechanisms underlying the decision-making processes that establish preferences for sedentary vs. activity-based reinforcers. In the present work with male CD1 mice, we evaluated the effect of tetrabenazine (TBZ), a DA-depleting agent, on a three-choice T-maze task developed to assess preference between reinforcers with different behavioral activation requirements and sensory properties [i.e., a running wheel (RW) vs. sweet pellets or a neutral nonsocial odor]. We also studied the effects of TBZ on the forced swim test (FST), which measures climbing and swimming in a stressful setting, and on anxiety tests [dark-light (DL) box and elevated plus maze (EPM)]. In the three-choice task, TBZ reduced time running in the wheel but increased time spent consuming sucrose, thus indicating reduced activation but relatively intact sucrose reinforcement. The effect of TBZ was not mimicked by motivational manipulations that change the value of the reinforcers, such as making the RW aversive or harder to move, food-restricting the animals, inducing a binge-like eating pattern, or introducing social odors. In the FST, TBZ decreased time climbing (most active behavior) and increased immobility but did not affect anxiety in the DL or EPM. These results indicate that the three-choice T-maze task could be useful for assessing DA modulation of preferences for exercise based on activation and effort requirements, differentiating those effects from changes in preference produced by altering physical requirements, food restriction state, and stress during testing.

A Computational Model of Oxytocin Modulation of Olfactory Recognition Memory

Social recognition in mammals depends on complex interactions between sensory and other brain areas as well as modulatory inputs by specific neuropeptides such as oxytocin (OXT). Social recognition memory specifically has been shown to depend among others on olfactory processing, and can be probed using methods similar to those used when probing non-social odor memory. We here use a computational model of two interconnected olfactory networks in the mouse, the olfactory bulb (OB) and anterior olfactory nucleus, to propose a mechanism for olfactory short-term recognition memory and its modulation in social situations. Based on previous experiments, we propose one early locus for memory to be the OB. During social encounters in mice, pyramidal cells in the anterior olfactory nucleus, themselves driven by olfactory input, are rendered more excitable by OXT release, resulting in stronger feedback to OB local interneurons. This additional input to the OB creates stronger dynamics and improves signal-to-noise ratio of odor responses in the OB proper. As a consequence, mouse social olfactory memories are more strongly encoded and their duration is modulated.

Haploinsufficiency of autism causative gene Tbr1 impairs olfactory discrimination and neuronal activation of the olfactory system in mice

BackgroundAutism spectrum disorders (ASD) exhibit two clusters of core symptoms, i.e., social and communication impairment, and repetitive behaviors and sensory abnormalities. Our previous study demonstrated that TBR1, a causative gene of ASD, controls axonal projection and neuronal activation of amygdala and regulates social interaction and vocal communication in a mouse model. Behavioral defects caused by Tbr1 haploinsufficiency can be ameliorated by increasing neural activity via D-cycloserine treatment, an N-methyl-D-aspartate receptor (NMDAR) coagonist. In this report, we investigate the role of TBR1 in regulating olfaction and test whether D-cycloserine can also improve olfactory defects in Tbr1 mutant mice.MethodsWe used Tbr1+/− mice as a model to investigate the function of TBR1 in olfactory sensation and discrimination of non-social odors. We employed a behavioral assay to characterize the olfactory defects of Tbr1+/− mice. Magnetic resonance imaging (MRI) and histological analysis were applied to characterize anatomical features. Immunostaining was performed to further analyze differences in expression of TBR1 subfamily members (namely TBR1, TBR2, and TBX21), interneuron populations, and dendritic abnormalities in olfactory bulbs. Finally, C-FOS staining was used to monitor neuronal activation of the olfactory system upon odor stimulation.ResultsTbr1+/− mice exhibited smaller olfactory bulbs and anterior commissures, reduced interneuron populations, and an abnormal dendritic morphology of mitral cells in the olfactory bulbs. Tbr1 haploinsufficiency specifically impaired olfactory discrimination but not olfactory sensation. Neuronal activation upon odorant stimulation was reduced in the glomerular layer of Tbr1+/− olfactory bulbs. Furthermore, although the sizes of piriform and perirhinal cortices were not affected by Tbr1 deficiency, neuronal activation was reduced in these two cortical regions in response to odorant stimulation. These results suggest an impairment of neuronal activation in olfactory bulbs and defective connectivity from olfactory bulbs to the upper olfactory system in Tbr1+/− mice. Systemic administration of D-cycloserine, an NMDAR co-agonist, ameliorated olfactory discrimination in Tbr1+/− mice, suggesting that increased neuronal activity has a beneficial effect on Tbr1 deficiency.ConclusionsTbr1 regulates neural circuits and activity in the olfactory system to control olfaction. Tbr1+/− mice can serve as a suitable model for revealing how an autism causative gene controls neuronal circuits, neural activity, and autism-related behaviors.

Odor preference and olfactory memory are impaired in Olfaxin-deficient mice

Olfaxin, which is a BNIP2 and Cdc42GAP homology (BCH) domain-containing protein, is predominantly expressed in mitral and tufted (M/T) cells in the olfactory bulb (OB). Olfaxin and Caytaxin, which share 56.3% amino acid identity, are similar in their glutamatergic terminal localization, kidney-type glutaminase (KGA) interaction, and caspase-3 substrate. Although the deletion of Caytaxin protein causes human Cayman ataxia and ataxia in the mutant mouse, the function of Olfaxin is largely unknown. In this study, we generated Prune2 gene mutant mice (Prune2Ex16−/−; knock out [KO] mice) using the CRISPR/Cas9 system, during which the exon 16 containing start codon of Olfaxin mRNA was deleted. Exon 16 has 80 nucleotides and is contained in four of five Prune2 isoforms, including PRUNE2, BMCC1, BNIPXL, and Olfaxin/BMCC1s. The levels of Olfaxin mRNA and Olfaxin protein in the OB and piriform cortex of KO mice significantly decreased. Although Prune2 mRNA also significantly decreased in the spinal cord, the gross anatomy of the spinal cord and dorsal root ganglion (DRG) was intact. Further, disturbance of the sensory and motor system was not observed in KO mice. Therefore, in the current study, we examined the role of Olfaxin in the olfactory system where PRUNE2, BMCC1, and BNIPXL are scarcely expressed. Odor preference was impaired in KO mice using opposite-sex urinary scents as well as a non-social odor stimulus (almond). Results of the odor-aversion test demonstrated that odor-associative learning was disrupted in KO mice. Moreover, the NMDAR2A/NMDAR2B subunits switch in the piriform cortex was not observed in KO mice. These results indicated that Olfaxin may play a critical role in odor preference and olfactory memory.

Gonadal hormones, but not sex, affect the acquisition and maintenance of a Go/No-Go odor discrimination task in mice

In mice, olfaction is crucial for identifying social odors (pheromones) that signal the presence of suitable mates. We used a custom-built olfactometer and a thirst-motivated olfactory discrimination Go/No-Go (GNG) task to ask whether discrimination of volatile odors is sexually dimorphic and modulated in mice by adult sex hormones. Males and females gonadectomized prior to training failed to learn even the initial phase of the task, which involved nose poking at a port in one location obtaining water at an adjacent port. Gonadally intact males and females readily learned to seek water when male urine (S+) was present but not when female urine (S−) was present; they also learned the task when non-social odorants (amyl acetate, S+; peppermint, S−) were used. When mice were gonadectomized after training the ability of both sexes to discriminate urinary as well as non-social odors was reduced; however, after receiving testosterone propionate (castrated males) or estradiol benzoate (ovariectomized females), task performance was restored to pre-gonadectomy levels. There were no overall sex differences in performance across gonadal conditions in tests with either set of odors; however, ovariectomized females performed more poorly than castrated males in tests with non-social odors. Our results show that circulating sex hormones enable mice of both sexes to learn a GNG task and that gonadectomy reduces, while hormone replacement restores, their ability to discriminate between odors irrespective of the saliency of the odors used. Thus, gonadal hormones were essential for both learning and maintenance of task performance across sex and odor type.

Genetic loss of diazepam binding inhibitor in mice impairs social interest.

Neuropsychiatric disorders in which reduced social interest is a common symptom, such as autism, depression, and anxiety, are frequently associated with genetic mutations affecting γ-aminobutyric acid (GABA)ergic transmission. Benzodiazepine treatment, acting via GABA type-A receptors, improves social interaction in male mouse models with autism-like features. The protein diazepam binding inhibitor (DBI) can act as an endogenous benzodiazepine, but a role for DBI in social behavior has not been described. Here, we investigated the role of DBI in the social interest and recognition behavior of mice. The responses of DBI wild-type and knockout male and female mice to ovariectomized female wild-type mice (a neutral social stimulus) were evaluated in a habituation/dishabituation task. Both male and female knockout mice exhibited reduced social interest, and DBI knockout mice lacked the sex difference in social interest levels observed in wild-type mice, in which males showed higher social interest levels than females. The ability to discriminate between familiar and novel stimulus mice (social recognition) was not impaired in DBI-deficient mice of either sex. DBI knockouts could learn a rotarod motor task, and could discriminate between social and nonsocial odors. Both sexes of DBI knockout mice showed increased repetitive grooming behavior, but not in a manner that would account for the decrease in social investigation time. Genetic loss of DBI did not alter seminal vesicle weight, indicating that the social interest phenotype of males lacking DBI is not due to reduced circulating testosterone. Together, these studies show a novel role of DBI in driving social interest and motivation.

Behavioral Phenotyping for Autism Spectrum Disorders in Mice.

Autism spectrum disorder (ASD) represents a heterogeneous group of disorders characterized by alterations in three behavioral symptom domains: Social interactions, verbal and nonverbal communication, and repetitive behaviors. Increasing prevalence of ASD in recent years suggests that exposure to environmental toxicants may be critical in modulating etiology of this disease. As clinical diagnosis of autism still relies on behavioral evaluation, it is important to be able to assess similar behavioral traits in animal models, to provide biological plausibility of associations between environmental exposures and ASD. Rodents naturally exhibit a large number of behaviors that can be linked to similar behaviors in human. In this unit, behavioral tests are described that are relevant to the domains affected in ASD. For the repetitive domain, the T-maze spontaneous alternation test and marble burying test are described. For the communication domain, neonatal ultrasonic vocalization and olfactory habituation test toward social and non-social odor are described. Finally, for the sociability domain, the three-chambered social preference test and the reciprocal interaction test are presented. © 2017 by John Wiley & Sons, Inc.