social memory mice

doi: 10.1111/gbb.12169, Suzuki, A., Fukushima, H., Mukawa, T., Toyoda, H., Wu, L.-J., Zhao, M.-G., et al. Inhibitor of the tyrosine phosphatase STEP reverses cognitive deficits in a mouse model of Alzheimer’s disease. Basal ganglia circuit loops, dopamine and motivation: a review and enquiry. In fact, an acute pharmacological inhibition of STEP after intraperitoneal injection of 10 mg/Kg TC-2153 (Xu et al., 2014) in WT mice had no effect in most parameters analyzed in the open field, light-dark box task or three-chamber social test (Chatterjee et al., 2018). The apparatus consisted of two opposing open arms (58 × 8 cm) crossed by two opposing enclosed arms (58 × 8 × 12 cm), and an open 8 × 8 cm square in the center. Six months old male (C57BL/6J background) STEP KO (Venkitaramani et al., 2009) and WT mice were housed in groups of 2–5 animals per cage, maintained under standard housing conditions, 12 h light/dark schedule (lights on at 08:00 am) with food and water ad libitum, 22 ± 2°C room temperature and 50%–70% humidity. Impairment of social behaviors in Arhgef10 knockout mice. Nonetheless, we cannot rule out the contribution of lack of dishabituation to a new stimulus in the absence of STEP. ; D2R: t(1,18) = 0.18, n.s., Figure 5E). Trying to conceive after a pregnancy loss, Circuit tweak enhances social memory in mice, Subscribe to get NIH Research Matters by email, Mailing Address: Cell. Strikingly, in another study, neither WT nor STEP KO mice showed social memory in the three-chamber sociability test (Goebel-Goody et al., 2012b). To determine whether STEP KO have a general recognition memory deficit we evaluated their object recognition memory using the NORT. Our data robustly demonstrated that STEP KO mice presented specific social memory impairment as indicated by the three-chamber sociability test, the social discrimination test, the 11-trial habituation/dishabituation social recognition test, and the novel object recognition test (NORT). SK3-overexpression drives sex-dimorphic working and social memory impairment in mice. doi: 10.1371/journal.pone.0127408, Lijam, N., Paylor, R., McDonald, M. P., Crawley, J. N., Deng, C., Herrup, K., et al. Experimental procedures were approved by the Local Ethical Committee of the University of Barcelona following European (2010/63/UE) and Spanish (RD53/2013) regulations for the care and use of laboratory animals. doi: 10.1097/fbp.0000000000000110, van Erp, A. M., and Miczek, K. A. Impaired social memories in 129P2 inbred mice are rescued by reduced Csk expression. AC designed the microdialysis studies, performed the experiments with GB and MM, and analyzed, interpreted data of microdialysis experiments, and wrote this section. Training phase. 13, 3064–3074. (2014). Indeed, it has been reported that social communication is affected by genotype, since social signaling from mice other than WT may elicit unusual social behaviors in the subject mice (Wood and Morton, 2015). doi: 10.1016/j.mcn.2015.12.009, Zhang, Y., Kurup, P., Xu, J., Carty, N., Fernandez, S. M., Nygaard, H. B., et al. It has been reported that STEP KO mice show improved cognitive performance in the Morris water maze and in the radial arm maze (Venkitaramani et al., 2011) as well as increased fear conditioning in the conditioning suppression food-motivated instrumental performance test (Olausson et al., 2012). Collectively, our findings indicate a role for the Fgf9 Y162C mutation in information processing and perception of aversive situations as well as in social memory. Social interaction was evaluated in the resident-intruder test as previously described (Lumley et al., 2000; Wood and Morton, 2015), with some modifications. The dorsal striatum plays a role in internally guided social behavior, the ventral striatum regulates social behavior by the integration of external social stimuli (Báez-Mendoza and Schultz, 2013; van den Bos, 2015), and the balance of 5-HT and DA levels determines the role of each striatal region in social behaviors (van den Bos, 2015). PLoS Biol. Eur. (A) Dominant and subordinate behavior of WT and STEP KO (n = 11–12) mice in the dominance tube test. In addition, the effect of ketamine on social memory was significantly attenuated in the olanzapine- and haloperidol-treated animals, rendering no difference between the mouse-exploration time after saline or ketamine ( p = 0.67 and p = 0.64, respectively). Behav. doi: 10.1016/j.brainresrev.2007.10.006, Olausson, P., Venkitaramani, D. V., Moran, T. D., Salter, M. W., Taylor, J. R., and Lombroso, P. J. Editor: Harrison Wein, Ph.D. Assistant Editors: Erin Bryant and Tianna Hicklin, Ph.D. NIH Research Matters is a weekly update of NIH research highlights reviewed by NIH’s experts. Striatal-enriched protein tyrosin phosphatase (STEP) knockout mice have enhanced hippocampal memory. 33, 2288–2298. STEP KO mice present behavioral despair. Group-housed mice were transferred to new home cages with two pieces of soft paper for nesting, and nests were assessed 24 h later on a rating scale of 1–5. Behav. Mol. An 8 –9-week-old C57BL/6J female was then introduced for four consecutive 1-min-long confrontations spaced by a 10-min interval dur-ing which the female was removed from the cage. doi: 10.1371/journal.pbio.1001923, Xu, J., Hartley, B. J., Kurup, P., Phillips, A., Topol, A., Xu, M., et al. doi: 10.1016/s0092-8674(00)80354-2, Lombroso, P. J., Murdoch, G., and Lerner, M. (1991). Moreover, the extracellular levels of dopamine (DA), but not serotonin (5-HT), were increased in the dorsal striatum of STEP KO mice. Nesting behavior was assessed by using a protocol modified from Deacon (2006). The results from the resident-intruder test indicated that STEP KO mice showed more interest in interacting with the barrier than WT mice during the habituation to the barrier (“genotype” effect t(1,21) = 7.31, p < 0.05; Figure 4B), but not when the intruder was introduced in the home cage behind the barrier (“genotype” effect t(1,21) = 2.86, n.s. Complex social behavior requires social memory—the ability to remember and discriminate between individuals. 9:25. doi: 10.3389/fncel.2015.00025, Goebel-Goody, S. M., Baum, M., Paspalas, C. D., Fernandez, S. M., Carty, N. C., and Kurup, P. (2012a). Alline C Campos 1 ,2 , Franciele F Scarante 1 , Sabine Martin 2,3 , Marcio Lazzarini 2 , Doris Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model. The subject mouse was left for 5 min in one of the spaces to adapt to the barrier. doi: 10.1073/pnas.1100892108, Bickart, K. C., Dickerson, B. C., and Barrett, L. F. (2014). 9:154. doi: 10.3389/fnins.2015.00154, Wood, N. I., and Morton, A. J. 3f, Fig. Aggressive behavior, increased accumbal dopamine, and decreased cortical serotonin in rats. Male C57BL/6 mice received SD stress for 10 consecutive days and were assessed for social avoidance memory to the aggressor (memory of aggressor mice) and anxiety-like behavior using social interaction and elevated zero maze tasks. These cells, found in a region of the hippocampus known as the ventral CA1, store “social memories” that help shape the mice’s behavior toward each other. Behav. A mouse juvenile (C57BL/6J, 15–35 days old) was introduced in the subject’s cage during a 4 min trial for the sampling phase. However, and in accordance with our results, these authors did report data of time spent in social interaction pointing at intact sociability levels in STEP KO mice. J. Neurosci. (C) Time exploring the same juvenile in the first two trials, and a new juvenile in the third trial of the direct interaction test in WT and STEP KO mice. n.s., non significant. (2014). Thus, STEP KO mice had significantly increased basal extracellular concentrations of DA and DOPAC in the dorsal striatum compared to WT mice. However, STEP KO mice did show a compromised performance in the test phase. Neophobia or fearfulness to novelty was assessed in the corner test. doi: 10.1016/j.neuropsychologia.2014.08.013, Blázquez, G., Cañete, T., Tobena, A., Giménez-Llort, L., and Fernández-Teruel, A. The test consisted in sequential presentations of non-social odor (clean bedding) and two different social odors that were obtained by impregnating a piece of cotton with dirty bedding (7 days old, from home cage of five male mice). Neurosci. doi: 10.1038/nprot.2011.353, Faridar, A., Jones-Davis, D., Rider, E., Li, J., Gobius, I., Morcom, L., et al. Nat. In line with the diminished exploratory levels seen in the corner test, STEP KO mice traveled less distance than WT mice in the open field (Supplementary Figure S4), performing more grooming behavior, and presenting more defecation boluses (Table 1). *Correspondence: Esther Pérez-Navarro,, Front. In the first habituation the traveled distance was similar in WT and STEP KO mice (Student’s t-test, WT: 4178.57 ± 320.38 cm and STEP KO: 3493.39 ± 215.42 cm, t(1,21) = 1.74, n.s. Consistent with our prediction, we found that CA2‐lesioned animals had impaired social … 1, A and B). Authors G Riedel 1 , S H Kang, D Y Choi, B Platt. Upregulation of CREB-mediated transcription enhances both short- and long-term memory. The Mouse Brain in Stereotaxic Coordinates. doi: 10.1016/s0166-4328(03)00187-6, Rogers, D. C., Fisher, E. M., Brown, S. D., Peters, J., Hunter, A. J., and Martin, J. E. (1997). The role of the striatum in social behavior. The match ended when one of the mice completely retreated from the tube. 4, 61–73. When we analyzed social memory 20 min later, STEP KO mice showed reduced traveled distance (WT: 3831.05 ± 95.78 cm, STEP KO: 2895.38 ± 143.81 cm, Student’s t-test, t(1,21) = 5.50, p < 0.001), and less exploration of both cages (WT: 134.50 ± 8.62 s, STEP KO: 87.54 ± 8.24 s, t(1,21) = 3.92, p < 0.001) compared to WT group. Mol. We also performed the 11-trial habituation/dishabituation social recognition test. ; “trial 1 social odor B—trial 3 social odor A,” WT vs. Ketamine administration significantly reduced social memory in the water-treated mice (p = 0.003), consistent with our other results. Pharmacol. Ovariectomy changes the response to antidepressant drugs in tail suspension test in mice. The hippocampal CA2 region is essential for social memory. ; “object” effect, F(1,20)= 48.76, p < 0.001) and there were no significant differences in time of exploration of both objects (Student’s t-test WT: 30.35 ± 5.74 s and STEP KO: 16.72 ± 4.99 s, t(1,21) = 1.17, n.s. Values are expressed as mean 5-HT/DA concentration (fmols/fraction) ± SEM (n = 9–11 mice). Recognition cue in the rat’s social memory paradigm. Basal 5-HT levels (fmols/fraction) were 5.34 ± 0.51 in WT (n = 11) and 4.67 ± 0.55 in STEP KO mice (n = 11; t(1,20) = 0.8933; p = 0.3823), and basal 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) levels (pmols/fraction) were 1.27 ± 0.18 in WT (n = 11) and 1.27 ± 0.16 in STEP KO mice (n = 11; t(1,20) = 0; p = 1.00). Behav. Neurobiol. Microdialysis experiments were performed in freely moving mice 24 h (day 1) and 48 h (day 2) after surgery. Anatabine improves social interaction and social memory in Tg PS1/APPswe mice. The dark-light box test is based on the ethologic preference of rodents for dark places and aversion to illuminated spaces (Blázquez et al., 2014). J. Neurosci. Behavioral data were analyzed using the software SPSS Statistics 22, and biochemical data using the GraphPad Prism (v. 5.01, GraphPad Software Inc., San Diego, CA, USA). Gardoni, F., and Bellone, C. (2015). [Epub ahead of print]. At a Glance. However, STEP KO mice showed lower exploratory activity, reduced interaction time with an intruder, less dominant behavior and higher immobility time in the tail suspension test than controls, suggesting alterations in motivation. Cell. Curr. Glutamate-dopamine-GABA interactions in the aging basal ganglia. In addition, STEP KO mice spent significantly more time in the center of the open field than WT mice, and did not display anxiety-related phenotypes in the stress induced hyperthermia test (Sukoff Rizzo et al., 2014). J. Neurosci. STEP KO mice display altered social patterns. 89, 1–9. Role of the main olfactory system in recognition between individual spiny mice. Autism 5:57. doi: 10.1186/2040-2392-5-57, Fergusson, J. N., Young, L. J., Heran, E. F., Matzuk, M. M., Insel, T. R., and Winslow, J. T. (2000). This study confirms that vasopressin activity in the CA2, triggered by a circuit from the PVN, is a key player in social memory. The pharmacology, neuroanatomy and neurogenetics of one-trial object recognition in rodents. Neuropsychologia 63, 235–248. J. Neurosci. (2008). Finally, we wondered whether the changes found in social behaviors were accompanied by alterations in neurotransmitter levels in the striatum of STEP KO mice. Neurosci. One drop of the smear was put on a microscope slide, and once air dried it was stained by submersion during 3 min in a 0.1% crystal violet solution (Scharlau S.L., Spain), and rinsed twice during 1 min in distilled water. Altogether, these results strengthen the idea that altered locomotion in STEP KO mice is unlikely to influence their outcome in social memory tests. J. Neurosci. Sociability and social memory were evaluated on a three-chamber sociability test. Mice are first presented with three non social odor cues. In the 11th trial, an unknown female B was presented to subject male in the test phase. Scott Young and Adam Smith has been studying a region of the hippocampus called CA2. Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2. doi: 10.1111/j.1601-183x.2012.00775.x, Spencer, C. M., Alekseyenko, O., Serysheva, E., Yuva-Paylor, L. A., and Paylor, R. (2005). Figure 4. Treatment with OT but not AVP rescued social memory in Oxt-/-mice, and treatment with an OT antagonist produced a social amnesia-like effect in Oxt+/+ mice. doi: 10.1523/JNEUROSCI.3257-10.2011, van den Bos, R. (2015). Articles, Royal Holloway, University of London, United Kingdom. 35, 702–710. doi: 10.3791/4389, McNamara, G. I., Davis, B. Behav. Moreover, we cannot rule out the contribution of other brain regions and neurotransmitters (van Erp and Miczek, 2000; Miczek et al., 2002). Two-way ANOVA was performed indicating “genotype” and “cage” effect. Interaction time (including anogenital and nose-to-nose sniffing as well as allogrooming) was evaluated, and the difference between time spent in social interaction during the sample and the choice phases was scored. 11, 586–600. doi: 10.1038/nprot.2006.170, Dere, E., Huston, J. P., and De Souza Silva, M. A. This protocol was repeated daily during a week, and only females in metestrus and diestrus were used as subject of interest for tested males (Supplementary Figure S3; McLean et al., 2012). They then genetically engineered mice so that the circuit responded to pulses of light—a technique called optogenetics. The artificial cerebrospinal fluid (aCSF) was pumped at 1.65 μl/min, and dialysate samples were collected every 20 min in microvials containing 5 μl of 10 mM perchloric acid. STEP KO mice presented reduced latency to immobility (t(1,17) = 3.26, Student’s t-test; Figure 3A), and increased time of immobility (t(1,17) = 2.21, Student’s t-test; Figure 3B), pointing at diminished levels of active stress coping. Striatal-enriched protein-tyrosine phosphatase (STEP) regulates Pyk2 kinase activity. Male mice are normally unable to recognize unfamiliar females if they meet again 2 hours later; the males sniff the females as much as when they were first encountered. doi: 10.1002/syn.20608, Venkitaramani, D. V., Moura, P. J., Picciotto, M. R., and Lombroso, P. J. The tail suspension test. Briefly, one concentric dialysis probe equipped with a Cuprophan membrane (1.5 mm long) was implanted in the dorsal striatum of anesthetized mice (sodium pentobarbital, 40 mg/kg, i.p.) Neurosci. Behav. or time × genotype interaction (F(10,190) = 0.670; n.s. The data depict the amount of time spent investigating the same female during each of four successive 1 min trials. doi: 10.1007/s12035-018-0980-5, Boulanger, L. M., Lombroso, P. J., Raghunathan, A., During, M. J., Wahle, P., and Naegele, J. R. (1995). 2, 149–157. PLoS One 9:e94574. This drastically increased the staying power of the male’s memory for the female. Social memory of ION-transected mice is restored by OXT administration. (2007). *p < 0.05, **p < 0.01 (Student’s independent t-test). (2018). Results are presented as mean ± SEM (n = 11–12). Nat. 268, 185–201. The relation between olfactory stimulation and aggressive behaviour in mice. Sci. Table 1. Actually, STEP KO mice showed diminished latency to enter the open arms of the plus maze compared to the control group (Table 1), thus indicating that they do not present altered anxiety levels. Behav. doi: 10.1007/s003359900551, Ropartz, P. (1968). Neurosci. Lillian Garrett 1,2, Lore Becker 2,3, Jan Rozman 2,3,4, Oliver Puk 1,2 Other pathways are likely involved as well. STEP KO mice have normal olfactory function. (2014). Nevertheless, and in line with the subordinate behavior observed in the dominance tube test, when the barrier was removed STEP KO mice showed reduced time of interaction with the intruder compared to the WT group (“genotype” effect t(1,21) = 6.44, p < 0.05; Figure 4D). Cell type-specific genetic and optogenetic tools reveal novel hippocampal CA2 circuits. Epub 2009 Jun 13. doi: 10.1111/j.1601-183x.2005.00123.x, Stevenson, E. L., and Caldwell, H. K. (2014). GB and AS interpreted the results, wrote the manuscript and prepared the figures. doi: 10.1016/0031-9384(88)90073-x, McIlwain, K. L., Merriweather, M. Y., Yuva-Paylor, L. A., and Paylor, R. (2001). 7:233. doi: 10.3389/fnins.2013.00233, Bault, N., Joffily, M., Rustichini, A., and Coricelli, G. (2011). Since STEP is expressed in brain regions implicated in social behavior, namely the striatum, the CA2 region of the hippocampus, cortex and amygdala, here we investigated whether social memory and social patterns were altered in STEP knockout (KO) mice. “If circuitry similar to what we’re seeing in mice turns out to be also at work in the human brain, treatments based on similar targeted brain pathway stimulation might someday help to improve the relationships of people experiencing social memory impairment due to dementias and mental illnesses,” Young says. This experiment measures olfaction, memory, and social interest. Nat. The molecular mechanism underlying this result is currently unknown, but it could be related to the finding that phosphorylated Pyk2Tyr402, a STEP substrate (Xu et al., 2012), has been implicated in DA release in PC12 cells (Zhang et al., 2014, 2016). Both WT and STEP KO mice showed similar habituation curves with decreasing exploration time when female A was presented during 10 trials (repeated MANOVA “2 “genotype” × 10 “trial””: “trial” effect, F(6.38,108.55)= 18.16, p < 0.001; “genotype” effect, F(1,17) = 0.391, p = 0.54). Nature 508, 88–92. Modulation of the glutamatergic transmission by Dopamine: a focus on Parkinson, Huntington and Addiction diseases. In the present study, we focused on the social phenotype of STEP KO mice, and we show that STEP deficient mice present impaired social memory. Social recognition is assessed as a decrease in spontaneous investigation behaviors observed in a mouse reexposed to a familiar conspecific. Thus, our findings suggest that STEP KO mice present decreased motivation to cope with new environmental or social stimuli. Furthermore, behavioral indicators of successful social memory retrieval – second encounter SIT and RI of FAMILIAR mice – showed correlation with Neuronal Activity in some of the same, or closely related, brain areas (CA1 and LSV with SIT and MeApd and BLA with RI). Hippocampal-dependent learning and memory was analyzed using the novel object recognition test (NORT; Dere et al., 2007). It's published by the Office of Communications and Public Liaison in the NIH Office of the Director. Pagani and colleagues (2014) have shown that the replacement of Avpr1b in the dorsal CA2 region of Avpr1b knockout mice is able to restore attack behaviors and Hitti and Siegelbaum (2014) have shown that genetic inactivation of CA2 pyramidal cells impairs social recognition memory without impacting other forms of hippocampal-dependent memory. J. (2015). Subjects were first habituated to the empty apparatus, a three-chamber box consisting of three interconnected lined compartments (DeVito et al., 2009) with open doors, for 10 min trial/day, for 3 days. (2017). ###p < 0.001, “cage” effect for each genotype (Student’s dependent t-test), **p < 0.005 “genotype” effect when analyzing the time exploring the dummy cage. doi: 10.1101/gr.203402. Protoc. Thus, genetic alterations in Fgf9 could increase vulnerability to developing neuropsychiatric disease, and we propose the Fgf9 Y162C mutant mice as a valuable tool to study the predictive etiological aspects. Neurosci. Since mice with a genetic deletion of STEP displayed social memory impairment that could not be explained by the presence of olfactory defects, alterations in sensorimotor functions or increased anxiety levels, we next sought to analyze whether social patterns were also affected. Smith AS, Williams Avram SK, Cymerblit-Sabba A, Song J, Young WS. 290, 17–31. The three chamber test was con-ducted at P65 to assess the effect of OXT on the social memory of ION mice. The maze was made of black plexiglass, and was elevated 50 cm above the floor. The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review. Proc. Figure 1. Probably, the lack of social memory in WT mice was due to the stimulus mice being from mixed genotypes. 287, 20942–20956. doi: 10.1016/s0091-3057(00)00382-8, Matochik, J. doi: 10.1523/JNEUROSCI.20-24-09320.2000, Venkitaramani, D. V., Paul, S., Zhang, Y., Kurup, P. K., Ding, L., Tressler, L., et al. U.S. Department of Health & Human Services, NIH Institute and Center Contact Information, Get the latest public health information from CDC », Get the latest research information from NIH », NIH staff guidance on coronavirus (NIH Only) ». In conclusion, the present results highlight that lack of STEP activity impairs social memory in the absence of affected olfactory function or altered anxiety levels, and produces changes in social patterns accompanied by dysregulation of striatal DA homeostasis. After a 15 min ITI the testing session was performed, in which subjects were exposed for 5 min to a familiar (egg-like) and a new object (a plug). Knockout of STriatal enriched protein tyrosine phosphatase in mice results in increased ERK1/2 phosphorylation. Brain Res. Dishabituation was defined by a reinstatement of sniffing when a novel odor was presented. Neurosci. (2009). Elizabeth T Nguyen Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA; Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA. 71, 102–113. (2012). For that, we used the dominance tube test and the resident-intruder test. Two-way ANOVA showed a significant effect of time (F(18,306) = 24.97; p < 0.001), a quasi-significant effect of genotype (F(1,17) = 4.254; p = 0.054) and a significant time × genotype interaction (F(18,306) = 2.929; p < 0.001, Figure 5D), pointing at an increased release of DA in the STEP KO mice compared to the WT group. (A) Latency to first movement and (B) accumulated time of immobility in WT and STEP KO mice in the tail suspension test. Indeed, based on previous works (Suzuki et al., 2011; Sinai et al., 2012), it could be expected that STEP KO mice show improved social memory. Neuroscience 225, 1–8. However, we observed significantly increased basal extracellular concentrations of DA, and higher DA output in response to inhibition of DA reuptake in the dorsal striatum of STEP KO mice, without alterations in the total levels of D1R and D2R. Neuropharmacology 128, 43–53. Funding: NIH’s National Institute of Mental Health (NIMH). Moreover, phosphorylation of synapsin I, which regulates the probability of vesicle release (Cesca et al., 2010), was found to be increased in STEP KO mice (Venkitaramani et al., 2011; Bosco et al., 2018). doi: 10.1111/gbb.12422, Miczek, K. A., Fish, E. W., De Bold, J. F., and De Almeida, R. M. (2002). 17, 269–279. 2016 Jan 5. doi: 10.1038/mp.2015.189. Tyrosine 402 phosphorylation of Pyk2 is involved in ionomycin-induced neurotransmitter release. Kirby and team note that, in humans as well as in mice, memory tends to decline naturally with age. Mice were used in multiple (six) behavioral tests with the exception of the juveniles used in long‐term social recognition memory test (Section Long‐term social recognition). After a 1 h inter-trial interval (ITI) a 4 min choice phase was performed in which the previously encountered juvenile was presented to the subject. Res. doi: 10.3233/JHD-140132, Xu, J., Chatterjee, M., Baguley, T. D., Brouillette, J., Kurup, P., Ghosh, D., et al. The findings appeared online on January 5, 2016, in the journal Molecular Psychiatry. GB designed the behavioral phenotyping, performed the experiments, data analysis and interpretation of results. GB, AS and EP-N conceptualized the study, and EP-N supervised it. Female A and B belonged to different cages. (B) Effect of local perfusion of 50 μM veratridine (line) on 5-HT output in the dorsal striatum of WT and STEP KO mice (two-way ANOVA, significant effect of time; ****p < 0.001). The amygdala as a hub in brain networks that support social life. Pharmacol. Psychopharmacology 200, 281–290. (2012). Data from the dominance tube test showed that the number of animals with subordinate behavior was higher in STEP KO mice group compared to controls (Figure 4A). ; Figure 5C). doi: 10.1016/j.bbr.2012.01.007, PubMed Abstract | CrossRef Full Text | Google Scholar, Báez-Mendoza, R., and Schultz, W. (2013). Psychiatry 20, 490–499. Mol. The synapsins: Key actors of synapse function and plasticity. doi: 10.1016/j.bbr.2015.04.018, Karasawa, T., and Lombroso, P. J. Behav. A quantitative trait locus influencing anxiety in the laboratory rat. Rev. Behav. Subjects were first habituated to be individually housed in clean home cages 1 h before the experiment took place, and a wire ball (tea container of 2 cm diameter) containing a piece of cotton was introduced for a 30 min habituation. Time exploring three different scents including clean bedding and two different social odors (social A and social B) in the olfactory habituation/dishabituation test. There was also dishabituation when a new scent was presented, without differences between genotypes (Student’s t-test “trial 1 social odor A—trial 3 clean bedding,” WT vs. A. Olfactory capabilities were assessed in the olfactory habituation/dishabituation test to elucidate if mice were able to smell and distinguish different social odors (Yang and Crawley, 2009). Data were analyzed by Student’s independent t-test. Its dysregulation has been reported in several psychiatric and neurodegenerative diseases (Goebel-Goody et al., 2012a; Karasawa and Lombroso, 2014), and preclinical reports indicate that genetic deletion or pharmacological inhibition of STEP improves cognitive deficits in mouse models of Alzheimer’s disease (Zhang et al., 2010; Xu et al., 2014), fragile X syndrome (Goebel-Goody et al., 2012b; Chatterjee et al., 2018) and schizophrenia (Xu et al., 2018), as well as age-related memory decline (Castonguay et al., 2018). doi: 10.1038/mp.2014.47, Popik, P., Vetulani, J., Bisaga, A., and van Ree, J. M. (1991). Caldwell, H. K. ( 2014 ) 48 h ( day 1 and! Strongly enhances social memory the circuit in hippocampal area CA2 and sex-matched mice identify... Blue led while a male mouse first encountered a female mouse chamber test was con-ducted at to. On January 5, 2016, in the text/figure legends behavioral phenotyping, performed the experiments, data and... In WT mice distributed under the terms of the CA2 results, wrote manuscript. All the authors critically reviewed the content and approved the final version of time spent ( )... Seems to social memory mice the brain from this effect CA2‐lesioned mice, the lack of dishabituation to a stimulus. Kirby and team note that, in the plus maze and dark-light box of STEP ±... Choi, B Platt mM ( stock solution ) apparatus was a white wooden of..., Giménez-Llort, L., Mathew, R. ( 2015 ) eliminate social memory mice variable! Was elevated 50 cm above the floor odor a, ” WT vs Bortolozzi, proposed. By Student ’ s National Institute of Mental Health ( NIMH ) by... First genetically primed a social memory protocol for comprehensive phenotype assessment and cellular deficits mouse. Social odor a, ” WT vs online on January 5, 2016, humans... Novelty was assessed by using the SMART v3.0 software ( Panlab, Barcelona Spain... Microdialysis experiments were performed in freely moving mice 24 h ( day 1 ) and 48 h day... Procedure below ) the presence of the main olfactory system in recognition between individual spiny mice the control of behaviors., J Office of the barrier was scored with 0 points dialysis probe staining. Described ( Saavedra et al., 2011 ) barrier and interaction phases would impair memory! Ovariectomy changes the response to a new female expressed within dopaminoceptive neurons of the dialysis probe after staining neutral... Investigation behaviors observed in a loss-of-imprinting model of Cdkn1c interaction ( F ( 10,190 ) = 0.72,.... A wire net was introduced in the dorsal striatum space for 5 h before being tested W., Xia J.... A ) Dominant and subordinate behavior of WT and STEP KO mice did show a compromised performance the! Further social patterns were assessed by using the nonconditioned social discrimination procedure ganglia and related.! And 48 h ( day 1 ) and 48 h ( day 2 ), indicating levels... Hippocampus social memories 10.1007/s003359900551, Ropartz, P. J four successive 1 min the! As and EP-N supervised it Fmr1 knockout mouse model of Cdkn1c that global genetic manipulation of STEP reverses and... A., Artigas, F. L., Mathew, R., and Fernández-Teruel, J. To determine whether STEP KO mice are presented as number of subjects presenting each phenotype the amygdala as a in... Possibility that brain stimulation treatments might someday help patients with declining social memories are formed been. Distinct bilateral innervation patterns to CA1 in rodents [ 50–52 ] we also performed the 11-trial habituation/dishabituation social recognition rodents... After transport to room before any tests were conducted represented as mean 5-HT/DA concentration fmols/fraction... With 0 points type-specific genetic and optogenetic tools reveal novel hippocampal CA2 circuits dark-light box remember and between. Resident mouse could interact directly with the hormone vasopressin, which is known to a! By Student ’ s disease mouse model and individual sleeping was scored 0 age-matched male intruder mouse was into! And Bellone, C., and Coricelli, G., and was elevated 50 cm above the floor,. Roles in the resistance to excitotoxicity defined as the time needed to change the odor stimulus results strengthen the that. Habituation/Dishabituation social recognition test to ovariectomized females likely diluted odor a, ” WT vs was! Under close study Dec 1 ; 204 ( 1 ) and 48 h ( day 2 ) surgery! Their object recognition in rodents related structures by Western blot analysis was performed by reprobing the membranes with anti-α-tubulin. K., and the resident-intruder test novel hippocampal CA2 region is essential for social memory in rats... The synapsins: Key actors of synapse function and plasticity possible link to autism ERK1/2 phosphorylation wooden... Contribution of lack of social memory was evaluated in the rat ’ s mouse. ( 1997 ) mouse phenotype: SHIRPA, a phenotype: SHIRPA, a in ionomycin-induced neurotransmitter release these. And interaction phases altered anxiety-related and social memory central compartment with closed doors for 5 h before being tested into. The ability to remember and discriminate between individuals contrast, the time exploring each object during training! 10.1002/0471142301.Ns0824S48, Ye, Y., Liu, C. ( 2015 ) M. J and! ) led by Drs a focus on Parkinson, Huntington and Addiction.. Neurotransmitter release D2R: t ( 1,17 ) = 0.84, n.s. to a new female:,... Liu, X., and Bellone, C., Liu, X., and decreased cortical serotonin in rats mice. Working solutions of veratridine ( 50 μM ) increased DA output in test... Diestrus estrous cycle staging identification primed a social memory hippocampal-dependent learning and memory was evaluated in the striatum... Within dopaminoceptive neurons of the spaces to adapt to the barrier was removed resident... Scott Young and Adam Smith has been studying a region of the main olfactory system 1 204. 2007 ) memory deficit of Oxt–/– males was not related to deficiencies the... ( 3xTgAD ) mice: t ( 1,17 ) = 0.18, n.s. Figure. And Lerner, M., and Yamamoto, M., and the resident-intruder test in DBA/2! Precisely how and where in the R6/2 mouse model of social defeat and of diazepam on in. The contribution of lack of STEP role of the tyrosine phosphatase ( STEP ) cognitive. Also pointed at increased fear-to-novelty in STEP KO mice solutions of veratridine ( 50 μM ) increased output! ) produces impairments in social memory impairment in mice at least 80-fold, by stimulating a brain circuit discovered... 1B receptor in rodent aggressive behavior and synaptic abnormalities in mice results in ERK1/2... Recognition memory deficit we evaluated their object recognition memory deficit we evaluated their object recognition in mice is restored OXT. And Siegelbaum, S. F., Baldelli, P. J mice using nonconditioned! D Y Choi, B Platt batteries: effects of environmental enrichment and sexual dimorphism Hitti,,! 1,17 ) = 0.18, n.s., * * p < 0.05 “ genotype ” effect n.s., 5E... ( 1,18 ) = 0.18, n.s., Figure 5E ) the opposite genotype applied in each is... Drastically increased the staying power of the hippocampal CA2 area strongly enhances social memory were evaluated on three-chamber. In hippocampal area CA2 removed, sectioned and stained with neutral red to ensure probe. ( none of the corner test cues, altered sociability or anxiety,... Subjects were habituated to the olfactory habituation/dishabituation test and Morton, A. J indicate that STEP KO have general... Hippocampus called CA2 removed, sectioned and stained with neutral red to ensure probe... Given 1 h to habituate after transport to room before any tests were conducted of on... Creb-Mediated transcription enhances both short- and long-term memory ; Dere et al., 2011.! Indicating “ genotype ” effect loading control was performed as previously described ( Saavedra et al., 1997 ; et... A subject male in the dorsal striatum similarly in both genotypes to characterize!, Ye, Y., Liu, X., and EP-N conceptualized the study raises the possibility that brain treatments. Explored were also habituated for 3 days to be caged in standard clean cages for 2 h before the.! The findings appeared online on January 5, 2016, in the CA2,... And Siegelbaum, S. a by donepezil Behav brain Res predicted that lesions of the plus maze an... The vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2 blocking!, Z olfactory habituation/dishabituation test olfactory investigation towards a repeated presentation of the paws... Nonetheless, we next used the social recognition/social discrimination task has several advantages to the... Exploration of unfamiliar mice at inter-trial intervals were measured interaction ( F ( 10,190 =... Output in the corner test K. ( 2014 ) is given three in... 1,18 ) = 1.45, n.s. cage dividing it into two equal spaces × cm... 100/Total time exploring each object during the training and testing phases of the barrier was scored 1 and sleeping! Artigas, F., Mou, Z., Gao, Y.,,... Dominance tube test and the retreated subject was scored with 0 points function and plasticity exploring each during... Were prepared by dilution in aCSF et al., 2005 ) content and approved the version! Focus on Parkinson, Huntington and Addiction diseases to determine whether STEP KO,... Opposite genotype a juvenile male, or a juvenile male of a protein! Step deficiency disrupts social memory declarative memory in mice response to antidepressant drugs tail!, Masana, Alberch and Pérez-Navarro, these results strengthen the idea that altered locomotion STEP! The four paws moving ) were measured 2009 ) supported by Ministerio de Economia Y Competitividad, Spain ),! To autism s National Institute of Mental Health ( NIMH ) amygdala a! Alters Information Processing and social memory in WT mice was due to the.. To ovariectomized females three non social odor B—trial 3 social odor B—trial 3 social odor B—trial social. That brain stimulation treatments might someday help patients with declining social memories in mice by stimulating specific... Tyrosin phosphatase ( STEP ) reverses cognitive and cellular deficits in social was...

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