Oral Session

Oral Session 6 一般口演6

O6-1 Estimation of depression-like behaviors using a test battery in drug-induced model of common marmosets マーモセットの薬物惹起性モデルにおけるテストバッテリーを用いたうつ様行動の評価 Yamanaka Hajime（山中創）¹，石橋英俊²，高田昌彦¹，中村克樹³ ¹Systems Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Japan ²Pre-clinical Research Center, Tokyo Medical University, Tokyo, Japan ³Cognitive Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Japan Depression is a serious mood disorder with a high prevalence. Although research works on depression have so far been performed mainly in rodents, the use of nonhuman primates is considered to improve the efficiency of assessing the similarity of depressive symptoms, termed face validity. Common marmosets have increasingly been utilized in recent years as potential models of neurological/psychiatric disorders. Since diagnostic criteria for psychiatric disorders are primarily based on altered behavioral types, the development of an appropriate test battery is critical to assess depression-like behaviors. In this study, several behavioral tests were executed to validate their utility in marmosets. Then, a battery of six tests were established through repeated measurements over several days in a reserpine-induced depression model. First, a peephole test was developed to examine visual exploratory behavior (VEB) that is frequently discussed in terms of motivation, curiosity, and interest. We found that conspecific individuals used as presentation stimulus effectively induced VEB. Second, a sucrose preference test was applied for investigating anhedonic behavior. In this test, a sucrose concentration-response curve was generated to reveal that 1.8% sucrose was optimal in marmosets. The reserpine-induced response patterns were tested using a battery with four more tests including food intake. Of the nine marmosets, one was identified to exhibit typical response patterns. The incidence rate (11%) in our study was nearly equivalent to the clinical incidence rate (18%) for depressive patients with reserpine treatment. Thus, the present test battery might have a potential to assess the face validity of depression-like behaviors in primate models.		O6-2 Prefrontal Parvalbumin Interneurons are Essential for Social Behavior Development 前頭前皮質Parvalbumin interneuronの社会性行動への関わり Yamamuro Kazuhiko（山室和彦）^1,2,3,4,5,6，Lucy K Bicks^2,3,4,5,6，Roger L Clem^3,6，Scott J Russo^3,6，Schahram Akbarian^2,3,6，森下博文^2,3,4,5,6 ¹Department of Psychiatry, Nara Medical University, Nara, Japan ²Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA ³Department of Neuroscienc, Icahn School of Medicine at Mount Sinai, New York, USA ⁴Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, USA ⁵Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, USA ⁶Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, USA Social isolation (incl. ‘loneliness’ experience) during developmental critical windows could be highly detrimental to proper functioning of mature prefrontal cortex (PFC) and establishment of appropriate adult behaviors. However, the specific circuits that undergo social experience-dependent maturation to regulate social behavior development are poorly understood. Here we show that juvenile social isolation in mice leads to reduced intrinsic excitability and input drives of adult parvalbumin-positive interneurons (PVIs) in medial PFC (mPFC), suggesting juvenile social experience is required for their proper activation in adulthood. In vivo imaging of mPFC-PVI activity by fiber photometry demonstrated that adult mPFC-PVIs are preferentially activated by social signals. Recapitulating decreased activity of PVIs through acute chemogenetic suppression revealed that normal social behavior requires physiological mPFC-PVI activity. Conversely, chemogenetic restoration of mPFC-PVIs activity in the adult animal rescued juvenile isolation-induced social deficits. Therefore, PVI development in the juvenile mPFC is critically linked to long-term impacts on social behavior.

O6-3 Repulsive axon guidance molecule FLRT2 regulates social behavior 神経軸索ガイダンス分子FLRT2による社会性行動制御 Yamagishi Satoru（山岸覚）¹，篠田陽²，小川修平³，宮川剛⁴，高雄啓三⁵，佐藤康二¹ ¹Dept of Organ & Tissue Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan ²Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan ³Division of Experimental Animal Immunology, Tokyo University of Science, Tokyo, Japan ⁴Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan ⁵Life Science Research Center, University of Toyama, Toyama, Japan During cortical development, migrating neurons and pathfinding axons are guided by molecular cues within the extracellular matrix or on the surface of ambient cells. These cues are interpreted as attractive or repulsive, depending on the set of receptors and signal transducers the cell expresses. We previously identified fibronectin leucine-rich transmembrane protein (FLRT) family as ligand of Unc5 proteins, a well-known Netrin receptors. FLRT2 is expressed in the cortical plate (CP) and inhibited migration of Unc5D+ cells in the subventricular zone (SVZ). The upper layer neurons in FLRT2 mutant mice showed earlier migration to CP, indicating repulsive function of FLRT2. However, the behavioral phenotype of FLRT2 deficient mutant mice was unclear. Here, we comprehensively analyzed behaviors of Emx1 cre induced-FLRT2 conditional knock-out mice using the test battery. We found that mutant mice showed significant enhancement of anxiety-like behaviors (light/dark transition and elevated maze), pain sensitivity (hot plate) and social interaction. Furthermore, exploratory locomotor activity was decreased (open-field and Y-maze tests). Next, we electrophysiologically assessed synaptic transmission in the mutant mice such as LTP and paired pulse facilitation using hippocampal acute slice. However, we could not find any significant difference. Furthermore, we analyzed the morphological change in primary cultured neurons. Interestingly, neurons from FLRT2 mutant harbored longer axons. These results suggest that mis-migrated/mis-connecting neurons might affect the behaviors of FLRT2 deficient mice such as social interaction and anxiety-like behaviors.