Association of serum sodium levels with fractures and mortality in patients undergoing maintenance hemodialysis.

BACKGROUND: Hyponatremia is implicated in pathological bone resorption and has been identified as a risk factor for bone fracture in the general population. However, there are limited data on the association between serum sodium levels and fracture risk in patients undergoing hemodialysis (HD). METHODS: We analyzed a historical cohort of 2220 maintenance HD patients to examine the association between serum sodium levels and the risk of fracture and mortality. We also examined the association between serum sodium levels and osteoporosis, based on metacarpal bone mineral density, in a subcohort of 455 patients with available data. In addition, we examined the association between serum sodium levels and bone turnover markers in a separate cross-sectional cohort of 654 maintenance HD patients. RESULTS: During a median follow-up of 5.4 years, 712 patients died, 113 experienced clinical fractures, and 64 experienced asymptomatic vertebral fractures. Lower serum sodium levels were associated with an increased risk of mortality (HR 1.06 per 1 mEq/L decrease; 95% CI 1.03-1.09) but not with the risk of clinical fracture (HR 1.04 per 1 mEq/L decrease; 95% CI 0.97-1.11). A similar lack of association was observed for asymptomatic vertebral fracture and any fracture. Serum sodium levels were also not associated with osteoporosis in a subcohort with available data (n = 455) or with bone alkaline phosphatase or tartrate-resistant acid phosphatase-5b in a separate cross-sectional cohort. CONCLUSION: Serum sodium levels were associated with mortality but not with fracture risk, osteoporosis, or bone turnover markers in maintenance HD patients.

Record of Cryptosporidium serpentis from Goniurosaurus kuroiwae sengokui (Reptilia, Squamata, Eublepharidae) in Tokashikijima, Okinawa Prefecture, Japan.

In reptiles, infection with Cryptosporidium parasite can be lethal, especially in species of family Eublepharidae such as Eublepharis macularius and Goniurosaurus splendes species. We investigated the presence of Cryptosporidium spp. in wild reptiles, especially Goniurosaurus spp., in five islands of Japan. Nested PCR was performed to detect Cryptosporidium spp. in 38 fecal samples of 9 reptile species from five islands of Japan, and 3 (3/8) positive samples of Goniurosaurus kuroiwae sengokui from Tokashikijima, Okinawa Prefecture were detected. A BLAST search of the detected gene sequences revealed that the all 3 samples were identified as Cryptosporidium serpentis, a reptile-specific Cryptosporidium parasite. This is the first record of Cryptosporidium from a wild Goniurosaurus species in Japan and worldwide.

Usefulness of a Novel Vascular Access Management Method Using a Laser Blood Flowmeter.

INTRODUCTION: Various methods for vascular access (VA) management have been studied. We investigated the usefulness of a new, simple, and quantitative VA management method using the Pocket LDF® laser blood flowmeter (hereinafter "LDF") that noninvasively measures peripheral circulation flow. METHODS: Peripheral circulation flow was measured in 82 patients (43 men) on maintenance hemodialysis with an arteriovenous fistula (AVF). The shunt symmetry index (SSI) was calculated as peripheral circulation flow in the AVF limb divided by that in the non-AVF limb. SSI was used for microcirculation evaluation and also compared by AVF site. Patients undergoing vascular access interventional therapy (VAIVT) underwent ultrasound evaluation (Doppler ultrasonography) of the AVF and SSI measurement before and after VAIVT. SSI was compared between those who did and did not require VAIVT, and the cutoff value for SSI was determined by receiver operating characteristic curve (ROC) analysis. RESULTS: As many as 86% of the patients who were measured peripheral circulation flow had SSI <1.0, which indicates that AVF reduced peripheral circulation flow. All patients who underwent VAIVT showed a decrease in SSI to <1.0 after VAIVT, probably due to improvement of stenosis. SSI differed significantly between patients who did and did not require VAIVT (1.20 ± 0.49 vs. 0.65 ± 0.33, p < 0.001), which indicates that SSI is affected by the presence of stenosis in the proximal vein of the VA anastomosis. In patients with SSI ≥1.0, stenosis of the proximal vein of the AVF caused stasis of blood flow, resulting in increased peripheral blood flow. AVF site seems to have no impact on peripheral circulation flow. The SSI cutoff value for the screening of proximal vein stenosis was 1.06 (sensitivity: 0.69, specificity: 0.93, area under the curve: 0.81). CONCLUSION: Based on the ROC analysis, we recommend considering AVF ultrasound for SSI >1.06. Our results suggest the usefulness of the described VA management method using the LDF.

Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients.

Two-thirds of urate is excreted via the renal pathway and the remaining one-third via the extra-renal pathway, the latter mainly via the intestine in healthy individuals. ABCG2, a urate exporter, is expressed in various tissues including the kidney and intestine, and its dysfunction leads to hyperuricemia and gout. ABCG2 is regarded as being responsible for most of the extra-renal urate excretion. However, the extra-renal urate excretion capacity via ABCG2 remains undefined in end-stage kidney diseases. Therefore, we evaluated the capacity of extra-renal ABCG2 using 123 anuric hemodialysis patients whose urate excretion depended on only the extra-renal pathway. ABCG2 function in each participant was estimated based on ABCG2 dysfunctional variants. We computed the uric acid pool (PoolUA) from bodyweight and serum urate level (SUA) using previously reported radio-isotopic data, and we analyzed the association between ABCG2 function and the PoolUA. SUA and PoolUA increased significantly with ABCG2 dysfunction, and extra-renal ABCG2 could excrete up to approximately 60% of the daily uric acid turnover in hemodialysis patients. Our findings indicate that the extra-renal urate excretion capacity can expand with renal function decline and highlight that the extra-renal pathway is particularly important in the uric acid homeostasis for patients with renal dysfunction.

Molecular mechanisms underlying activity-dependent ischemic tolerance in the brain.

Ischemic stroke is one of the leading causes of death and disability worldwide. The inhibition of cerebral blood flow triggers intertwined pathological events, resulting in cell death and loss of brain function. Interestingly, animals pre-exposed to short-term ischemia can tolerate subsequent severe ischemia. This phenomenon is called ischemic tolerance and is also triggered by other noxious stimuli. However, whether short-term exposure to non-noxious stimuli can induce ischemic tolerance remains unknown. Recently, we found that pre-exposing mice to an enriched environment for 40 min is sufficient to facilitate cell survival after a subsequent stroke. The neuroprotective process depends on the neuronal activity soon before stroke, of which the activity-dependent transcription factor Npas4 is essential. Excessive Ca2+ influx triggers Npas4 expression in ischemic neurons, leading to the activation of neuroprotective programs. Pre-induction of Npas4 in the normal brain effectively supports cell survival after stroke. Furthermore, our study revealed that Npas4 regulates L-type voltage-gated Ca2+ channels through expression of the small Ras-like GTPase Gem in ischemic neurons. Ischemic tolerance is a good model for understanding how to promote neuroprotective mechanisms in the normal and injured brain. Here, we highlight activity-dependent ischemic tolerance and discuss its role in promoting neuroprotection against stroke.

Serum Sclerostin Levels and Mortality in Hemodialysis Patients: An 8-Year Prospective Study.

INTRODUCTION: Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure. Sclerostin might be involved in the pathogenesis of vascular calcification, but few studies have examined the association between sclerostin and mortality in hemodialysis patients. METHODS: We analyzed a prospective cohort of 654 patients undergoing maintenance hemodialysis. The primary exposure variable was the baseline serum sclerostin level measured at study enrollment. The primary outcome was 8-year all-cause mortality. Mortality risk was assessed using Cox regression models adjusted for potential confounders. RESULTS: During a median follow-up of 7.6 years (interquartile range, 4.1-8.0 years), 229 of the 654 participants died. In a univariate analysis, serum sclerostin levels were not associated with mortality (HR per doubling, 0.94; 95% CI, 0.76-1.17). This result was unchanged after adjustment for age, sex, dialysis vintage, diabetes, prior cardiovascular disease, and body mass index (HR per doubling, 0.92; 95% CI, 0.72-1.17). Similar results were obtained for cardiovascular mortality. CONCLUSION: Serum sclerostin levels were not associated with mortality in maintenance hemodialysis patients. Further research is required to determine the role of sclerostin in vascular calcification and cardiovascular disease in kidney failure.

Formation of N-acyl-phosphatidylethanolamines by cytosolic phospholipase A2ε in an ex vivo murine model of brain ischemia.

N-Acyl-phosphatidylethanolamines (NAPEs), a minor class of membrane glycerophospholipids, accumulate along with their bioactive metabolites, N-acylethanolamines (NAEs) during ischemia. NAPEs can be formed through N-acylation of phosphatidylethanolamine by cytosolic phospholipase A2ε (cPLA2ε, also known as PLA2G4E) or members of the phospholipase A and acyltransferase (PLAAT) family. However, the enzyme responsible for the NAPE production in brain ischemia has not yet been clarified. Here, we investigated a possible role of cPLA2ε using cPLA2ε-deficient (Pla2g4e-/-) mice. As analyzed with brain homogenates of wild-type mice, the age dependency of Ca2+-dependent NAPE-forming activity showed a bell-shape pattern being the highest at the first week of postnatal life, and the activity was completely abolished in Pla2g4e-/- mice. However, liquid chromatography-tandem mass spectrometry revealed that the NAPE levels of normal brain were similar between wild-type and Pla2g4e-/- mice. In contrast, post-mortal accumulations of NAPEs and most species of NAEs were only observed in decapitated brains of wild-type mice. These results suggested that cPLA2ε is responsible for Ca2+-dependent formation of NAPEs in the brain as well as the accumulation of NAPEs and NAEs during ischemia, while other enzyme(s) appeared to be involved in the maintenance of basal NAPE levels.

Prediction of Service Performance Based on Physical Strength in Elite Junior Tennis Players.

In tennis, service requires a variety of complicated movements. Given the importance of taking the initiative to obtain points in a tennis match, it is crucial to make full use of speed and spin rate of service. Generally, a service that requires a higher spin rate would slow down, and a service that has increased speed would have a decreased spin rate. For players who are disadvantaged in height, although controlling spin rate is essential, slowing down service speed should be avoided. For these players, the challenge of service is to improve the speed without decreasing the spin rate. Players must also be trained to build physical strength required for this skill. It is not uncommon to work on physical training without a racket; however, few studies have reported on the effects of cultivated physical strength on on-court tennis performance. Therefore, this study aimed to propose physical measurements that could be used as indices to improve service performance in 58 elite Japanese junior male players. To test service performance, we used TrackMan tennis radar device to assess speed, spin rate, impact height, and impact depth. To test physical strength, we measured 5- and 20-m sprint, broad jump, medicine ball throw (forward, backward). We used a significant multiple regression equation to predict the first service speed obtained from the broad jump and the Medicine ball throw (backward). Additionally, a strong correlation was obtained between the predicted and measured values. In addition to physical strength, we suggest that the depth of the impact point (taking the hitting point forward toward the net) is important for improving the first service speed. However, we were not able to identify the physical strength test items that improve service spin rate. Other item should be examined in the future to determine the physical strength associated with spin rate. This result could help connect physical training and service performance.

Interrelationships Between Sclerostin, Secondary Hyperparathyroidism, and Bone Metabolism in Patients on Hemodialysis.

CONTEXT: Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure, but its role in the pathogenesis of renal bone disease remains unknown. OBJECTIVE: We aimed to explore the association of serum sclerostin with bone metabolism in patients undergoing hemodialysis, with a particular focus on parathyroid hormone (PTH)-dependent and PTH-independent pathways. METHODS: This cross-sectional and prospective cohort study included 654 patients undergoing hemodialysis at 10 facilities in Japan. We employed multivariable linear regression to explore whether sclerostin levels were associated with metacarpal bone mineral density (BMD), intact PTH, bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase-5b (TRACP-5b). We employed mediation analyses to explore whether and to what extent the association of PTH with bone turnover markers is mediated by sclerostin. We also compared sclerostin levels between patients with and without previous or incident fractures. RESULTS: The median sclerostin level in hemodialysis patients was 3- to 4-fold higher than that in healthy individuals. Higher sclerostin levels were associated with higher metacarpal BMD and lower levels of intact PTH, BAP, and TRACP-5b. However, the relationships of sclerostin with bone turnover markers were substantially attenuated after adjustment for PTH. Mediation analysis suggested that the effects of PTH on bone turnover markers were mainly direct rather than mediated by sclerostin. Sclerostin levels were not associated with previous or incident fractures. CONCLUSION: These findings suggest that in patients undergoing dialysis, sclerostin has only a limited role in bone metabolism and may not mediate the effect of PTH on bone turnover.

Ascending spinal tract formation in chick embryo originating from different spinal regions.

The present study aimed to assess spinal tract formation in neurons originating from cervical (C7), brachial (C14), and thoracic (T4) regions, with the lumbar (LS2) region as a reference, in a chick embryo. For the assessment of the spinal tracts, we introduced a vector expressing human placental alkaline phosphatase into progenitor cells generated after neural tube closure and belonging to the above segments, using in ovo electroporation. The ascending axons took primarily similar paths: dorsal commissural, ventral commissural, and dorsal non-commissural paths, with some variance depending on their originating segments. Some populations of non-commissural neurons later extended their axons following a ventral path. The elongation rates of these axons are primarily constant and tended to increase over time; however, some variations depending on the originating segments were also observed. Some of the dorsally ascending axons entered into the developing cerebellum, and spinocerebellar neurons originating from T4 projected their axons into the cortex of the cerebellum differently from those from LS2. These results unveil an overall picture of early ascending spinal tract formation.

Ras-like Gem GTPase induced by Npas4 promotes activity-dependent neuronal tolerance for ischemic stroke.

Ischemic stroke, which results in loss of neurological function, initiates a complex cascade of pathological events in the brain, largely driven by excitotoxic Ca2+ influx in neurons. This leads to cortical spreading depolarization, which induces expression of genes involved in both neuronal death and survival; yet, the functions of these genes remain poorly understood. Here, we profiled gene expression changes that are common to ischemia (modeled by middle cerebral artery occlusion [MCAO]) and to experience-dependent activation (modeled by exposure to an enriched environment [EE]), which also induces Ca2+ transients that trigger transcriptional programs. We found that the activity-dependent transcription factor Npas4 was up-regulated under MCAO and EE conditions and that transient activation of cortical neurons in the healthy brain by the EE decreased cell death after stroke. Furthermore, both MCAO in vivo and oxygen-glucose deprivation in vitro revealed that Npas4 is necessary and sufficient for neuroprotection. We also found that this protection involves the inhibition of L-type voltage-gated Ca2+ channels (VGCCs). Next, our systematic search for Npas4-downstream genes identified Gem, which encodes a Ras-related small GTPase that mediates neuroprotective effects of Npas4. Gem suppresses the membrane localization of L-type VGCCs to inhibit excess Ca2+ influx, thereby protecting neurons from excitotoxic death after in vitro and in vivo ischemia. Collectively, our findings indicate that Gem expression via Npas4 is necessary and sufficient to promote neuroprotection in the injured brain. Importantly, Gem is also induced in human cerebral organoids cultured under an ischemic condition, revealing Gem as a new target for drug discovery.

Assessment of the accuracy of an intermittent-scanning continuous glucose monitoring device in patients with type 2 diabetes mellitus undergoing hemodialysis (AIDT2H) study.

FreeStyle Libre has been approved for use in patients undergoing hemodialysis (HD) in Japan, unlike Europe and the United States; however, evidence regarding its accuracy in such patients is sparse. Forty-one participants with type 2 diabetes undergoing HD were recruited. The overall mean absolute relative difference and mean absolute difference were 23.4% and 33.9 mg/dL, respectively. Sensor glucose levels and capillary glucose levels were significantly correlated (r = 0.858, P < .01), although the sensor glucose levels were significantly lower than the capillary glucose levels. The accuracy of FreeStyle Libre in patients undergoing HD became deteriorated with the days of usage. The percentage of sensor results in Zones A and B in the consensus error grid analysis and in the Clarke error grid analysis were 99.7% and 99.0%, respectively. Its insufficient accuracy necessitates adjunct usage of FreeStyle Libre with self-monitoring of blood glucose in patients undergoing HD.

Spatial optimization of invasive species control informed by management practices.

Optimization of spatial resource allocation is crucial for the successful control of invasive species under a limited budget but requires labor-intensive surveys to estimate population parameters. In this study, we devised a novel framework for the spatially explicit optimization of capture effort allocation using state-space population models from past capture records. We applied it to a control program for invasive snapping turtles to determine effort allocation strategies that minimize the population density over the whole area. We found that spatially heterogeneous density dependence and capture pressure limit the abundance of snapping turtles. Optimal effort allocation effectively improved the control effect, but the degree of improvement varied substantially depending on the total effort. The degree of improvement by the spatial optimization of allocation effort was only 3.21% when the total effort was maintained at the 2016 level. However, when the total effort was increased by two, four, and eight times, spatial optimization resulted in improvements of 4.65%, 8.33%, and 20.35%, respectively. To achieve the management goal for snapping turtles in our study area, increasing the current total effort by more than four times was necessary, in addition to optimizing the spatial effort. The snapping turtle population is expected to reach the target density one year after the optimal management strategy is implemented, and this rapid response can be explained by high population growth rate coupled with density-dependent feedback regulation. Our results demonstrated that combining a state-space model with optimization makes it possible to adaptively improve the management of invasive species and decision-making. The method used in this study, based on removal records from an invasive management program, can be easily applied to monitoring data for wildlife and pest control management using traps in a variety of ecosystems.

Retinal ganglion cell loss in kinesin-1 cargo Alcadein α deficient mice.

Maintenance of retinal ganglion cells (RGCs) activity is relied on axonal transport conveying materials required for their survival such as neurotrophic factors. Kinesin-1 undergoes anterograde transport in axons, and Alcadein α (Alcα; also called calsyntenin-1) is a major cargo adaptor protein that can drive kinesin-1 to transport vesicles containing Alcα. The long-term effects of Alcα-deficiency on retinal morphology and survival of RGCs during postnatal development were examined in Alcα knockout mice. At 1.5, 3, 6, and 15 months postnatal, the number of retrogradely labeled RGCs was determined in flat-mounted retinas of Alcα-deficient and wild-type mice. Retinal damage was assessed histologically by determining the retinal thickness. Intraocular pressure (IOP) was measured with a Tonolab tonometer. At 1.5 months postnatal, the number of retrogradely labeled RGCs was not different between wild-type and Alcα-deficient mice. However, at 3, 6, and 15 months postnatal, the number of RGCs was significantly lower in Alcα deficient mice than those of wild-type mice (143 ± 41.1 cells/mm2 vs. 208 ± 28.4 cells/mm2, respectively, at 3 months; P < 0.01). No differences were seen in retinal thickness or IOP between the two types of mice at any postnatal age. Alcα-deficient mice showed spontaneous loss of RGCs but no elevation in IOP. These mice mimic normal-tension glaucoma and will be useful for investigating the mechanism of neurodegeneration in this disorder and for developing treatments for RGC loss that does not involve changes in IOP.

MDGA1-deficiency attenuates prepulse inhibition with alterations of dopamine and serotonin metabolism: An ex vivo HPLC-ECD analysis.

MDGA1 (MAM domain-containing glycosylphosphatidylinositol anchor) has recently been linked to schizophrenia and bipolar disorder. Dysregulation of dopamine (DA) and serotonin (5-HT) systems has long been associated with schizophrenia and other neuropsychiatric disorders. Here, we measured prepulse inhibition (PPI) of the startle response and ex vivo tissue content of monoamines and their metabolites in the frontal cortex, striatum and hippocampus of Mdga1 homozygous (Mdga1-KO), Mdga1 heterozygous (Mdga1-HT) and wild-type (WT) male mice. We found that Mdga1-KO mice exhibited statistically significant impairment of PPI, and had higher levels of homovanillic acid in all three brain regions studied compared with Mdga1-HT and WT mice (P < 0.05), while levels of norepinephrine, DA and its metabolites 3,4-dihydroxyphenylacetic acid and 3-methoxytyramine remained unchanged. Mdga1-KO mice also had a lower 5-hydroxyindoleacetic acid level in the striatum (P < 0.05) compared with WT mice. 5-HT levels remained unchanged with the exception of a significant increase in the level in the cortex. These data are the first evidence suggesting that MDGA1 deficiency leads to a pronounced deficit in PPI and plays an important role in perturbation of DA and 5-HT metabolism in mouse brain; such changes may contribute to a range of neuropsychiatric disorders.

Expression of Oncofetal Antigen 5T4 in Murine Taste Papillae.

Background: Multicellular taste buds located within taste papillae on the tongue mediate taste sensation. In taste papillae, taste bud cells (TBCs), such as taste receptor cells and taste precursor cells, and the surrounding lingual epithelium including epithelial progenitors (also called taste stem/progenitor cells) are maintained by continuous cell turnover throughout life. However, it remains unknown how the cells constituting taste buds proliferate and differentiate to maintain taste bud tissue. Based on in situ hybridization (ISH) screening, we demonstrated that the oncofetal antigen 5T4 (also known as trophoblast glycoprotein: TPBG) gene is expressed in the adult mouse tongue. Results: In immunohistochemistry of coronal tongue sections, 5T4 protein was detected at a low level exclusively in the basal part of the lingual epithelium in developing and adult mice, and at a high level particularly in foliate papillae and circumvallate papillae (CVPs). Furthermore, immunohistochemistry of the basal part of CVPs indicated that the proliferation marker PCNA (proliferating cell nuclear antigen) co-localized with 5T4. 5T4 was strongly expressed in Krt5+ epithelial progenitors and Shh+ taste precursor cells, but weakly in mature taste receptor cells. The number of proliferating cells in the CVP was higher in 5T4-knockout mice than in wild-type (WT) mice, while neither cell differentiation nor the size of taste buds differed between these two groups of mice. Notably, X-ray irradiation enhanced cell proliferation more in 5T4-knockout mice than in WT mice. Conclusion: Our results suggest that 5T4, expressed in epithelial progenitors (taste stem/progenitor cells), and taste precursor cells, may influence the maintenance of taste papillae under both normal and injury conditions.

Dual benefit of supplementary oral 5-aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model.

BACKGROUND: Normal tissue damage caused by radiotherapy remains the largest dose-limiting factor in radiotherapy for cancer. Therefore, the aim of this study was to investigate the supplementary oral 5-aminolevulinic acid (ALA) to standard radiation therapy as a novel radioprotective approach that would not compromise the antitumor effect of radiation in normal rectal and bladder mucosa in a syngenic prostate cancer (PCa) model. METHODS: To evaluate the radiosensitizing effect of ALA in vitro, clonogenic survival assays were performed in DU145, PC3, and MyC-CaP cell lines. To evaluate the effect of ALA in vivo a single dose (25 Gy) of radiation with or without ALA was given to healthy mice. Next, a syngenic PCa model of MyC-CaP cells in FVB mice was created, and multiple doses (12 Gy total) of radiation were administered to the mouse pelvic area with or without ALA administration. Resected tumors, recta, and urinary bladders were immunostained with antibodies against Ki-67, γ-H2AX, CD204, and uroplakin-III. Total RNA levels in recta and urinary bladders were analyzed via RT2 Profiler polymerase chain reaction (PCR) arrays related to "Stress & Toxicity PathwayFinder," "Mitochondria," and "Inflammasomes." RESULTS: The addition of in vitro single or in vivo repeated administration of exogenous ALA acted as a radiosensitizer for PCa cells. Rectal toxicity was characterized by histological changes including loss of surface epithelium, fibrosis, severe DNA damage, and the aggregation of M2 macrophages. Urinary bladder toxicity was characterized by bladder wall thickening and urothelium denuding. The higher dose (300 mg/kg/day) of ALA exerted a better radioprotective profile than the lower dose (30 mg/kg/day) in normal recta and urinary bladders. Out of the 252 genes tested, 35 (13.4%) were detected as relevant genes which may be involved in the radioprotective role of ALA administration. These included interleukin-1a (IL-1a), IL-1b, IL-12, chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL3, and NLRP3. CONCLUSIONS: Our study provides novel and comprehensive insights into the dual benefits including radiosensitizing PCa tumor tissues and radioprotection of normal pelvic organs from radiation therapy. Knowledge of the underlying mechanism will facilitate the search for optimal treatment parameters for supplemental oral ALA during radiotherapy for PCa.

The Functional Role of Olfactory Bulb Granule Cell Subtypes Derived From Embryonic and Postnatal Neurogenesis.

It has been shown in a variety of mammalian species that sensory experience can regulate the development of various structures, including the retina, cortex, hippocampus, and olfactory bulb (OB). In the mammalian OB, the development of dendrites in excitatory projection neurons, such as mitral and tufted cells, is well known to be dependent on odor experience. Odor experience is also involved in the development of another OB population, a subset of inhibitory interneurons that are generated in the ventricular-subventricular zone throughout life and differentiate into granule cells (GCs) and periglomerular cells. However, the roles that each type of interneuron plays in the control of olfactory behaviors are incompletely understood. We recently found that among the various types of OB interneurons, a subtype of GCs expressing the oncofetal trophoblast glycoprotein 5T4 gene is required for odor detection and discrimination behaviors. Our results suggest that embryonic-born OB interneurons, including 5T4-positive GCs, play a crucial role in fundamental olfactory responses such as simple odor detection and discrimination behaviors. By contrast, postnatal- and adult-born OB interneurons are important in the learning of more complicated olfactory behaviors. Here, we highlight the subtypes of OB GCs, and discuss their roles in olfactory processing and behavior, with a particular focus on the relative contributions of embryonically and postnatally generated subsets of GCs in rodents.

Olfactory Avoidance Test (Mouse).

In mice, olfaction plays a pivotal role in the various behaviors, such as feeding, mating, nursing and avoidance. Behavioral tests that analyze abilities of odor detection and recognition using genetically modified mice reveal the contribution of target genes to the olfactory processing. Here, we describe the olfactory avoidance test to investigate the odor detection ability in mice.

Olfactory Habituation-dishabituation Test (Mouse).

Olfaction plays a fundamental role in the various behaviors such as feeding, mating, nursing, and avoidance in mice. Behavioral tests that characterize abilities of odor detection and recognition using genetically modified mice reveal the contribution of target genes to the olfactory processing. Here, we describe the olfactory habituation-dishabituation test for investigating the odor detection threshold in mice.