A GnRH neuronal population in the olfactory bulb translates socially relevant odors into reproductive behavior in male mice.

Hypothalamic gonadotropin-releasing hormone (GnRH) neurons regulate fertility and integrate hormonal status with environmental cues to ensure reproductive success. Here we show that GnRH neurons in the olfactory bulb (GnRHOB) of adult mice can mediate social recognition. Specifically, we show that GnRHOB neurons extend neurites into the vomeronasal organ and olfactory epithelium and project to the median eminence. GnRHOB neurons in males express vomeronasal and olfactory receptors, are activated by female odors and mediate gonadotropin release in response to female urine. Male preference for female odors required the presence and activation of GnRHOB neurons, was impaired after genetic inhibition or ablation of these cells and relied on GnRH signaling in the posterodorsal medial amygdala. GnRH receptor expression in amygdala kisspeptin neurons appear to be required for GnRHOB neurons' actions on male mounting behavior. Taken together, these results establish GnRHOB neurons as regulating fertility, sex recognition and mating in male mice.

Estrogen deficiency affects synchronized neural connectivity in the olfactory bulb-nucleus accumbens circuit: A local field potential study in ovariectomized mouse model.

Estrogen plays a crucial role in regulating various brain functions, including cognitive, emotional, and social behaviors. Menopausal women face a decline in estrogen levels, which has been linked to several physical and mental health issues. However, the impact of estrogen on the olfactory bulb-nucleus accumbens (OB-NAc) circuit, which is essential for regulating emotions and cognitive behaviors, remains poorly understood. To test the hypothesis that estrogen deficiency affects signal processing, we recorded local field potentials (LFPs) using intracranial electrodes implanted in four-week-old ovariectomized (OVX) mice during an open-field test (OFT). The results showed a decrease in locomotor activity and increase in anxiety-like behaviors in OVX mice. Furthermore, we found a decrease in high-gamma power in the OB. We analyzed coherence and inter-region phase-amplitude coupling (ir-PAC) to explore the connectivity between the OB and NAc. We observed a decrease in low-gamma and high-gamma coherence in OVX mice. Additionally, we found that the direction of connectivity from the NAc to the OB was disrupted in OVX mice. In summary, our study provides evidence that estrogen deficiency is linked to synchronized neural connectivity changes in the OB-NAc circuit. These findings have implications for our understanding of the roles played by the OB-NAc neural circuit and estrogen in the regulation of general exploratory behavior and anxiety-like behavior.

A method for detecting spatiotemporal patterns of cancer biomarkers-evoked activity using radial basis function network extracted time-domain features from calcium imaging data.

BACKGROUND: Two-photon calcium imaging is widely used to study the odor-evoked glomerular activity in the dorsal olfactory bulb of macrosmatic animals. The nonstationary character of activated patterns sets a limit on the use of a traditional image processing approaches. NEW METHOD: The developed method makes it possible to automatically map cancer biomarkers-activated glomeruli in the rat dorsal olfactory bulb. We interpolated fluorescence intensity of calcium dynamics based on the Gaussian RBF network and synthesized the physiological fluorescence model of the receptive glomerular field. RESULTS: The experiments on 5 rats confirmed the correctness of the developed approach. Patterns evoked by the 6-methyl-5-hepten-2-one (stomach cancer biomarker) and benzene (lung cancer biomarker) were correctly identified. COMPARISON WITH EXISTING METHODS: The proposed method was compared with the nonnegative matrix factorization method and with the method based on computer vision algorithms. The developed approach showed better accuracy in experiments and provided the mathematical models of the odor-evoked patterns synthesis. These models can be used to generate synthetic images of odor-evoked glomerular activity and thus to overcome the problem of small experimental data collected in calcium imaging. CONCLUSIONS: The proposed method should be considered part of the toolkit for fully automatic analysis of calcium imaging-based studies. Currently available methodology is not able to use breath biomarkers to reliably discriminate between cancer patients and healthy controls. Nevertheless, the effective identification of the spatial patterns of cancer biomarkers-evoked glomerular activity can serve as the foundation for highly sensitive biohybrid systems for cancer screening.

Surgical Approaches for Possible Positions of an Olfactory Implant to Stimulate the Olfactory Bulb.

INTRODUCTION: Current scientific developments seem to allow for an "olfactory implant" in analogy to cochlear implants. However, the position and surgical approaches for electrical stimulation of the olfactory system are unclear. METHODS: In a human anatomic cadaver study, we investigated different endoscopic approaches to electrically stimulate the olfactory bulb (OB) based on the following considerations: (1) the stimulating electrode should be close to the OB. (2) The surgical procedure should be as non-invasive and safe as possible and (3) as easy as possible for an experienced ENT surgeon. RESULTS: In summary, the endoscopic intracranial positioning of the electrode via a widened ostium of the fila olfactoria or a frontal sinus surgery like a Draf IIb procedure is a good option in terms of patients' risk, degree of difficulty for ENT surgeons, and position to the OB. Endoscopic intranasal positioning appeared to be the best option in terms of patient risk and the degree of difficulty for ENT surgeons. Although a bigger approach to the OB using a drill and the combined intranasal endoscopic and external approach enabled a close placement of the electrode to the OB, they do not seem relevant in practice due to their higher invasiveness. CONCLUSION: The study suggested that an intranasal positioning of a stimulating electrode is possible, with placements beneath the cribriform plate, extra- or intracranially, applying elegant surgical techniques with low or medium risk to the patient and a close placement to OB.

VIP interneurons regulate olfactory bulb output and contribute to odor detection and discrimination.

In the olfactory bulb (OB), olfactory information represented by mitral/tufted cells (M/Ts) is extensively modulated by local inhibitory interneurons before being transmitted to the olfactory cortex. While the crucial roles of cortical vasoactive-intestinal-peptide-expressing (VIP) interneurons have been extensively studied, their precise function in the OB remains elusive. Here, we identify the synaptic connectivity of VIP interneurons onto mitral cells (MCs) and demonstrate their important role in olfactory behaviors. Optogenetic activation of VIP interneurons reduced both spontaneous and odor-evoked activity of M/Ts in awake mice. Whole-cell recordings revealed that VIP interneurons decrease MC firing through direct inhibitory synaptic connections with MCs. Furthermore, inactivation of VIP interneurons leads to increased MC firing and impaired olfactory detection and odor discrimination. Therefore, our results demonstrate that VIP interneurons control OB output and play critical roles in odor processing and olfactory behaviors.

Ablation of microRNAs in VIP+ interneurons impairs olfactory discrimination and decreases neural activity in the olfactory bulb.

AIM: MicroRNAs (miRNAs) are abundantly expressed in vasoactive intestinal peptide expressing (VIP+ ) interneurons and are indispensable for their functional maintenance and survival. Here, we blocked miRNA biogenesis in postmitotic VIP+ interneurons in mice by selectively ablating Dicer, an enzyme essential for miRNA maturation, to study whether ablation of VIP+ miRNA affects olfactory function and neural activity in olfactory centres such as the olfactory bulb, which contains a large number of VIP+ interneurons. METHODS: A go/no-go odour discrimination task and a food-seeking test were used to assess olfactory discrimination and olfactory detection. In vivo electrophysiological techniques were used to record single units and local field potentials. RESULTS: Olfactory detection and olfactory discrimination behaviours were impaired in VIP+ -specific Dicer-knockout mice. In vivo electrophysiological recordings in awake, head-fixed mice showed that both spontaneous and odour-evoked firing rates were decreased in mitral/tufted cells in knockout mice. The power of ongoing and odour-evoked beta local field potentials response of the olfactory bulb and anterior piriform cortex were dramatically decreased. Furthermore, the coherence of theta oscillations between the olfactory bulb and anterior piriform cortex was decreased. Importantly, Dicer knockout restricted to olfactory bulb VIP+ interneurons recapitulated the behavioural and electrophysiological results of the global knockout. CONCLUSIONS: VIP+ miRNAs are an important factor in sensory processing, affecting olfactory function and olfactory neural activity.

Association between Airport-Related Ultrafine Particles and Risk of Malignant Brain Cancer: A Multiethnic Cohort Study.

Ultrafine particles (UFP; diameter less than or equal to 100 nm) may reach the brain via systemic circulation or the olfactory tract and have been implicated in the risk of brain tumors. The effects of airport-related UFP on the risk of brain tumors are not known. Here we determined the association between airport-related UFP and risk of incident malignant brain cancer (n = 155) and meningioma (n = 420) diagnosed during 16.4 years of follow-up among 75,936 men and women residing in Los Angeles County from the Multiethnic Cohort study. UFP exposure from aircrafts was estimated for participants who lived within a 53 km × 43 km grid area around the Los Angeles International Airport (LAX) from date of cohort entry (1993-1996) through December 31, 2013. Cox proportional hazards models were used to estimate the effects of time-varying, airport-related UFP exposure on risk of malignant brain cancer and meningioma, adjusting for sex, race/ethnicity, education, and neighborhood socioeconomic status. Malignant brain cancer risk in all subjects combined increased 12% [95% confidence interval (CI), 0.98-1.27] per interquartile range (IQR) of airport-related UFP exposure (∼6,700 particles/cm3) for subjects with any address in the grid area surrounding the LAX airport. In race/ethnicity-stratified analyses, African Americans, the subgroup who had the highest exposure, showed a HR of 1.32 (95% CI, 1.07-1.64) for malignant brain cancer per IQR in UFP exposure. UFP exposure was not related to risk of meningioma overall or by race/ethnicity. These results support the hypothesis that airport-related UFP exposure may be a risk factor for malignant brain cancers. SIGNIFICANCE: Malignant brain cancer risk increases with airport-related UFP exposure, particularly among African Americans, suggesting UFP exposure may be a modifiable risk factor for malignant brain cancer.

The Grueneberg ganglion: signal transduction and coding in an olfactory and thermosensory organ involved in the detection of alarm pheromones and predator-secreted kairomones.

In numerous mammalian species, the nose harbors several compartments populated by chemosensory cells. Among them, the Grueneberg ganglion (GG) located in the anterior nasal region comprises sensory neurons activated by given substances. In rodents, in which the GG has been best studied, these chemical cues mainly include heterocyclic compounds released by predators or by conspecifics. Since some of these substances evoke fear- or stress-associated responses, the GG is considered as a detector for alerting semiochemicals. In fact, certain behavioral and physiological reactions to alarm pheromones and predator-secreted kairomones are attenuated in the absence of a functional GG. Intriguingly, GG neurons are also stimulated by cool temperatures. Moreover, ambient temperatures modulate olfactory responsiveness in the GG, indicating that cross-talks exist between the transduction pathways mediating chemo- and thermosensory signaling in this organ. In this context, exploring the relevant molecular cascades has demonstrated that some chemosensory transduction elements are also crucial for thermosensory signaling in the GG. Finally, for further processing of sensory information, axons of GG neurons project to the olfactory bulb of the brain where they innervate distinct glomerular structures belonging to the enigmatic necklace glomeruli. In this review, the stimuli activating GG neurons as well as the underlying transduction pathways are summarized. Because these stimuli do not exclusively activate GG neurons but also other sensory cells, the biological relevance of the GG is discussed, with a special focus on the role of the GG in detecting alarm signals.

Developmental Profile of Brain Neprilysin Expression Correlates with Olfactory Behaviour of Rats.

A neuropeptidase, neprilysin (NEP), is a major amyloid (Aß)-degrading enzyme involved in the pathogenesis of Alzheimer's disease (AD). The olfactory system is affected early in AD with characteristic Aß accumulation, but data on the dynamics of NEP expression in the olfactory system are absent. Our study demonstrates that NEP mRNA expression in rat olfactory bulbs (OB), entorhinal cortex (ECx), hippocampus (Hip), parietal cortex (PCx) and striatum (Str) increases during the first postnatal month being the highest in the OB and Str. By 3 months, NEP mRNA levels sharply decrease in the ECx, Hip and PCx and by 9 months in the OB, but not in the Str, which correlates with declining olfaction in aged rats tested in the food search paradigm. One-month-old rats subjected to prenatal hypoxia on E14 had lower NEP mRNA levels in the ECx, Hip and PCx (but not in the OB and Str) compared with the control offspring and demonstrated impaired olfaction in the odour preference and food search paradigms. Administration to these rats of a histone deacetylase inhibitor, sodium valproate, restored NEP expression in the ECx, Hip and PCx and improved olfaction. Our data support NEP involvement in olfactory function.

The evolutionary origins of the vertebrate olfactory system.

Vertebrates develop an olfactory system that detects odorants and pheromones through their interaction with specialized cell surface receptors on olfactory sensory neurons. During development, the olfactory system forms from the olfactory placodes, specialized areas of the anterior ectoderm that share cellular and molecular properties with placodes involved in the development of other cranial senses. The early-diverging chordate lineages amphioxus, tunicates, lampreys and hagfishes give insight into how this system evolved. Here, we review olfactory system development and cell types in these lineages alongside chemosensory receptor gene evolution, integrating these data into a description of how the vertebrate olfactory system evolved. Some olfactory system cell types predate the vertebrates, as do some of the mechanisms specifying placodes, and it is likely these two were already connected in the common ancestor of vertebrates and tunicates. In stem vertebrates, this evolved into an organ system integrating additional tissues and morphogenetic processes defining distinct olfactory and adenohypophyseal components, followed by splitting of the ancestral placode to produce the characteristic paired olfactory organs of most modern vertebrates.

Aging Alters Olfactory Bulb Network Oscillations and Connectivity: Relevance for Aging-Related Neurodegeneration Studies.

The aging process eventually cause a breakdown in critical synaptic plasticity and connectivity leading to deficits in memory function. The olfactory bulb (OB) and the hippocampus, both regions of the brain considered critical for the processing of odors and spatial memory, are commonly affected by aging. Using an aged wild-type C57B/6 mouse model, we sought to define the effects of aging on hippocampal plasticity and the integrity of cortical circuits. Specifically, we measured the long-term potentiation of high-frequency stimulation (HFS-LTP) at the Shaffer-Collateral CA1 pyramidal synapses. Next, local field potential (LFP) spectra, phase-amplitude theta-gamma coupling (PAC), and connectivity through coherence were assessed in the olfactory bulb, frontal and entorhinal cortices, CA1, and amygdala circuits. The OB of aged mice showed a significant increase in the number of histone H2AX-positive neurons, a marker of DNA damage. While the input-output relationship measure of basal synaptic activity was found not to differ between young and aged mice, a pronounced decline in the slope of field excitatory postsynaptic potential (fEPSP) and the population spike amplitude (PSA) were found in aged mice. Furthermore, aging was accompanied by deficits in gamma network oscillations, a shift to slow oscillations, reduced coherence and theta-gamma PAC in the OB circuit. Thus, while the basal synaptic activity was unaltered in older mice, impairment in hippocampal synaptic transmission was observed only in response to HFS. However, age-dependent alterations in neural network appeared spontaneously in the OB circuit, suggesting the neurophysiological basis of synaptic deficits underlying olfactory processing. Taken together, the results highlight the sensitivity and therefore potential use of LFP quantitative network oscillations and connectivity at the OB level as objective electrophysiological markers that will help reveal specific dysfunctional circuits in aging-related neurodegeneration studies.

Double recording system of Period1 gene expression rhythm in the olfactory bulb and liver in freely moving mouse.

Clock genes express circadian rhythms in most organs. These rhythms are organized throughout the whole body, regulated by the suprachiasmatic nucleus (SCN) in the brain. Disturbance of these clock gene expression rhythms is a risk factor for diseases such as obesity and cancer. To understand the mechanism of regulating clock gene expression rhythms in vivo, multiple real time recording systems are required. In the present study, we developed a double recording system of Period1 expression rhythm in peripheral tissue (liver) and the brain. In peripheral tissue, quantification of gene expression in a steadily moving target was achieved by using a photomultiplier tube (PMT) attached to a tissue contact optical sensor (TCS). Using this technique, we were able to analyze circadian rhythms of clock gene expression over a prolonged period in the liver and olfactory bub (OB) of the brain. The present double recording system has no effect on behavioral activity or rhythm. Our novel system thus successfully quantifies clock gene expression in deep areas of the body in freely moving mice for a period sufficient to analyze circadian dynamics. In addition, our double recording system can be widely applied to many areas of biomedical research, as well as applications beyond medicine.

Liver hydrolysate improves depressive-like behavior in olfactory bulbectomized mice: Involvement of hippocampal neurogenesis through the AMPK/BDNF/CREB pathway.

Recently, we has reported that AMPK activator has antidepressant effect. Previous our study suggested that liver hydrolysate (LH) activated adenosine monophosphate-activated protein kinase (AMPK) in periphery. However, the effect of LH on depression is unclear. Therefore, we examines whether LH has antidepressant effect on olfactory bulbectomized (OBX) mice. OBX mice showed depressive-like behavior in tail-suspension test and reduction of hippocampal neurogenesis, while these changes were reversed by LH. LH enhanced hippocampal phosphate-AMPK, brain-derived neurotrophic factor (BDNF) and phosphate-cyclic adenosine monophosphate response element-binding protein (CREB) in OBX mice. These data indicate that LH may produce antidepressant effects via hippocampal AMPK/BDNF/CREB signaling.

Simultaneous activities in both mirror-image glomerular maps in the olfactory bulb may have an important role in stress-related neuronal responses in mice.

In the mouse olfactory bulb (OB), odor input from the olfactory epithelium innervates topographically to form odorant maps, which are mirror-image arrangements of glomerular clusters with domain organization. However, the functional role of the mirror-image representation in the OB remains unknown. Predator odors induce stress responses, and the dorsal domain of the dorsolateral wall of the olfactory bulb (dlOB) is known to be involved in this process. However, it remains unclear whether the activities in the medial wall of the OB (mOB), the other mirror half, are also involved in stress responses. Therefore, in this study, we investigated whether the mOB and dlOB are required for the induction of stress responses using lesioning or electrical stimulation. Although there were no significant differences in the number of activated neurons in the bed nucleus of the stria terminalis, posterior piriform cortex or amygdalo-piriform transition area, fewer activated neurons were observed in the anterior piriform cortex (APC) following lesion of both the mOB and dlOB combined. No changes were observed in the density of activated cells in any examined brain region following stimulation of either the mOB or dlOB alone. However, activated neurons in the APC were significantly more numerous following simultaneous stimulation of the mOB and dlOB. Collectively, our results suggest that simultaneous activation in both the mOB and dlOB is needed to induce APC neural activities that produce stress-like behavior. These findings provide insight into olfactory information processing, and may also help in the development of therapies for odor-induced stress behaviors.

Neurogenic Niche Conversion Strategy Induces Migration and Functional Neuronal Differentiation of Neural Precursor Cells Following Brain Injury.

Glial scars formed after brain injuries provide permissive cues for endogenous neural precursor/stem cells (eNP/SCs) to undergo astrogenesis rather than neurogenesis. Following brain injury, eNP/SCs from the subventricular zone leave their niche, migrate to the injured cortex, and differentiate into reactive astrocytes that contribute to glial scar formation. In vivo neuronal reprogramming, directly converting non-neuronal cells such as reactive astrocytes or NG2 glia into neurons, has greatly improved brain injury repair strategies. However, reprogramming carries a high risk of future clinical applications such as tumorigenicity, involving virus. In this study, we constructed a neural matrix to alter the adverse niche at the injured cortex, enabling eNP/SCs to differentiate into functional neurons. We found that the neural matrix functioned as a "glial trap" that largely concentrated and limited reactive astrocytes to the core of the lesion area, thus altering the adverse niche. The eNP/SCs migrated toward the injured cortex and differentiated into functional neurons. In addition, regenerated neurites extended across the boundary of the injured cortex. Mice treated with the neural matrix demonstrated significant behavioral recovery. For the first time, we induced eNP/SC-derived functional neurons in the cortex after brain injury without the use of viruses, microRNAs, or small molecules. Our novel strategy of applying this "glial trap" to obtain functional neurons in the injured cortex may provide a safer and more natural therapeutic alternative to reprogramming in future clinical applications.

Involvement of Adult-born and Preexisting Olfactory Bulb and Dentate Gyrus Neurons in Single-trial Olfactory Memory Acquisition and Retrieval.

The production of new neurons and their incorporation into preexisting neuronal circuits occur throughout adulthood in the olfactory bulb and the hippocampal dentate gyrus of the mammalian brain. To determine whether the adult-born neurons are engaged in the acquisition and retrieval of olfactory associative memory, we developed and validated a single-trial olfactory fear conditioning protocol in mice which allows to detect activation of newborn neurons during a specific episode of memory acquisition. Using c-Fos mapping of neuronal activity, we then examined the activation of new and preexisting neurons during training and testing sessions. We found that a single trial of olfactory fear conditioning did not lead to a significant increase in the number of c-Fos-positive granule cells (GCs) of the olfactory bulb and the dentate gyrus. However, the activity of these two cell populations was dramatically increased during memory retrieval. Activation of neurons in the dentate gyrus during memory retrieval was observed mainly in the suprapyramidal blade. In the olfactory bulb, 1.6-2.7% of newborn GCs marked with thymidine analogues (2, 4, and 6 weeks old) expressed c-Fos during memory retrieval, while in the dentate gyrus no newborn neurons were found among the c-Fos-positive cells. These data are consistent with the hypothesis that adult-born GCs of the olfactory bulb are less involved in odor-cued associative fear memory than in odor-cued operant behavior memory.

PTENα regulates endocytosis and modulates olfactory function.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) α is the first identified isoform of the well-known tumor suppressor PTEN. PTENα has an evolutionarily conserved 173-aa N terminus compared with canonical PTEN. Recently, PTENα has been shown to play roles in multiple biologic processes including learning and memory, cardiac homeostasis, and antiviral immunity. Here, we report that PTENα maintains mitral cells in olfactory bulb (OB), regulates endocytosis in OB neurons, and controls olfactory behaviors in mice. We show that PTENα directly dephosphorylates the endocytic protein amphiphysin and promotes its binding to adaptor-related protein complex 2 subunit ß1 (Ap2b1). In addition, we identified mutations in the N terminus of PTENα in patients with Parkinson disease and Lewy-body dementia, which are neurodegenerative disorders with early olfactory loss. Overexpression of PTENα mutant H169N in mice OB reduces odor sensitivity. Our data demonstrate a role of PTENα in olfactory function and provide insight into the mechanism of olfactory dysfunction in neurologic disorders.-Yuan, Y., Zhao, X., Wang, P., Mei, F., Zhou, J., Jin, Y., McNutt, M. A., Yin, Y. PTENα regulates endocytosis and modulates olfactory function.

S 47445 counteracts the behavioral manifestations and hippocampal neuroplasticity changes in bulbectomized mice.

S 47445 is a positive allosteric modulator of glutamate AMPA-type receptors that possesses procognitive, neurotrophic and enhancing synaptic plasticity properties. Its chronic administration promotes antidepressant- and anxiolytic-like effects in different rodent models of depression. We have evaluated the behavioral effects of S 47445 in the bilateral olfactory bulbectomy mice model (OB) and the adaptive changes in those proteins associated to brain neuroplasticity (BDNF and mTOR pathway). Following OB surgery, adult C57BL/6J male mice were chronically administered S 47445 (1, 3 and 10 mg/kg/day; i.p.) and fluoxetine (18 mg/kg/day; i.p.), and then behaviorally tested in the open field test. Afterwards, the expression levels of BDNF, mTOR, phospho-mTOR, 4EBP1 and phospho-4EBP1 were evaluated in hippocampus and prefrontal cortex. Both drugs reduced the OB-induced locomotor activity, a predictive outcome of antidepressant efficacy, with a similar temporal pattern of action. S 47445, but not fluoxetine, showed an anxiolytic effect as reflected by an increased central activity. Chronic administration of S 47445 reversed OB-induced changes in BDNF and phopho-mTOR expression in hippocampus but not in prefrontal cortex. The chronic administration of S 47445 induced antidepressant- and anxiolytic-like effects at low-medium doses (1 and 3 mg/kg/day, i.p.) associated with the reversal of OB-induced changes in hippocampal BDNF and mTOR signaling pathways.

An increase in neural stem cells and olfactory bulb adult neurogenesis improves discrimination of highly similar odorants.

Adult neurogenesis is involved in cognitive performance but studies that manipulated this process to improve brain function are scarce. Here, we characterized a genetic mouse model in which neural stem cells (NSC) of the subventricular zone (SVZ) were temporarily expanded by conditional expression of the cell cycle regulators Cdk4/cyclinD1, thus increasing neurogenesis. We found that supernumerary neurons matured and integrated in the olfactory bulb similarly to physiologically generated newborn neurons displaying a correct expression of molecular markers, morphology and electrophysiological activity. Olfactory performance upon increased neurogenesis was unchanged when mice were tested on relatively easy tasks using distinct odor stimuli. In contrast, intriguingly, increasing neurogenesis improved the discrimination ability of mice when challenged with a difficult task using mixtures of highly similar odorants. Together, our study provides a mammalian model to control the expansion of somatic stem cells that can in principle be applied to any tissue for basic research and models of therapy. By applying this to NSC of the SVZ, we highlighted the importance of adult neurogenesis to specifically improve performance in a challenging olfactory task.

Neurogenesis in the adult hippocampus: history, regulation, and prospective roles.

BACKGROUND: The hippocampus is one of the sites in the mammalian brain that is capable of continuously generating controversy. Adult neurogenesis is a remarkable process, and yet an intensely debatable topic in contemporary neuroscience due to its distinctiveness and conceivable impact on neural activity. The belief that neurogenesis continues through adulthood has provoked remarkable efforts to describe how newborn neurons differentiate and incorporate into the adult brain. It has also encouraged studies that investigate the consequences of inadequate neurogenesis in neuropsychiatric and neurodegenerative diseases and explore the potential role of neural progenitor cells in brain repair. The adult nervous system is not static; it is subjected to morphological and physiological alterations at various levels. This plastic mechanism guarantees that the behavioral regulation of the adult nervous system is adaptable in response to varying environmental stimuli. Three regions of the adult brain, the olfactory bulb, the hypothalamus, and the hippocampal dentate gyrus, contain new-born neurons that exhibit an essential role in the natural functional circuitry of the adult brain. Purpose/Aim: This article explores current advancements in adult hippocampal neurogenesis by presenting its history and evolution and studying its association with neural plasticity. The article also discusses the prospective roles of adult hippocampal neurogenesis and describes the intracellular, extracellular, pathological, and environmental factors involved in its regulation. Abbreviations AHN Adult hippocampal neurogenesis AKT Protein kinase B BMP Bone Morphogenic Protein BrdU Bromodeoxyuridine CNS Central nervous system DG Dentate gyrus DISC1 Disrupted-in-schizophrenia 1 FGF-2 Fibroblast Growth Factor 2 GABA Gamma-aminobutyric acid Mbd1 Methyl-CpG-binding domain protein 1 Mecp2 Methyl-CpG-binding protein 2 mTOR Mammalian target of rapamycin NSCs Neural stem cells OB Olfactory bulb; P21: cyclin-dependent kinase inhibitor 1 RBPj Recombination Signal Binding protein for Immunoglobulin Kappa J Region RMS Rostral migratory Stream SGZ Subgranular zone Shh Sonic hedgehog SOX2 SRY (sex determining region Y)-box 2 SVZ Subventricular zone Wnt3 Wingless-type mouse mammary tumor virus.