In class 2 and 3 excitability, net-slow current is outward (hyperpolarizing) at perithreshold voltages and thus competes with fast current during spike initiation. Class 2 excitability exists if fast inward current overpowers slow outward current when constant stimulation exceeds threshold. Class 3 excitability exists if fast inward current overpowers slow outward current only during a stimulus transient, which precludes repetitive spiking during sustained stimulation. Thus, on the basis of whether fast and slow currents cooperate or compete at perithreshold voltages, three classes of excitability selleck chemicals llc arise from a continuum in the strength and direction

of net-slow current. The strength of net-fast current (which depends on leak current) affects its competition with net-slow current, thus influencing the boundary between class 2 and 3 excitability (Lundstrom et al., 2008; Prescott et al., 2008a). In dynamical terms, it is the cooperative versus competitive nature of the interaction controlling spike initiation that distinguishes

integration and coincidence detection. To be clear, net current depends on both activation and inactivation of contributing ion channels, meaning inactivation of an outward current has effects comparable to activation of an inward current if the two processes occur with similar kinetics and voltage dependency. Accordingly, and especially given that pyramidal neurons express a multitude of different Endonuclease ion channels, there are several distinct channel combinations that can implement equivalent spike initiation dynamics. That said, see more the interaction between membrane currents also depends on the stimulus waveform because subthreshold membrane currents are differentially activated or inactivated by stimuli with different kinetics. This speaks to the joint dependence

of spiking on neuronal properties and stimulus properties (see below for discussion on filtering). With respect to synaptic input, subthreshold inward current helps sustain the depolarization caused by excitatory inputs, thereby encouraging temporal summation (integration) in class 1 neurons; contrariwise, subthreshold outward current truncates the depolarization caused by excitatory inputs, thereby discouraging summation and allowing only coincident inputs that drive fast suprathreshold depolarization (i.e., faster than outward current can activate) to elicit spiking in class 2 and 3 neurons (Figure 4C). In effect, the width of the integration time window is regulated by the strength and direction of subthreshold currents (Fricker and Miles, 2000; Gastrein et al., 2011; Prescott and De Koninck, 2005). Note that the delayed negative feedback implemented by voltage-dependent outward current in class 2 and 3 neurons has an effect very similar to that mediated by feedforward synaptic inhibition, which is well recognized as a mechanism that limits the integration time window (e.g.

While the double mutation of R3 and D112 to serine (D112S-R3S) produced the largest disruption that we observed of ion selectivity, the charge swap (D112R-R3D) retained proton selectivity. Together, KU55933 these observations suggest that D112 and R3 interact electrostatically to contribute to the selectivity filter of the channel, and that mutation of R3 alone or in combination with D112S

induces a voltage sensor that leaks cations other than protons (Figure 8B). The number of mutations required to create a pore in a VSD provides information on the length and shape of the pore’s most constricted site. The “omega pore” through the VSD of the Shaker K+ channel requires a single mutation of the first arginine R1 to a small side chain (Tombola et al., 2005), leading to its opening when S4 is in the “down state” at hyperpolarized potentials. However, it appears that Shaker actually requires a double gap (substitution of two arginines) and that the outermost position (three residues before Shaker’s R1) is naturally “missing” (i.e., is an alanine), while an omega pore can also be made in Shaker at other voltages by mutations at neighboring CP-690550 pairs of arginines (Gamal El-Din et al., 2010). A double gap is also needed to create an omega pore through the

VSD in domain II of Nav1.2a, (Sokolov et al., 2005). However, in domain II of Nav1.4 channels, mutation of a single arginine (R2 or R3) is sufficient to make an omega current (Struyk et al., 2008, Sokolov et al., 2008 and Sokolov et al., 2010). We find that a single gap is sufficient for hHv1 to conduct Gu+, indicating that the pore of hHv1 is relatively short. As we observe here with hHv1, the Shaker omega pore is more permeable to Gu+ than to metal cations (Tombola et al., 2005). Moreover, Gu+ and protons have been found to be highly permeable through the VSD of domain II of Nav1.4 Na+ channel when 3-mercaptopyruvate sulfurtransferase a single arginine gap is made by substitution with glycine or histidine (Sokolov et al., 2010). Thus, the hHv1 VSD pore pathway shares with its counterparts from K+ and Na+ channels

a preference for the free ion that resembles the arginine side chain. A remarkable feature that appears to distinguish the omega pore of hHv1 from that of other channels is that arginine is uniquely able to select against Gu+, whereas other bulky or charged residues do not. Recent molecular dynamics simulations based on homology models built upon voltage-gated K+ channel crystal structures showed that water can occupy the core of the VSD of hHv1, but not of VSDs of tetrameric channels, suggesting that hHv1 may have evolved a specialized watery proton transfer pathway (Ramsey et al., 2010). Our findings are compatible with such a transfer pathway and with details of the homology model on which the simulations were based on, namely the close proximity of D112 to R3 in the activated state.

The

data suggest PMA and DAG enhance GTP exchange activity by recruiting RGEF-1b to internal membranes that contain transiently or persistently colocalized LET-60. C1 domains are composed of ∼50 amino acids and contain two His and six Cys residues that are conserved (Figure 7B). Collectively, the Cys and His side chains ligate two zinc ions, thereby creating a rigid structure that supports a binding pocket. Three β strands and two hydrophobic loops (A and B) (Figure 7B) generate surfaces that bind DAG/PMA and facilitate partial immersion of C1 domains into a lipid bilayer. A conserved Pro in loop A is critical for high-affinity PMA binding (Hurley and Misra, 2000). Consequently, Pro503 in RGEF-1b was mutated to Gly. The mutation extinguished basal GTP exchange (Figure 7C, lanes 1 and 3) buy Selumetinib and sharply suppressed GTP loading activity at a concentration of Selleckchem GS-7340 PMA (50 nM) that maximally activated WT RGEF-1b (Figure 7C, lanes 2 and 4; Figure 7D lane 1, upper and lower panels). However, incubation of cells with high concentrations of PMA (200–400 nM) elicited similar, maximal catalytic activities for RGEF-1bP503G and RGEF-1b (Figure 7D). The results indicate that the mutant exchanger folds normally, but Pro503 is essential for high-affinity PMA binding by the C1 domain. RGEF-1bP503G failed to activate LET-60 when bombesin triggered DAG synthesis (Figure 7C, lane 8). Bombesin peptide concentration (200 nM) was

20-fold higher than necessary to saturate bombesin receptors and optimally activate PLCβ (Feng et al., 2007). Thus, Pro503 is indispensable for coupling increased DAG content to RGEF-1b activation. Maximal, bombesin-induced production of DAG did not compensate for the diminished C1 domain function of RGEF-1bP503G. RGEF-1bP503G was

not stably recruited to membranes by 50 nM PMA or 200 nM bombesin (Figure 7Af and 7Ah). Evidently, transient association of RGEF-1bP503G with membrane-bound, nonmetabolized PMA was sufficient to modestly activate LET-60 (Figure 7C, lane 4). Reduced binding affinity of RGEF-1bP503G else for transiently synthesized, rapidly metabolized DAG prevented exchanger activation by endogenous second messenger (Figure 7C, lane 8). Thus, high-affinity DAG binding activity of the C1 domain is essential for intracellular targeting and maximal catalytic activity of RGEF-1b. In vivo consequences of RasGRP C1 domain dysfunction are unknown. Therefore, animals expressing rgef-1::RGEF-1b or rgef-1::RGEF-1bP503G transgenes (rgef-1−/− background) were incubated with odorants detected by AWC or AWA neurons. RGEF-1b restored chemotaxis to both odorants ( Figure 7E). In contrast, panneuronal expression of RGEF-1bP503G did not alter low CI values observed in RGEF-1b-deficient C. elegans ( Figure 7E). Thus, C1 domain-mediated targeting to membranes is a key determinant of a RasGRP function (chemotaxis) in vivo. MPK-1 phosphorylation was assayed to determine if the RGEF-1bP503G mutation affected signaling in AWC neurons.

Syt1 not only functions as a Ca2+ sensor for evoked synchronous release but also as a clamp for spontaneous minirelease (Littleton et al., 1993 and Maximov

and Südhof, 2005). As a result, the Syt1 KO significantly increases (>10-fold) spontaneous minirelease. In clamping minirelease, Syt1 does not actually clamp fusion but appears to inhibit a secondary Ca2+ sensor that mediates minirelease with a higher Ca2+ sensitivity (Xu et al., 2009 and Kochubey and Schneggenburger, 2011). The question thus arises whether Syt7 may represent the secondary Ca2+ sensor that is unclamped in Syt1 KO and KD neurons, or whether Syt7 may conversely also function as a clamp Bortezomib manufacturer for minirelease. We found that neither Syt7 overexpression nor the Syt7 KD had an effect on the frequency of mIPSCs in WT neurons (Figure 4A). Moreover, the Syt7 KD did not decrease the increased mIPSC frequency of Syt1 KO neurons (Figure 4B). Thus, although Syt7 is essential for asynchronous Ca2+-dependent release induced by high-frequency stimulus trains in Syt1 KO neurons, it is not required for the increased Ca2+-dependent spontaneous minirelease in these same neurons.

Strikingly, however, Syt7 overexpression reversed the increased minifrequency in Syt1 KO neurons without or with concurrent Syt7 KD (Figure 4B; see Figure S5 for protein quantifications showing that rescue of Syt7 KD neurons with WT Syt7 mediates Syt7 IDH inhibitor clinical trial overexpression). Note that in these experiments, the increase in mIPSC frequency in Syt1 KO neurons is probably underestimated because the mIPSC frequency is so high that even custom algorithms do not capture all events (see Experimental Procedures). Our data show that Syt7 is not a Ca2+ sensor for the increased

minievents in Syt1 KO neurons and does not clamp minis under physiological conditions but that at increased levels, Syt7 can substitute for Syt1 in clamping minirelease. A clamping function by Syt7 may not be apparent under physiological conditions because Syt7 may most not be expressed at sufficiently high levels, especially within presynaptic terminals. It is interesting that the ability of overexpressed Syt7 to clamp the increased minirelease in Syt1 KO neurons differs remarkably from the inability of overexpressed Syt7 to restore fast synchronous release in Syt1 KO neurons (Figures 3 and 4B; see also Xue et al., 2010). None of the Syt1 and/or Syt7 manipulations altered the mIPSC amplitude except for an apparent decrease in mIPSC amplitude upon Syt7 overexpression, which suppressed the increase in mIPSC frequency in Syt1-deficient neurons (Figure 4B). We hypothesized that this effect on mISPC amplitude may have been due to an overestimation of the mIPSC amplitude under conditions of high mIPSC frequency, when superimposed mIPSCs may not always be detectable.

As pharmacological approaches commonly used to differentiate the two subunits are limited at best, the authors used genetic manipulations to engender chimeric receptors in which only the CTD from GluN2A Osimertinib in vitro and GluN2B receptor subunits is C-terminal replaced (CTR). Why focus on the CTD? It has been shown that the CTD of NMDAR subunits is the primary area of sequence divergence, and it is the site that primarily

binds scaffolding proteins, providing a strong rationale for examining its role in excitotoxicity. In the first series of experiments, expression of chimeric GluN2B2A(CTR) receptors in transfected hippocampal neurons produced similar currents as wild-type (WT) subunits (GluN2BWT) and did not affect the proportion of synaptic and extrasynaptic receptors, thus preventing potential confounds arising

from receptor location. Interestingly, NMDA-induced cell death was reduced in chimeric GluN2B2A(CTR) compared to GluN2BWT-containing receptors, suggesting that excitotoxicity is better promoted by CTD2B than CTD2A. Similarly, neurons expressing GluN2A2B(CTR) LY294002 datasheet were more susceptible to cell death than neurons expressing GluN2AWT (Figure 1). Using a different approach, a knockin mouse was generated in which the protein-coding region of the C-terminal exon of the GluN2B subunit was exchanged for that of the GluN2A subunit, named GluN2B2A(CTR)/2A(CTR). Cultured cortical neurons from these mice displayed

similar levels of viability, synaptic connectivity, proportion of extrasynaptic NMDARs, sensitivity to ifenprodil, rundown of NMDA currents, and single channel conductance, compared to those from GluN2B+/+ mice. Notwithstanding these similarities, NMDA currents were about 30% lower in GluN2B2A(CTR)/2A(CTR) than in GluN2B+/+ cells. By adjusting exogenous NMDA concentrations to produce similar currents in both types of cells, the authors confirmed that normalized NMDA current produced more death in GluN2B+/+ than in GluN2B2A(CTR)/2A(CTR) cells. In consequence, a switch in the mouse genome from GluN2B CTD for GluN2A reduces NMDA-dependent Ca2+ influx Isotretinoin and excitotoxicity. However, these differences only occurred at moderate (15–50 μM) NMDA concentrations. When NMDA concentration was increased (e.g., 100 μM), the CTD subtype-specific vulnerability disappeared. These results were confirmed in vivo. Thus, excitotoxic lesions induced by stereotaxic injection of a small dose of NMDA into the hippocampus (CA1-CA3 region) induced smaller lesion volumes in GluN2B2A(CTR)/2A(CTR) compared to GluN2B+/+ mice. Which signaling cascades contribute to differential susceptibility of CTDs to excitotoxic insults? One obvious target, based on previous work by Hardingham’s and other groups, is NMDA-dependent activation of CREB.

, 2010, Farrant and Cull-Candy, 2010 and Guzman and Jonas, Selleckchem Antidiabetic Compound Library 2010) ( Table 1). What consequences

might the unique properties of CKAMP44 have on hippocampal function? To discern this, the authors used overexpression of CKAMP44 in combination with CKAMP44 KO mice. They first examined CA1 pyramidal neurons, which express low levels of CKAMP44. They show that overexpression slows the decay of mEPSCs and reduces PPR, consistent with the slowing of recovery from desensitization. Interestingly, in contrast to the effects of overexpression, the CKAMP44 KO has no effect on EPSC kinetics, as might be predicted by the low expression level. The authors repeated these experiments in dentate granule neurons where CKAMP44 is expressed at high levels. Overexpression of CKAMP44 has no effect on PPR, but

in the KO, PPR is enhanced. It would be of interest to know whether the decay of EPSCs in KO granule neurons is accelerated as would be expected. These findings are of considerable interest because, except for a few types of synapses where the probability of release is high and/or multiple active zones are present, desensitization is not thought to play a prominent role in PPR (Silver and Kanichay, 2008). How widespread might the role of CKAMP44 in the CNS be? CKAM44 expression is especially high in the dentate gyrus compared to many other regions of the brain, raising the possibility find more that its role could be more restricted than that of TARPs. It is not clear what Olopatadine advantage may be conferred by having TARPs and CKAMP44 interacting with the same AMPAR, given that their actions are antagonistic, at least in terms of their effects on desensitization. Synapse differentially induced

gene 1 (SynDIG1) is a candidate AMPAR auxiliary subunit that was identified through application of a microarray approach to the expression profile of the cerebella of lurcher mice, which show defects in neuronal differentiation. One of the most highly differentially expressed genes was SynDIG1 ( Díaz et al., 2002), which is upregulated during postnatal development in wild-type, but not lurcher, cerebella. SynDIG1 is a type II transmembrane protein that regulates AMPAR content at developing hippocampal synapses ( Kalashnikova et al., 2010). Immunocytochemical experiments in cultured hippocampal neurons show that, while SynDIG1 clusters at excitatory synapses, most clusters are nonsynaptic, but are nonetheless associated with GluA2, suggesting that it might bind to GluA2. Indeed, anti-SynDIG1 antibodies coimmunoprecipiate GluA2 from brain extracts and the two proteins cluster on the surface of heterologous cells. This clustering requires an intact extracellular C terminus of SynDIG1. Overepression of SynDIG1 increases synapse density and increases the size and fluorescent intensity of GluA1 puncta, but not NR1 puncta.

Remarkably, by the age of 75 years, more than half of the functional capacity of the CV system has been lost,8 leading to VO2max values lower than that which is required for many common activities of daily

living.9 More than just leading to decreases in quality of life, low cardiorespiratory fitness has been associated with CV disease and all-cause mortality.10, 11 and 12 The CV system remains adaptable at any age,13 and 14 with relative increases in VO2max in older populations equivalent to those seen in younger individuals. Physical activity (PA) has long been associated with the attenuation of physical decline associated with aging.15 The purpose of this article is to: 1. Examine the decline in physiological variables associated with aging and a sedentary lifestyle. Aging is associated with physiological declines, notably a decrease in BMD and lean body mass (LBM),

with a concurrent increase Selleckchem GSK3 inhibitor see more in body fat and central adiposity.16 and 17 It is possible that the onset of menopause may augment the decline in physiological decline associated with aging and inactivity.5 Wang and colleagues18 compared almost 400 early postmenopausal women and found higher levels of total body fat, as well as abdominal and android fat in postmenopausal women. Consequently, the authors could not conclude that the changes in body fat were related to menopause or merely a result of aging alone. Levetiracetam The authors did note, however, that changes in fat-free mass (FFM), including bone mass, may be attributed to menopause-related mechanisms, including deficiencies in growth hormones and estrogen. Douchi et al.5 had similar findings when comparing body composition variables between pre- and post-menopausal women. The authors demonstrated an increase in percentage of body

fat (30.8% ± 7.1% vs. 34.4% ± 7.0%), trunk fat mass (6.6 ± 3.9 kg vs. 8.5 ± 3.4 kg), and trunk–leg fat ratio (0.9 ± 0.4 vs. 1.3 ± 0.5) with aging. Concurrently, they found that lean mass (right arm, trunk, bilateral legs, and total body (34.5 ± 4.3 kg vs. 32.5 ± 4.0 kg)) also declined with age. Baker and colleagues 19 found that females had a greater decline in BMD with age compared to males. More so, a higher incidence of metabolic syndrome (an accumulation of cardiovascular disease risk factors including obesity, low-density lipoprotein cholesterol (LDL-C), high blood pressure, and high fasting glucose) has been shown in middle-aged women during the postmenopausal period. This is due in part to the drastic changes in body composition, as previously discussed, but also a change in PA levels. In a longitudinal study of over 77,000 (34–59 years) women spanning 24 years, van Dam et al. 20 found high body mass index (BMI, 25+) and lower levels of PA (<30 min/day of moderate to vigorous intensity activity) to be attributed with a higher risk of CV disease, cancer, and all-cause mortality. Furthermore, Sisson et al.

Despite the increased popularity and professionalization of women’s football around the world, there is still limited scientific research specific to female players compared to their male counterparts, especially in the areas of players’ physical and physiological characteristics and game demands. For instance, in the case of men’s football, there are numerous full-text peer-reviewed studies that have been published on these topics including players of several nationalities, competitive

DAPT clinical trial levels, age groups, and playing positions. Additionally, several comprehensive literature reviews have been published in order to discuss and summarize the findings of a large number of studies in this area.4, 5, 6, 7, 8, 9, 10, 11 and 12 In women’s football, on the other hand, only one journal review article dealing specifically with the applied physiology of female soccer (football) players was found in the present literature review.13 This review article was published about 20 years Dasatinib ago, when women’s football

was still in its infancy and there were only a few published studies to report on. More recently, a book chapter with specific focus in reviewing the game and training demands of senior elite female football players has been published.14 However, information on female football players of lower competitive levels and younger age groups was not included. The number of scientific publications specific to player characteristics and game demands in women’s football has noticeably grown since then including information of players of several nationalities, competitive levels, age groups, and playing positions.15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,

49, 50, 51, 52, 53, 54, 55, 56, 57, mafosfamide 58, 59, 60, 61, 62, 63, 64, 65 and 66 Consequently, an updated review is needed in this area. Therefore, the purposes of the present literature review are: 1) to provide an overview of a series of studies that have been published so far on the specific characteristics of female footballers and the demands of match-play; 2) to identify areas/topics that require further scientific research in women’s football; and 3) to derive a few practical recommendations from the information gathered in this review. Knowledge and understanding of this information can help coaches and sport scientists to design more effective training programs and science-based strategies for the further improvement of players’ football performance, health, game standards, and positive image of the women’s game.

For instance Obeticholic Acid cell line activation of glutamate receptors (Beattie et al., 2000 and Ehlers, 2000) or increasing neural network activity by membrane depolarization or by unbalancing excitatory and inhibitory inputs to favor excitation (Lin et al., 2000) result in reductions in synaptic receptor accumulation through receptor internalization, whereas selective activation of synaptic NMDARs leads to facilitated AMPAR recycling and membrane insertion (Lu et al., 2001, Man et al.,

2003 and Park et al., 2004). Trafficking-dependent alterations in AMPAR synaptic localization serve as a primary mechanism not only for the expression of Hebbian-type synaptic plasticity (Malenka, 2003, Malinow and Malenka, 2002, Man et al., this website 2000a and Song and Huganir, 2002) but also for the expression of negative feedback-based homeostatic synaptic regulation (Lévi et al., 2008, Sutton et al., 2006, Turrigiano and Nelson, 1998 and Wierenga et al.,

2005). Ultimately, total receptor abundance is determined by a balance between receptor synthesis and degradation. At basal conditions, AMPARs have a half-life of about 20–30 hr (Huh and Wenthold, 1999 and Mammen et al., 1997). Molecular details and signaling pathways involved in AMPAR turnover have not been well studied, but both lysosomal and proteasomal activities have been implicated in AMPAR degradation (Ehlers, 2000, Lee et al., 2004 and Zhang et al., 2009). Enhanced AMPAR degradation is often observed following receptor ubiquitination and internalization (Lin et al., 2011, Lussier et al., 2011 and Schwarz et al., 2010), and under certain circumstances receptor internalization

is a prerequisite for degradation (Zhang et al., 2009). Furthermore, AMPARs can be synthesized locally in dendrites and spines from locally distributed receptor subunit mRNAs and protein synthesis machinery (Grooms second et al., 2006 and Sutton et al., 2004). Presumably, local AMPAR degradation in the spine might also occur, thereby enabling a rapid, synapse-specific adjustment in receptor abundance (Fonseca et al., 2006, Hegde, 2004, Segref and Hoppe, 2009 and Steward and Schuman, 2003). A central neuron receives thousands of inputs from presynaptic neurons distributed in a wide range of locations in the brain with varied levels of basal activity. Thus, the intensity of synaptic inputs at a neuron differs from one another, and changes from time to time depending on the cell type and local circuitry of each presynaptic neuron. Homeostatic regulation has been found to occur on the scale of neuronal networks, individual neurons (Burrone et al., 2002, Goold and Nicoll, 2010 and Ibata et al., 2008), or subcellular dendritic regions (Yu and Goda, 2009); but whether it is employed at the single synapse level, crucial in our understanding of synaptic plasticity and neuronal computation as well as higher brain function, remains to be investigated.

To explore the function of FXR2 in adult neurogenesis, we assessed the proliferation and differentiation of NPCs in Fxr2 KO mice and wild-type (WT) controls using a saturation BrdU pulse-labeling method that could label the entire pool of proliferating NPCs within a 12 hr period ( Figure 2A) ( Hayes and Nowakowski, 2002 and Luo et al., 2010). Quantitative analysis at 12 hr following the last BrdU injection showed that, in the DG of the hippocampus, Fxr2 KO mice had ∼20% more BrdU+ cells compared

with WT littermates ( Figures 2B and 2C; n = 6, p < 0.05). Nestin+ immature cells in the DG are known to contain at least two populations: Nestin+GFAP+ radial glia-like cells (also called type 1; Figure 2D) and Nestin+GFAP− nonradial glia-like cells (also called type http://www.selleckchem.com/products/ipi-145-ink1197.html 2a; Figure 2G). Both types can incorporate BrdU ( Ables et al., 2010, Kempermann et al., 2004 and Ming

and Song, 2005). In the Fxr2 KO DG, both total Nestin+ cells (n = 6, p < 0.001) and Nestin+GFAP+ radial glia-like NPCs ( Figures 2E and 2F; n = 6, p < 0.001) exhibited increased BrdU incorporation, whereas Nestin+GFAP− nonradial glia-like NPCs did not ( Figure 2H; n = 6, p = 0.7313). The volume (size) of the DG did not differ between WT and Fxr2 KO mice (data not shown). These results indicate that FXR2 deficiency leads to increased proliferation of radial glia-like NPCs in the adult DG. We next assessed the fate of new cells in the DG at one week after BrdU injection. We found that FXR2-deficient mice still had ∼25% selleck products more BrdU+ cells (Figures 2B and

2C; n = 5, p < 0.05) and that the survival rate of BrdU+ cells from 12 hr to one week after BrdU injection was no different between WT and Vasopressin Receptor Fxr2 KO mice (n = 6, p = 0.99). On the other hand, BrdU+ cells in the Fxr2 KO DG differentiated into more DCX+ neurons compared with WT mice ( Figures 2I and 2J; n = 6, p < 0.001). Therefore, FXR2 deficiency leads to enhanced proliferation and neuronal differentiation of NPCs in the DG, without affecting the short-term survival of new cells. We then assessed neurogenesis in the SVZ of adult Fxr2 KO mice. To our surprise, Fxr2 KO mice showed no significant differences in BrdU incorporation ( Figure 2K; n = 5, p = 0.525) and the proliferation of either Nestin+GFAP+ cells ( Figure 2L; n = 6, p = 0.6472) or Nestin+GFAP− cells (n = 6, p = 0.8538) compared to WT mice. Furthermore, at one week after BrdU injection, the percentage of DCX+ neuroblasts among BrdU+ cells in the rostral migratory stream (RMS, Figure 2M) was essentially the same for WT and Fxr2 KO mice (n = 5, p = 0.8871). Taken together, these results suggest that the loss of FXR2 specifically alters neurogenesis in the adult DG, but not in the adult SVZ.