,

1998; Shepherd et al., 2004; Yokoi et al., 1995). However, the direct measurement of granule cell activity in vivo has been limited to a few studies performed in anesthetized animals (Cang and Isaacson, 2003; Tan et al., 2010), hampering our understanding of the operation of olfactory bulb inhibitory interneurons in the awake state. Attempts to estimate the effect of anesthesia on granule cell activity with extracellular recording of field potentials (Nicoll, 1972; Stewart and Scott, 1976; Tsuno et al., 2008) have reached inconsistent conclusions, reflecting the difficulty of interpreting these indirect measurements. Here we report, to our knowledge, the first direct in vivo measurements of granule cell activity in awake animals. Granule cells respond to odors rapidly, and their tuning properties are similar to those of mitral cells. Strikingly, anesthesia caused a substantial attenuation learn more of both spontaneous and odor-evoked granule cell activity, which is in stark contrast to the enhancement of odor-evoked activity of mitral cells in the anesthetized state.

The reduction of granule cell activity in the anesthetized state is consistent with previous intracellular recordings under anesthesia, which reported a low probability of odor-evoked action potentials in granule cells (Cang and Isaacson, 2003) and indicates that granule cell recordings under anesthesia HSP inhibitor have underestimated their actions in the awake state. We think it is unlikely that the anesthetics

are directly changing the intrinsic excitability of granule cells, since the two chemically distinct anesthetics (ketamine and urethane) had the same effect on granule cell activity. Rather, the effect of the anesthetics is likely to reflect modulation of brain state. For example, granule cells are a major target of centrifugal input Ellagic acid originating from the olfactory cortex (de Olmos et al., 1978; Haberly and Price, 1978), which could be sensitive to the state of the animal (Murakami et al., 2005). Taken together, our results suggest that wakefulness greatly enhances the impact of inhibitory circuits on olfactory bulb odor representations. We envision that the sparsening and richer temporal dynamics of mitral cell odor representations we observed in the awake state may be a result of shaping by active inhibitory circuits. It will be interesting to determine whether wakefulness also enhances the activity of interneurons in other brain regions. We showed that repeated brief odor experience leads to a modification of mitral cell activity that accumulates across days and persists for over a month. Hence, experience-dependent plasticity in the olfactory bulb is not just a transient adaptation to continuous odor stimuli, but rather a process that integrates months of odor experience.

These noncanonical input structures would need more evidence to conclusively demonstrate the existence BMS-354825 mouse of these connections. We built brain-wide maps of inputs to the two main projection

cell types in striatum, discovering both striking similarities and notable differences in the patterns of synaptic input to the direct or indirect pathway that were not observable using standard anatomical approaches. Cortical and limbic structures provided biased proportions of synaptic input to the two basal ganglia pathways, whereas individual cortical layers, thalamic nuclei, and dopaminergic input were largely equivalent across the two classes of striatal MSN. By using genetic tools to segregate the inputs to D1R and D2R-expressing MSNs, we demonstrated that information segregation into the basal ganglia occurs before the level of the striatal medium spiny neuron, and that different brain structures vary in degree to which they preferentially innervate specific

target cell classes in the striatum. The specific roles of the direct and indirect pathways in behavior have been debated for decades, and identification of the sources of synaptic inputs selleck compound to these circuits may provide fresh insight into their function. Classical models of the basal ganglia have suggested that the direct pathway facilitates, whereas the indirect pathway suppresses, movements Non-specific serine/threonine protein kinase and actions (Albin et al., 1989 and DeLong, 1990), yet their roles are surely more complex than this. Modeling and evidence from reinforcement paradigms suggest that, within specific contexts, the direct pathway may facilitate previously-rewarded actions, whereas the indirect pathway may suppress previously-unrewarded actions (Bromberg-Martin et al., 2010, Frank et al., 2004, Hikida et al., 2010 and Kravitz et al., 2012). Such a scheme relies on an integration of motor, sensory, and reward information, yet little is known about how this information is relayed

to the basal ganglia or how it might affect specific cell types (Fee, 2012). Dopamine is hypothesized to oppositely act on direct- and indirect-pathway MSNs via distinct signaling through Gs-coupled D1 and Gi-coupled D2 receptors (Gerfen et al., 1990), but differential actions of motor and sensory afferents on MSN subtypes has not, to our knowledge, been proposed. Here, we find differential innervation of indirect-pathway MSNs by motor cortex afferents, whereas inputs transmitting contextual information (sensory/limbic) preferentially innervate direct-pathway MSNs. This architecture suggests a model of basal ganglia function in which action information (e.g., efference copy) is differentially transmitted to the indirect pathway, potentially to suppress competing actions, or to prime the animal to switch to the next step in an action sequence.

25, p = 0.036), and the transverse temporal region (t[21] = 2.79, p = 0.011). Accumbens favored win information, showing significant win-tie decoding (55% accuracy, on average, t[21] = 3.77, p < 0.001) but not tie-loss (51% average accuracy, t[21] = 1.17, p = 0.13). Caudal ACC also favored win-tie over tie-loss discriminations (56% versus 52% accuracy), but still showed a significant (p < 0.05, uncorrected) tendency to decode tie-loss (t[21] = 1.74, p = 0.048). Transverse temporal region showed an ability to decode tie versus loss

information (t[21] = 3.21, p = 0.002) but not win versus tie (t[21] = −0.28, p = 0.6). In a similar searchlight analysis, we contrasted the ability of each voxel to decode wins-ties and ties-losses. We found eight small clusters that differed significantly in their learn more ability to perform these two classifications (Table S6; figures not shown because these small clusters did not show up well when projected to the surface). Regions that did better on win-tie than tie-loss (p < 0.001, k = 10) were in the right basal ganglia (medial globus pallidus), find protocol the left ACC, and left middle frontal gyrus. Regions performing better

on ties-losses were the left amygdala and regions in the right IPL, left medial temporal, left fusiform and left middle temporal gyrus. In total, clusters showing these differences only encompassed 136 voxels, far fewer than those with significant three-way win-tie-loss classification (equal to only 0.4% of the number of voxels able to decode win-tie-loss). Of 34,520 above-chance voxels in three-way win-tie-loss classification, only 25 voxels showed a significant difference between win-tie and tie-loss classification

(42 without cluster correction). Therefore, signals related to both reinforcements and punishments were remarkably ubiquitous, and there was very little difference between encoding of the two. The addition of tie outcomes in Experiment 2 afforded the ability to distinguish signals related to reinforcement and punishment from those related to salience. One possible explanation for the ubiquitous reward signals in Experiment 1 is that one of the two outcomes heptaminol in the matching pennies game is more attention-demanding or salient (Maunsell, 2004, Bromberg-Martin et al., 2010, Chun et al., 2011 and Litt et al., 2011). By contrast, during rock-paper-scissors, the “tie” outcome should be less salient and arousing than both wins and losses. We evaluated the salience hypothesis by using a pair of classifiers. First, we trained classifiers to discriminate wins from ties (win-tie classifier), then evaluated whether they tended to classify unseen losses as wins or ties. Next, we also trained classifiers to discriminate ties from losses (tie-loss classifier), then evaluated whether they tended to classify unseen win trials as ties or losses.

, 2011). During depolarized (but not hyperpolarized) cortical states, the optogenetic stimulus also strongly drove APs in 5HT3AR neurons, demonstrating brain state-dependent recruitment of different inhibitory cell types. Strong disynaptic inhibition

mediated by PV and 5HT3AR GABAergic neurons therefore apparently drives competition for action potential firing among excitatory L2/3 neurons. Inhibition also strongly limits the sensory-evoked discharge of L2/3 neurons in the visual cortex of awake mice (Figure 4C) (Haider et al., 2013). Interestingly, this later study points to an important difference in the balance between excitation and Veliparib solubility dmso inhibition in awake compared to anesthetized animals, with more prominent inhibition during wakefulness. It will therefore be important in the future to further investigate the contribution of inhibition to sculpting the neural code in awake animals. In order to obtain a mechanistic Capmatinib research buy understanding

of neocortical function, it will be essential to characterize the synaptic wiring diagram of the neuronal networks, as well as the activity of the neurons during behavior. The synaptic connectivity between nearby neurons within local neocortical microcircuits has so far been studied ex vivo in brain slices and, here, we will focus on current knowledge of cell type-specific patterns of excitatory and inhibitory synaptic connectivity

within neocortical L2/3. Comparison of the connectivity of excitatory and inhibitory neurons in L2/3 has consistently shown that excitatory neurons are sparsely connected to each other with weak synapses on average, whereas synaptic interactions between excitatory and inhibitory neurons are dense and strong. Holmgren et al. (2003) probed synaptic connectivity between excitatory pyramidal neurons and fast-spiking PV-expressing GABAergic neurons through whole-cell recordings in L2/3 of rat somatosensory and visual cortex, estimating that excitatory neurons within a 100 μm radius were connected to each other with ∼5% probability and average unitary excitatory postsynaptic potential (uEPSP) amplitude of 0.7 mV, whereas excitatory neurons innervated PV neurons mafosfamide with 78% connection probability and uEPSP amplitude of 3.5 mV. In L2/3 of mouse barrel cortex, Avermann et al. (2012) probed synaptic connectivity with multiple simultaneous whole-cell recordings between GFP-labeled GABAergic neurons and excitatory pyramidal neurons, finding that excitatory neurons connect to each other with probability of 17% with average uEPSP amplitude of 0.4 mV, that excitatory neurons innervate PV neurons with probability of 58% and mean uEPSP amplitude of 0.8 mV, and that excitatory neurons innervate 5HT3AR neurons with 24% connection probability and 0.4 mV mean uEPSP amplitude (Figures 5A and 5B).

, 2011 and Radley et al., 2008), with the most extensive spine loss occurring in the distal portion of the dendritic arbor. The spines that are most vulnerable to stress are the thin spines, and this selective vulnerability of thin spines has implications Talazoparib clinical trial for plasticity and cognitive performance, discussed below. While these morphologic effects are quite dramatic, perhaps even more surprising is that the neurons recover

in the absence of stress, i.e., with a rest period of 3 weeks (Bloss et al., 2011 and Radley et al., 2005). In young animals, the dendritic arbor fully recovers and spine density partially recovers in the absence of stress (Bloss et al., 2011). It appears that such structural recovery is accompanied by functional recovery, at least in the case of layer 5 neurons in IL. As with layer 3 neurons, chronic stress induced dendritic shrinkage in layer 5 neurons and they recovered with a rest period. However, the recovery occurred primarily in the proximal dendrites, such that the stress and recovery sequence shifted the overall geometry of the neurons to a distal arbor-reduced and proximal arbor-expanded configuration (see Figure 2B). However, this shift in geometry did not preclude functional recovery as reflected by D1R-mediated modulation of LTP on layer 5 neurons. The capacity of D1R activation to increase

the amplitude of potentiation was decreased Atezolizumab datasheet by chronic stress yet was fully restored

with a poststress recovery period (Goldwater et al., 2009). It is particularly interesting that such functional recovery occurred against the background of an altered overall dendritic geometry in neurons that have undergone a stress and recovery sequence (Goldwater et al., 2009). The degree to which the altered morphology affects other functional attributes, synaptic connectivity, or future capacity for recovery needs to be fully Masitinib (AB1010) investigated. Along with many other brain regions, the amygdala and prefrontal cortex also contain adrenal steroid receptors (Ahima et al., 1991 and Ahima and Harlan, 1990) and excitatory amino acids appear to play a role in stress-induced dendritic retraction (Martin and Wellman, 2011). Furthermore, effects of 21 days of chronic restraint stress on working memory and dendritic shrinkage and spine loss were prevented by inhibition of PKC (Hains et al., 2009). As to the role of glucocorticoids, 3 weeks of chronic corticosterone treatment was shown to produce retraction of dendrites in medial prefrontal cortex (Cerqueira et al., 2005 and Wellman, 2001), although with subtle differences in the qualitative nature of the effect from what has been described after chronic restraint stress. Other studies confirm a role of adrenal steroids in the mPFC using adrenalectomy and steroid administration.

The gene expression profile of some of these cells will be sufficient to endow this subpopulation with the properties required ATM/ATR inhibitor for local invasion, survival in the circulatory system, extravasation into secondary organs, and growth as overt metastases at these sites. Other subpopulations of cells in the primary tumor will have some of the properties required, but will not successfully complete all the necessary

steps. Thus tumor cells that successfully form metastases should be considered as “decathlon winners” [10]. In addition to experimental evidence from animal models, support for the clonal selection theory comes from histological and genetic analysis of human tumors which provides evidence for heterogeneous patterns of gene expression

[11]. A corollary of the clonal selection theory is that organ-specific patterns of metastasis may be dependent on tumor-intrinsic properties that are selected for as tumor cells disseminate. Initial evidence for the existence of genes driving organ-specific metastasis came from the identification of poor prognosis gene signature through supervised clustering of cohorts of primary breast cancers [12], [13], [14] and [15]. Subsequently, gene expression signatures associated with breast cancer metastasis to bone, lung and brain were defined in experimental models and validated with human samples [16], [17] and [18]. These experimental studies were based on the generation and analysis of organotropic metastatic lines derived from a parental line (mostly MDA-MB-231) by multiple rounds of Dabrafenib in vivo selection. The brain and lung metastasis signature were partly

overlapping and contained genes controlling vascular remodeling and permeability, such as COX2, ANGPTL4, LTBP1 and EGFR ligands. The bone metastasis signature was rather divergent, and contained genes associated with bone osteolysis and cell survival in the bone such as IL-11, PTHrP and OPN. Besides allowing the identification of individual genes, these studies proved PTK6 useful for the classification of metastasis-promoting genes based on their functional contribution to metastasis. Three categories were defined: (i) metastasis-initiating genes, comprising genes that provide an advantage in tumor cell growth, escape and invasiveness at the primary tumor site; (ii) metastasis virulence genes, giving survival advantages to disseminated tumor cells within the newly colonized microenvironment; (iii) genes promoting progression, giving advantages during the entire metastatic process by affecting general steps, such as tumor angiogenesis, inflammation, epithelial–mesenchymal transition (EMT), or immune evasion. While these studies have provided unprecedented molecular details on the mechanisms of organ-specific metastasis, many questions that are relevant for the development of therapeutic strategies remain open.

Research in E.Y.I.’s laboratory is supported by the NIH (R01NS035549) and NSF (FIBR 0623527). This work was funded by a European Research Council Starting Independent Researcher Grant to R.B. “
“Cortical GABAergic interneurons are generated in multiple progenitor zones of the subpallial (subcortical)

telencephalon, including the lateral, medial, and caudal ganglionic eminences (LGE, MGE, and CGE) (Anderson Vemurafenib et al., 1997a, Anderson et al., 2001, Butt et al., 2005, Fogarty et al., 2007, Marin and Rubenstein, 2003, Pleasure et al., 2000, Sussel et al., 1999 and Wonders and Anderson, 2006). The specification, differentiation, and migration of these cells are regulated by multiple transcription factors, including the Dlx1,2,5,6 and Lhx6 homeobox genes. The Dlx genes are critical for interneuron migration and differentiation. For example, mice lacking Dlx1/2 show a block in the migration of most cortical and hippocampal interneurons ( Anderson et al., 1997a and Pleasure et al.,

2000). Mice lacking Dlx1 show defects in dendrite-innervating interneurons ( Cobos et al., 2005), whereas mice lacking either Dlx5 or Dlx5/6 have defects in somal-innervating (parvalbumin+; PV+) interneurons ( Wang et al., 2010). Studies on transcriptional alterations in the Dlx1/2–/– mutants have begun to elucidate the molecular pathways that regulate interneuron development and

function ( Long et al., 2009a and Long et al., 2009b). We have discovered that the Dlx genes promote the expression of two chemokine receptors, CXCR4 and CXCR7 (RDC1; CMKOR1) ( Long et al., Osimertinib in vitro 2009a, Long et al., 2009b and Wang et al., 2010). Furthermore, these receptors are also positively regulated by the Lhx6 transcription factor ( Zhao et al., 2008) that is essential for the differentiation of PV+ and somatostatin+ (SS+) interneurons PFKL ( Liodis et al., 2007 and Zhao et al., 2008). CXCR4 and CXCR7 are seven-transmembrane receptors that bind CXCL12, a chemokine also known as Stromal-derived factor 1 (SDF1) (Balabanian et al., 2005 and Libert et al., 1991). CXCL12 binding to CXCR4 triggers Gαi protein-dependent signaling, whereas CXCl12 binding to CXCR7 does not activate Gαi signaling (Levoye et al., 2009 and Sierro et al., 2007). On the other hand, many lines of evidence indicate that CXCR7 has an important role in regulating cell signaling in culture and in vivo. In developing zebrafish, CXCR4 and CXCR7 are both implicated in regulating migration of primordial germ cells (PMGs) and the posterior lateral line primordium, in part through their differential expression patterns (Boldajipour et al., 2008, Dambly-Chaudiere et al., 2007 and Valentin et al., 2007). For instance, while CXCR4 is expressed in the germ cells, CXCR7 is expressed in adjacent cells.

, 2011); and mouse anti-V5 (Invitrogen, 1:500). For immunofluorescence analyses, the following secondary antibodies were used: goat anti-mouse, rabbit, and rat F(ab′)2 fragments coupled to FITC (1:200), Cy3/DyLight549 (1:400) or Cy5/DyLight649 (1:200) (Jackson ImmunoResearch STAT inhibitor Laboratories), as well as goat anti-mouse Alexa Fluor 568 (1:400; Invitrogen). As the V5 epitope was detectable using

anti-V5 antibody in western blots but not in cells or tissues, NetB was visualized using anti-NetB antibody. Images were collected using Zeiss/Bio-Rad Radiance2100, Leica TCS SP5II, and Zeiss LSM710 laser-scanning confocal microscopes. Immunofluorescence levels were determined using ImageJ; neurons were traced using Fiji Simple Neurite Tracer. For stainings shown in supplemental figures, see Supplemental Experimental Procedures. Detailed staining protocols are available upon request. We thank B. Altenhein, M. Brankatschk, B.J. Dickson, T. Hummel, C.H. Lee, R. Ueda, J.P. Vincent, the Bloomington Drosophila Stock Center, the Drosophila Genomics Resource Center, the Vienna Drosophila RNAi Center, the Kyoto Drosophila Genetic Resource Center, the National Institute of Genetics Fly Stock Center, and the Developmental Studies Hybridoma Bank for fly strains, antibodies, and plasmids. We thank C. Desplan for sharing lGMR-Gal80 transgenic flies and H. Apitz, C. Chotard, L. Ferreira, and Z. Ludlow for contributions

to the MH-Gal4 screen. We are grateful to F. Guillemot, E. Ober, J.P. Vincent, as well as H. Apitz, D. Brierley, E. Richardson, B. Richier, and N. Shimosako for critical reading of the manuscript.

This work is supported by a Marie Sorafenib cell line Curie Intra-European Fellowship (to W.J.) and the Medical Research Council (U117581332). “
“Brain functions are made possible by synapses, contacts formed between neurons or between a neuron and a target cell. The neuromuscular junction (NMJ) is a cholinergic synapse between motoneurons and skeletal muscle fibers that has most, if not all, features characteristic of a chemical synapse in the brain. Because of its simplicity, high spatial resolution, and accessibility, the NMJ has served as an informative model of synaptogenesis (Sanes and Lichtman, 1999, Sanes and Lichtman, 2001 and Wu et al., 2010). Its development requires the precise coordination between presynaptic Procainamide motoneurons and postsynaptic muscle fibers. Mechanisms by which motoneurons instruct postsynaptic differentiation are better characterized, whereas relatively little is known about retrograde signals from the muscle fibers. Agrin is a nerve-derived organizer of postsynaptic differentiation during NMJ formation (McMahan, 1990). It stimulates AChR cluster formation in myotubes in culture (Ferns et al., 1993 and Nitkin et al., 1987) and mice lacking agrin do not form the NMJ (Gautam et al., 1996). MuSK is a receptor tyrosine kinase that is essential for agrin-induced clustering and for NMJ formation in vivo (DeChiara et al., 1996, Glass et al.

The GLM, however,

attempts to fit the spatial firing rate map of the neuron to a function with five parameters (see Experimental Procedures, Equation 4). We found a strong correlation between the difference score and the deviance of the “S” ON-1910 model from the full model (Pearson’s linear correlation coefficient: 0.49; p = 2 × 10−24) (Figure S5B) indicating that the results from these two methods agree with one another, and the finding that hippocampal activity during treadmill running cannot be explained by spatial position does not depend upon the assumptions made by either model. As noted previously, it is impossible to completely separate time and distance as long as the rat is running on the treadmill, and the results from analyzing the “S” model refer to the combined influences of time and distance. However, the randomized treadmill speed did allow us to also consider the components of time and distance that were independent from one another. The space and time (“S+T”) and space and distance (“S+D”) nested models allowed us to determine the influence on the model fit of adding information about distance to a model that already included time (“S+T” versus “S+T+D”) or adding time to a model

that already included distance (“S+D” versus “S+T+D”) to show the independent effects of each variable. This analysis indicated that distance (in addition to time and space) PLX4032 price was informative in 314/400 neurons (79%, χ25 > 11.1, p ≤ 0.05),

while time (in addition to distance and space) was informative in 326/400 neurons (82%, χ25 > 11.1, p ≤ 0.05) (Figure 8A). Both distance and time were independently informative in 284 neurons (70%), while neither distance nor time were independently informative in 44 neurons (11%). Of particular note are 42 neurons (11%) that showed distance but not time as informative, and 30 neurons (8%) that showed time but not distance as informative (Figure 8A). These results demonstrate that while the majority of neurons were influenced by both time and distance, individual neurons varied in their degree of tuning to either time or distance. At the extremes of this distribution, some neurons Oxygenase exclusively signaled time and other neurons exclusively signaled distance. For all 356 neurons that showed a significant contribution of either time or distance, we subtracted the deviance of the “S+T” model from the deviance of the “S+D” model to obtain a measure of the tuning of each neuron for either time or distance. Values greater than zero indicate a stronger tuning to time whereas values less than zero indicate a stronger tuning for distance. Using this metric, 220/356 neurons (62%) were more tuned to time and the remaining 136 neurons (38%) were more tuned to distance (Figure 8B).

Early passage primary NPCs isolated from both DG and SVZ were positive for the progenitor markers Nestin and Sox2 ( Figure 3B) and expressed FXR2 ( Figure S2A and S2B). Cobimetinib in vitro In fact, 96.7% ± 0.84% of total cultured NPCs and 98.8% ± 0.82% of Nestin+Sox2+ NPCs expressed FXR2 ( Figure S2C). We found that Fxr2 KO DG-NPCs exhibited significantly higher BrdU incorporation compared with WT cells, particularly in the Sox2/Nestin double-positive populations ( Figures 3C and 3D; n = 3, p < 0.05).

In addition, DG-NPCs isolated from Fxr2 KO brains yielded ∼25% more primary neurospheres that were ∼40% larger (in diameter) than WT controls ( Figures 3E–3G; n = 3, p < 0.001). To determine the self-renewal capability of these neurospheres, primary spheres were individually Selleck INK1197 dissociated into single cells and plated at clonal

density. Fxr2 KO DG-NPCs yielded ∼40% more secondary and tertiary spheres with ∼30% increased size compared to WT cells ( Figures 3H and 3I; n = 3, p < 0.001). These results indicate that FXR2 deficiency leads to increased proliferation and self-renewal of DG-NPCs. However, SVZ-NPCs derived from WT and Fxr2 KO mice ( Figure 3J) had the same BrdU incorporation rate (n = 3, p = 0.8268) and displayed the same primary neurosphere formation as well as similar self-renewal abilities (n = 3, p > 0.05; Figures S2D–S2F). Therefore, FXR2 deficiency does not affect the self-renewal of SVZ-NPCs. Consistent with our in vivo findings, Fxr2 KO DG-NPCs exhibited a ∼30% increase in neuronal differentiation ( Figures 4A and 4B; n = 3, p < 0.001) and a ∼60% decrease in astrocyte differentiation ( Figures 4D and 4E; n = 3, p < 0.001) compared with WT controls. The PRKACG reduction in astrocyte differentiation

was not a result of increased death of GFAP+ astrocytes ( Figures S2G and S2H). To validate our immunocytochemical data, we assessed differentiation of NPCs by measuring the promoter activity of a pan-neuronal transcription factor, Neurogenic differentiation 1 (NeuroD1) and the promoter activity of astrocyte GFAP ( Liu et al., 2010 and Luo et al., 2010). In Fxr2 KO DG-NPCs, NeuroD1 promoter activity increased by ∼30% ( Figure 4C; n = 3, p < 0.05), while GFAP promoter activity decreased by ∼70% ( Figure 4F; n = 3, p < 0.001). On the other hand, SVZ-NPCs derived from Fxr2 KO mice showed no significant difference in either neuronal or astrocyte differentiation compared with WT cells (n = 3, p > 0.5). Next, we found that expressing exogenous FXR2 in Fxr2 KO DG-NPCs rescued the proliferation ( Figure 4G; n = 3, p < 0.05), neuronal differentiation ( Figure 4H; n = 3, p < 0.05), and astrocyte differentiation ( Figure 4I; n = 3, p < 0.05) deficits of Fxr2 KO DG-NPCs. Therefore, FXR2 regulation of DG-NPCs is likely intrinsic to the NPCs. Even though Fxr2 KO mice exhibit no obvious deficits during embryonic development ( Bontekoe et al., 2002), FXR2 deficiency may nonetheless have a developmental impact on adult NPCs.