This procedure was repeated 1,000 times to give an estimate of the null distribution (ρnull-modelρnull-model; see Figure S5B). The model correlation, ρmodelρmodel, was tested against the null distribution for significance (p = 0.05, Bonferroni corrected for M multiple comparison, where M is the number of significant spatial locations for each neuron). The model was considered to have significant predictive power for a neuron if there was at least one spatial location that was significant, according to the above criteria. We also

investigated two reduced versions of the pooling model (Figure S5C). The space-only version was obtained by averaging across orientation at each fine-grid location (Figure S5C, right upper panel). This model did not have any local orientation check details tuning. The orientation-only version was obtained by subtracting the average orientation response (as in the space-only model) from the measured data at each fine-grid location (Figure S5C, right lower panel). Thus, this model did not contain any local spatial information. The model correlations and null distributions for these reduced models were calculated using the same procedure described above for the full model. The explained variance of our model was estimated by first calculating the model correlation, ρmodelρmodel,

http://www.selleckchem.com/products/ABT-888.html as above, but on different jackknifed fractions of the data. Specifically, we calculated ρmodelρmodel between the predicted response map and the observed response maps from (1) the full data set, (2) 95% of trials (3) 90% of trials, (4) 85% of trials and (5) 80% of trials. We then performed a linear regression on the resulting ρmodelρmodel values against the reciprocal of the corresponding jackknife fraction values (1, 1/0.95, 1/0.9, 1/0.85, and 1/0.8). This procedure is designed to correct for the bias due to finite data set size (Brenner et al., 2000; Sahani and Linden, 2003; Machens et al., 2004). The square of the y-intercept of the regression

line was taken as the explainable variance for that RF location. The explained variances of the reduced space-only and orientation-only models GPX6 were calculated using the same procedure. This research was supported by grants from the NIH (R01 EY019493), the Alfred P. Sloan Foundation, the W.M. Keck Foundation, the Ray Thomas Edward career award in Biomedical Sciences, and the McKnight Scholar Award (to T.O.S.); NIH grant R01 EY013802 and the Gatsby Charitable Foundation (to J.H.R.); NIH grant R01 EY013802 and the Swartz Foundation (to J.F.M.); and by a Pioneer Fund postdoctoral fellowship (to A.S.N.). A.S.N. and J.F.M. designed the experiments, collected data, and developed the model and the statistical methods; A.S.N analyzed the data and ran the model simulations; A.S.N., J.F.M., J.H.R., and T.O.S. wrote the manuscript.

In close collaboration with a dear colleague of his, Jean-Pierre Tranzer at Roche in Basel, they

discovered through the use of electron microscopy that this drug selectively destroys sympathetic nerve endings. They suggested that 6-hydroxydopamine is taken up by these terminals where it readily oxidizes, with its killing specificity ultimately explained by the high local concentrations created by the dopamine transporter. Hans’s desire to further explore the mechanisms of action of 6-hydroxydopamine using LY294002 mw biochemical markers led him to join the laboratory of Julius Axelrod at the NIH. While of short duration, this stay had a profound impact on Hans. First, because of the discovery of transsynaptic induction (see below) and second because of the way science was done in the Axelrod laboratory. The lack of hierarchy, the openness for unexpected discoveries

that others would perhaps ABT-888 in vitro reject as a nuisance slowing the confirmation of preconceived ideas, the unusual career path of Axelrod, including his PhD late in life, all this was interpreted by Hans as indications that, after all, there might be room in Academia not only for adventure, but also for scientists with unconventional trajectories. Long after leaving the Axelrod laboratory, Hans would often talk fondly about “Julie,” as he would invariably say. As Hans

describes in his autobiography, the discovery of transsynaptic induction was an entirely unexpected consequence of the use of 6-hydroxydopamine. Together with Axelrod and Müller, Hans showed in a series of short but remarkable publications in 1969 that increased presynaptic activity leads to elevated levels of enzyme activity, until which they illustrated with tyrosine hydroxylase. While neither antibodies nor RNA probes were available at the time to directly quantify the levels of tyrosine hydroxylase, this work showed that increased enzyme activity necessitates ongoing transcription and translation, a conclusion that was at the time quite innovative with respect to how electric signals impact gene expression. Upon his return to Europe, Hans found it initially more difficult to publish in highly regarded journals and for years, when he would run out of patience with journal editors—and this would typically happen quite rapidly—he would often use the argument that, after all, he was just a boy from the Swiss Alps, unfamiliar with the sophisticated formulations that people learn by default (he thought) when brought up in large U.S. cities. Upon his return from the NIH, Hans spent a few years again in Basel, where he was appointed University Professor.

As a consequence, EAP amplitude is approximately proportional to the sum of the dendritic cross-sectional areas of all dendritic branches connected to the soma. Therefore, neurons with thick dendrites connected to the soma produce large EAPs and have the largest “radius of visibility” (Pettersen and Einevoll, 2008). At the same time, PSCs are mainly located along thin dendrites (i.e., much higher

axial resistance), preventing return currents from spreading along the whole neural morphology. Another important observation stemming from our simulations is the input specificity of the LFP composition. Although the LFP during the first 50–80 ms from UP onset is dominated by K currents originating from L5 pyramids for temporally coordinated input (Figure 7B), this switches to K currents from L4 pyramids for uncorrelated input SB431542 purchase (Figure 7A). Moreover, basket cells generally do not contribute markedly to the LFP, but this changes briefly 50 to 70 ms after UP onset. Thus, the LFP composition is not static but time- and state-dependent and is crucially impacted by the impinging input and the sort of

subthreshold and spiking activity it induces (especially proximally to the recording site). What are the functional (computational) ramifications of these observations? Coherence between spiking and specific LFP bands has been used to infer the relationship between synaptic input (hitherto considered to be reflected in the LFP) and neural output (spiking) and thereby specific mechanisms of information processing Dasatinib molecular weight within and across brain regions (Fries

et al., 1997, Lee et al., 2005, Montgomery et al., 2008, O’Keefe GBA3 and Recce, 1993, Rutishauser et al., 2010 and Womelsdorf et al., 2006). This raises the question of the extent to which the locally generated LFP (or particular bandwidths of it) represent actual synaptic input impinging on local neurons rather than spiking output (Buzsáki et al., 2012). For example, it was recently shown that spiking coherence to ripples during sharp waves in CA1 is partly attributed to spiking currents shaping the ripple signal (Belluscio et al., 2012 and Schomburg et al., 2012). Another question arises regarding how perturbing rhythmic LFP activity such as theta with tetanic stimulation at particular phases of theta induces potentiation or depression of synaptic strength (Hölscher et al., 1997, Hyman et al., 2003 and Pavlides et al., 1988). Other studies relate cognitive alteration to perturbation of neocortical UP-DOWN states (Marshall et al., 2006) or hippocampal sharp waves (Girardeau et al., 2009). Our population model does not attempt to reproduce any particular LFP rhythm, but it does link the LFP to biophysical processing. Thus, it can become a useful tool toward addressing the involvement of particular mechanisms during particular LFP bandwidths and phases and how perturbing them crucially alters other processing and, ultimately, cognitive function.

, 2011). Indeed, we have observed that MGE cells cultured in the presence of agonists of the Patched1-Smoothened (Ptch-Smo) pathway have longer primary cilia. Another major finding of our study is that the primary cilium of migrating MGE cells transduces Shh signal through a mechanism involving the Ptch-Smo signaling pathway. Shh is expressed in the migratory pathway of MGE cells (Komada et al., 2008 and this study). Smo see more immunostaining was observed in the primary cilium of MGE cells cultured in the presence of Shh or SAG, confirming a central role of the primary cilium in Shh signaling. Kif3a−/−

MGE cells, Ift88−/−, MGE cells, and cyclopamine treated MGE cells showed similar migratory defects that very likely resulted from impaired transduction of Shh signal in the primary cilium of migrating MGE cells. Although Shh functions as a chemo-attractant for tangentially migrating SVZ cells ( Angot et al., 2008) and as a chemoattractant or -repellent for growing axons ( Charron et al., 2003; Sánchez-Camacho and Bovolenta, 2009), neither clear attractive nor clear repulsive activity of Shh on MGE cells was observed in organotypic

slices. Rather, the primary cilium controlled the migration of MGE cells in a context dependent manner and facilitated MGE cell reorientation. Functional IFT prevented MGE cells to fasciculate on each other suggesting that signals transmitted through the primary LY294002 below cilium mediate repulsive interactions between migrating MGE cells and/or promotes adhesive interactions with other cells. It is established that future interneurons are maintained by CXCL12/CXCR4 mediated attractive interactions in their tangential cortical routes ( Stumm et al., 2003; López-Bendito et al., 2008; Lysko et al., 2011). From early developmental stages, however,

some neurons leave the tangential migratory streams to enter the CP ( Tanaka et al., 2003). Shh signal in the developing cortex promotes this process. Although interactions between migrating MGE cells and cortical axons are poorly documented in vivo ( Métin et al., 2000; Pinheiro et al., 2011), our results suggest that Shh signal could orient the migration of MGE cells toward the cortex along corticofugal axons or radial glia. Abnormal orientation of migrating MGE cells along these guiding structures might be responsible for the decreased number of Kif3a−/− cells that we observed in the supragranular layers of the parietal cortex. In conclusion, our study establishes that the CTR of long distance tangentially migrating GABA neurons regulates the migration of these neurons by gathering in a same area the GA through its cis-compartment, centrosomal MTs, and signaling pathways associated to the primary cilium.

These diseases potentially cause morbidity in cattle, leading to economic losses in tropical and subtropical countries. This tick species is responsible for annual losses of 2 billion dollars in Brazil ( Grisi et al., 2002). Traditional ALK inhibitor cancer control methods, using chemical acaricides such as organophosphates, formamidines, pyrethroids and phenylpyrazoles, have been only partially successful due to resistance problems (Castro-Janer et al., 2010), use of chemicals lead to residues in animal products (meat and milk) and environmental pollution. However, alternative acaricides and strategies have been investigated, including secondary metabolites found in plants

as potential sources for arthropod control products (Isman, 2006). Recently, we demonstrated the acaricidal activity of Calea serrata Less. (Asteraceae) ( Ribeiro et al., 2008 and Ribeiro et al., 2011). This plant species, known in Southern Brazil as “grass snake”, “bitter tea” or “breaks everything”, is used in Afro-Brazilian religious rituals and in folk medicine to treat ulcers and liver diseases ( Simões et al., 1990 and Vendruscolo and Mentz, 2006). The n-hexane extract of C. serrata demonstrated activity against larvae of R. microplus and Rhipicephalus sanguineus ( Ribeiro et al., 2008). However, it is important to understand the mechanism of the acaricidal action of this extract. Previous phytochemical studies carried

out by Steinbeck et al. (1997) revealed the presence of chromenes (eupatoriocromene and precocene II) in the n-hexane extract of this plant. Several chromenes are known to have insecticidal and acaricidal actions ( Addor, 1994). Precocene II can Wnt inhibitor affect the endocrine system of insects, acting as antagonists of juvenile hormone ( Bowers et al., 1976 and Pamo et al., 2004). The endocrine regulation of the life cycle of insects is based on ecdysteroids (ecdysone and 20-hydroxyecdysone), juvenile hormone, and a myriad of neurosecretory peptide hormones. The ecdysteroids have an important role in endocrine

Sitaxentan regulation of development and reproduction in ticks ( Rees, 2004 and Seixas et al., 2010), although the occurrence of juvenile hormone or juvenile hormone-like molecules nowadays is not clear in tick species ( Neese et al., 2000). Esterases, a group of multifunctional enzymes, are related to several physiological activities, such as regulation of juvenile hormone levels, digestive processes, reproductive behavior and nervous system functions (Galego et al., 2006). Carbamate and organophosphate compounds have the same mechanism of action, based on the inhibition of acetylcholinesterase (AChE) in the nervous system. Their inhibitory action on insect AChE function prolongs the neural excitation caused by the neurotransmitter acetylcholine leading to neuromuscular paralysis (Lees and Bowman, 2007) and death (Tan et al., 2011). AChE activity has been demonstrated in homogenates from R. microplus larvae ( Roulston et al., 1966). Baffi et al.

Those who responded “no” and “not sure” were deemed not recovered. This question has been shown to correlate well with WDQ scores.4 No data was gathered on

treatment during the last three months. Also at 3 months post-injury, the BPPT was performed while the examiner was blind to the results of the other data. The BPPT was performed as described elsewhere.2 In brief, the BPPT was always performed on the left side first, the technique involving the application of gentle shoulder girdle depression, glenohumeral abduction and external rotation in the coronal plane, with wrist and finger extension and CP-673451 research buy elbow extension. The range of elbow extension was measured at the subjects’ pain threshold using a standard goniometer aligned along the mid-humeral GSK1120212 in vivo shaft, medial epicondyle and ulnar styloid. If the subject did not experience pain, the test was continued until the end of available range. At the completion of this test, the subjects were asked to record their pain on a 10-cm visual analogue scale (VAS). All subjects were, at the time of the study, in a system of new legislation that places a cap on compensation for whiplash grade 1 and 2, of $4000 CAN, with a standardized diagnostic treatment protocol applied to each subject. This system has been described elsewhere.17 All subjects had

filed a claim with an insurance company to receive treatment benefits. Crude associations between age, gender, initial WDQ, and BPPT angle and VAS score were assessed using χ2 tests, with α levels set at 0.05. For age, the clinically meaningful categories were age ≤ 40 and age > 40. As the distribution of age and WDQ scores may not be normal, these continuous variables were also converted to categorical variables. For age, the clinically meaningful categories (shown to have prognostic significance) were age ≤ 40 and age > 40. For WDQ, the clinically meaningful categories were scores in the low (0–40), medium (41–80) and high (81–130) range. After examining for confounding and interactions, the remaining terms were included in a final logistic

regression. Spearman’s rank correlation coefficient was calculated for recovery and both BPPT angle and VAS score. Significance was set at p < 0.05. All analyses were completed using STATA/SE, version 10.0 for because Macintosh (STATA CORP, College Station, TX, USA). The 69 subjects were 32 males, 37 females, mean age 37.5 ± 13.0 years (range 18–71, mean ± SD). At the 3-month follow-up, recovery was reported by 35 of 69 subjects. Age, gender, and initial WDQ score did not correlate recovery or BPPT results, and therefore the group was analysed as a whole. At the 3-month follow-up, the BPPT elbow extension (from 180°) was 41.5 ± 23.0° (mean ± SD), and the VAS score for the BPPT was 2.2 ± 1.2 (out of 10, mean ± SD). As there were no side-to-side differences, the results of both sides were averaged.

In these pathways, the internalized structure is a small, membrane-bounded vesicle and contains only small amounts of extracellular fluid. Membrane receptors, on the other hand, become clustered and enriched in the invaginating EGFR targets vesicle. Other internalization pathways, such as macropinocytosis and phagocytosis, involve large regions of the plasma membrane (Flannagan et al., 2011 and Kerr and Teasdale, 2009). Macropinocytosis in neurons has been described in multiple contexts (Bonanomi et al., 2008, Kabayama et al., 2011 and Shao et al., 2002), but the extent of phagocytosis carried out by neuronal cell types

is not well established, and might be very restricted (Bowen et al., 2007 and Lu et al., 2011). The presence of several independent endocytic pathways allows preferential internalization of some receptors and exclusion of others. Entry via distinct pathways can also change the trafficking fate of the receptor and extent and lifetime of signaling. In principle, endocytosis can regulate receptor

surface expression in a spatially and temporally precise fashion. After endocytosis, cargo molecules are transported through a complex endosomal system that sorts them to be degraded, stored, or recycled back to the plasma membrane (Figure 1). Transport to the trans-Golgi-network (TGN), or even back to the Golgi and endoplasmic reticulum, can also occur under some circumstances. At its simplest, proteins can be endocytosed Dasatinib cost and removed from their current location and then transported to the lysosome for degradation. Alternatively, endocytosed proteins can be recycled back to the plasma membrane (reviewed in Huotari and Helenius, 2011). Even though the biosynthetic pathway and endocytic pathway are conceptualized as separate entities, it is clear that the two systems are interconnected (Schmidt and Haucke, 2007). There is retrograde transport from endosomes back to the TGN, and there is also transport of newly made, biosynthetic cargo from the TGN to various Bay 11-7085 endosomes before delivery to the plasma membrane (Ang et al., 2004 and Fölsch et al.,

2009). Several distinct types of endosomal compartments have been identified (Figure 1): early endosomes (EEs), recycling endosomes (REs), late endosomes (LEs), and lysosomes (lys) (Mukherjee et al., 1997). This simple classification, however, does not do justice to the complexities of the endosome, even in nonpolarized cells. The main endosomal compartments can be distinguished either by functional criteria or by colocalization with markers. Because several proteins are highly enriched in some of these compartments, proteins are frequently used as markers: rab4 and rab5 for EE, rab11 for RE, and rab7 for LE (Zerial and McBride, 2001). Caution is necessary, though. Commonly used markers are usually in more than one compartment, since the compartments are continuously formed and consumed with constant flux among them (Huotari and Helenius, 2011).

Application of GABAAR and GABABR blockers to PSEM-treated slices produced only an ∼12% further increase in the SC-evoked PSP (to 9.77 ± 1.01 mV, p < 0.01, n = 6; Figure 6E1). Thus, CCK IN silencing blocks almost all SC-evoked FFI. Furthermore,

we found that CCK INs also make a dominant contribution to the FFI in CA1 PNs evoked by PP stimulation (Figure S4). Selective silencing of PSAM+ CCK INs with PSEM application produced an 80% reduction in the amplitude of the PP-evoked somatic IPSC (p < 0.0005, n = 5) and a corresponding increase Autophagy inhibitor in the PP-evoked PSP (p < 0.0001, two-way ANOVA with Sidak’s multiple comparison test, n = 5). These silencing experiments demonstrate that the CCK INs are responsible for the majority of FFI that controls synaptic responses of CA1 PNs elicited by both the SC and PP inputs. The findings that CCK IN silencing robustly increased the PSP amplitude (by ∼100%) and occluded any further increase in the PSP upon subsequent GABAR blockade resemble the effects seen upon induction of ITDP (Figure 2). Such results support the view that selective silencing of CCK INs produces a large reduction in inhibition capable of accounting for the magnitude

of iLTD observed during ITDP. To determine whether the CCK INs are indeed required for expression of Gefitinib datasheet iLTD during ITDP, we examined the effects of PSEM-mediated silencing on the magnitude of ITDP. PSEM ligand was applied (at 3 μM) to hippocampal slices either from CCK-ires-Cre mice injected with rAAV that expressed PSAM in a Cre-dependent manner (CCK-Cre-PSAM) or from uninjected control littermates (CCK-Cre). When the control slices were exposed to PSEM, the pairing protocol elicited a normal-sized ITDP (2.9-fold ± 0.26-fold) ( Figures 1C and 2A1–2A4). In contrast, there was a strong suppression of ITDP when the pairing protocol was applied to PSAM-expressing slices exposed to PSEM (p < 0.0002, unpaired t test; CCK-Cre PSAM group, n = 7; CCK-Cre group, n = 6). With CCK INs silenced, the pairing protocol produced only a 1.42-fold ± Oxymatrine 0.09-fold

increase in the SC-evoked PSP, similar to the magnitude of ITDP during GABAR blockade ( Figure 1C). Silencing of CCK INs also significantly reduced the extent of iLTD of the IPSC during ITDP. Thus, PSAM-expressing slices exposed to PSEM displayed only an 8.3% ± 1.7% decrease in the SC-evoked IPSC following induction of ITDP compared to the 60.5% ± 3.2% decrease in the IPSC seen with control slices (p < 0.0001; Figures 7B1–7B3). Application of GABAR antagonists 30–40 min after ITDP induction caused only a small increase (∼15%) in the SC PSP in both groups (p = 0.7273, one-way ANOVA; Figure 7A3), indicating a similar extent of loss of inhibition. These findings support the hypothesis that iLTD during ITDP results from a selective depression of FFI mediated by CCK INs.

To quantify the changes PF-06463922 in vitro in mitral cell responses, we calculated the change index (CI) for each responsive mitral cell-odor pair on each trial (trial X) of a given day as (response on trial

X – the initial response on day 1)/(response on trial X + the initial response on day 1). Thus, CI ranges from −1 to 1, where a value of −1 represents a complete loss of response, 1 represents emergence of a new response, and 0 represents no change. On the first day of testing (day 1), the average CI values for both odor sets A and B steadily declined during repeated odor exposure (Figure 4D). During days 2–6, the CI value for set A odors progressively decreased with little recovery from previous days and reached a steady-state value after 4–5 days of daily experience. When

responses to both odor sets were tested on day 7, the SB431542 concentration average CI value for the less-experienced odors (set B) was significantly greater than that of the experienced odor set (Figure 4D, p < 0.001). Mitral cell-odor pairs whose response onset times are during odor stimulation (“on” responses) and after odor stimulation (“off” responses) showed similar experience-dependent plasticity on day 7, with a trend for “on” responses to be more strongly affected (CIs for the experienced odor set are the following: “on” response: −0.585 ± 0.016; “off” response: −0.383 ± 0.019. CIs for the less-experienced odor set are the following: “on” response: −0.272 ± 0.022; “off” response: −0.158 ± 0.023). Changes in raw dF/F values or fractions of responsive cells also support odor specificity of the plasticity (Figure S4). We did not detect significant changes in respiration rates throughout the course of the experiment (respiration rates during all

odor trials were the following: on day 1: 3.39 ± 0.20 Hz versus on day 7: 3.44 ± 0.19 Hz, p = 0.900; on day 7, experienced odor trials: 3.36 ± 0.21 Hz versus less-experienced odor trials: 3.47 ± 0.19 Hz, p = 0.757). In addition, CI did not correlate with differences in the levels of GCaMP3 expression across cells (Figure S4). The slight deviation from zero in CI for set B odors at the beginning of testing on day 7 is not related over to the number of set A odors each cell responds to (Figure S4) and is similar to what was observed in a separate set of animals, which only experienced odors on day 1 and day 7 (Figure S5). This suggests that the small change in CI for set B odors on day 7 is not due to nonspecific effects of set A odors, but rather reflects the fact that experience with set B odors on day 1 causes a weak but long-lasting reduction in responsiveness. Together, these results indicate that the weakening of mitral cell odor representations occurs within each day, accumulates over days of experience, and is specific to experienced odors.

The input-output curves showed that the fEPSP slope of the EC-DG pathway was decreased in the EC::TeTxLC-tau-lacZ mice relative to control littermates by ∼35% at postnatal day 11 (P11) (Figures 1D and 1E), while the fiber volley amplitude, which represents the number of axons, was similar between them (Figure 1D and data not shown). This indicates that synaptic transmission

by tTA-expressing neurons in the EC::TeTxLC-tau-lacZ line is effectively inactivated by TeTxLC. We then used these mice to examine the developmental projection http://www.selleckchem.com/products/MK-2206.html of active and inactive EC axons in the EC transgenic lines. Both active (EC::tau-lacZ) and inactive (EC::TeTxLC-tau-lacZ) EC axons reached the DG between P6 and P9, as visualized by lacZ staining, without any aberrant projections (Figure 1F). This result suggests Talazoparib cell line that initial axon projections from the EC to the DG are largely independent of synaptic neurotransmitter release. In contrast, inactivation of EC axons resulted in their elimination from the DG after they developed.

Active EC axons (EC::tau-lacZ) increased in the DG from P12 to P16 (Figures 1F and 1G). However, inactive axons (EC::TeTxLC-tau-lacZ) were quickly eliminated from the DG after P12, and very few remained by P18 (Figures 1F and 1G). This axon elimination was likely initiated by axon retraction (also see Figure 4), because (1) no apparent cell death was detected in the EC at P18 (Figure S1B available online), and (2) EC axons were still detected in the presubiculum at P21 (Figure S1C). These results

suggest that EC axons are refined after P12 in an activity-dependent manner. In EC::tau-lacZ mice, lacZ intensity decreased between P16 and P21 by ∼25% (Figure 1G), suggesting that EC axons are refined during normal development and that the elimination of inactive axons in EC::TeTxLC-tau-lacZ mice reflects an exaggerated instance of normal physiological refinement. Since only 43% of the superficial layer neurons of the medial EC express TeTxLC in EC::TeTxLC-tau-lacZ mice (Yasuda and Mayford, 2006), there are two possible mechanisms for the elimination of inactive axons: (1) inactivity per se drives Non-specific serine/threonine protein kinase axon elimination, or (2) they are eliminated via activity-dependent competition with other active EC neurons. To distinguish between these possibilities, we globally suppressed neural activity of EC axons by injecting the sodium channel blocker tetrodotoxin (TTX) (Burrone et al., 2002 and Echegoyen et al., 2007) into the DG of EC::TeTxLC-tau-lacZ mice once a day from P9 and analyzed the elimination of TeTxLC-expressing EC axons at P12, P14, and P16 (4, 6, or 8 days total of TTX injections) (Figure 2A). TTX injections markedly suppressed the elimination of TeTxLC-expressing EC axons between P12 and P16 (Figures 2B and 2C). Therefore, the refinement of EC axons in the DG is mostly achieved by an activity-dependent competition between EC neurons.