, 1995). Studies of the anatomy of this region found that it contains extensive basement membrane and extracellular matrix (ECM) components, including laminin Epacadostat ic50 and heparan sulfate proteoglycans (HSPGs). These matrix components appear to contact all the cell types in the adult VZ-SVZ (Mercier et al., 2002 and Shen et al., 2008). The high degree of basement membrane organization in

the adult VZ-SVZ is absent in other areas of the brain. HSPGs can directly control local availability of growth factors such as fibroblast growth factor (FGF), and have since been suggested to affect proliferative signaling and progenitor activity (Kerever et al., 2007). The extensive vasculature underlying the adult VZ-SVZ also provides a route for interactions between endothelial cells, blood-borne factors, and neural progenitors. Type B1 cells, in addition to their apical contacts with the CSF, extend a long process terminating in an endfoot that directly contacts blood

vessels (Figure 1; Mirzadeh et al., 2008 and Tavazoie et al., 2008). Type C cells, and in particular clusters of proliferating C cells, are also closely associated with blood vessels, suggesting that the perivascular environment contains signals that allow transit-amplifying cell generation or proliferation (Shen et al., 2008 and Tavazoie et al., 2008). Studies using injected tracer molecules indicate that the vasculature in this region is more “leaky” or permissive than the blood-brain barrier in other regions, possibly allowing signals from the bloodstream to diffuse into this region and impact the niche (Tavazoie et al., 2008). Endothelial cells themselves GSK1349572 may secrete factors that contribute

to stem cell self-renewal or proliferation, and coculture of endothelial cells has been reported to enhance in vitro neurosphere generation from embryonic progenitors (Shen et al., 2004). Blood vessels have also been shown to serve as a scaffold for neuroblast migration, potentially through the release of neurotrophic factors (Snapyan et al., 2009 and Whitman et al., 2009). Recent studies have identified however SDF-1/CXCR4-mediated signaling as one pathway by which endothelial cells appear to promote progenitor activation, alter the binding of progenitor cells to laminin in the ECM, and affect neuroblast migration in the adult VZ-SVZ (Kokovay et al., 2010). Vascular endothelial growth factor (VEGF) signaling has been implicated in NSC and progenitor survival, proliferation within the VZ-SVZ, and neuroblast migration and maturation, highlighting a pathway that may be able to act on both VZ-SVZ progenitors and the vasculature in this region (Zhang et al., 2003, Schänzer et al., 2004, Gotts and Chesselet, 2005c, Meng et al., 2006, Wada et al., 2006, Mani et al., 2010, Wittko et al., 2009 and Licht et al., 2010). Angiogenesis elsewhere in the brain, after tumor growth or injury, has also been reported to induce proliferation and migration of neural progenitors (Schmidt et al., 2009 and Harms et al.

, 2009), a bHLH transcription factor required for survival of GABAergic progenitors in different regions of the central nervous system (CNS), including the diencephalon ( Bradley et al., 2006; van Eekelen et al., 2003). Tracing of Tal1-expressing neurons in the r-Th indicates that this progenitor pool will form the IGL and, to a minor extent, part of the ventral lateral geniculate (vLGN) ( Jeong et al., 2011). Much less selleck chemicals llc information is available regarding the embryonic origin of other nuclei of the SVS, but GABAergic transcription factors

that, like Tal1, are expressed in the r-Th have also been described in the posterior pretectum, notably Helt (alias Mgn) and Sox14. Helt encodes a bHLH-Orange transcription factor with an essential role in differentiation of GABAergic neurons in the midbrain ( Guimera et al., 2006a, 2006b; Nakatani et al., 2004). Sox14 is a member of the SRY-related HMG box class of transcription factors and it is thought to act as a transcriptional repressor to control lineage fate decisions ( Hargrave et al., 2000; Hashimoto-Torii et al., 2003; Uchikawa et al., 1999). In this Article, we identify Sox14 as a marker for SAHA HDAC all nuclei of the SVS and show that its expression is required to drive development of a functional network supporting light-entrained circadian behaviors.

We provide evidence on the common developmental origins of the SVS from two related neuronal progenitor domains, one in the r-Th and the other in the pretectum. Furthermore, we describe how sequential waves of tangential migration convert the simple organization of the two progenitor territories into the complex architecture of the SVS. This research redefines the role of the SVS as an important regulator of circadian behaviors. Expression of proneural bHLH transcription

factors in the diencephalon defines territories with a determined neurotransmitter fate. Expression of Neurog2 in the rostral pretectum, caudal thalamus, and zona limitans intrathalamica (ZLI) defines diencephalic regions with an excitatory fate ( Figures 1A and 1B). By contrast, expression of the bHLH transcription factor Ascl1 defines the caudal pretectum, rostral thalamus, whatever and prethalamus as having an inhibitory fate ( Figures 1A and 1B). Upon exiting the cell cycle, neuronal progenitors upregulate expression of transcription factors that are predictive of their nuclear identity. Lhx9-positive neurons contribute to all thalamic nuclei projecting to the cortex ( Figures 1A and 1B). Dlx2-positive neurons form prethalamic nuclei including the reticular nucleus of the thalamus and the ventral part of the LGN complex (vLGN) ( Figures 1A and 1B). We describe a neuronal population in the r-Th and caudal pretectum defined by the hierarchical expression of three transcription factors.

, 2009), these lines do not fully recapitulate endogenous expression and show ectopic Cre recombination. We generated both Dlx1-CreER and Dlx5-CreER knockin drivers, which permit Dlx1+ and Dlx5+ interneurons to be identified and manipulated throughout development. As Dlx1 and Dlx5 are expressed predominantly in the SVZ in putative committed precursors at mid-gestation (i.e., becoming postmitotic after a limited number buy BIBW2992 of cell division) ( Eisenstat et al., 1999), CreER induction around this time (e.g., at E12) likely labels cohorts of GABA neurons with similar birth dates. Our initial characterization with E12 induction suggests that Dlx1 and Dlx5 may be expressed

in at least partially nonoverlapping

populations of progenitors. During tangential migration at E13, both the E12-induced Dlx1 and Dlx5 cohorts appeared to take similar routes, via the subventricular zone, into the cortex ( Figures 3A and 3B). By E15, however, the two cohorts showed very different patterns of migration. Whereas the Dlx1 cohort migrated throughout the marginal zone (MZ), cortical plate (CP), and intermediate zone (IZ), the Dlx5 cohort migrated predominantly in MZ ( Figure 3C-F). In mature cortex (P21), both cohorts settled in deep cortical layers despite their different migration routes, with a larger fraction of Dlx5-CreER-labeled neurons situated deeper in layer 6 than Dlx1-CreER-labeled neurons ( Figures 3G–3I). At later embryonic stages (e.g., E15), induction in Dlx1- and Dlx5- drivers gave rise to a very different pattern in the mature cortex buy C59 wnt (P21, Figures 3J and 3K). The Dlx1 driver mainly labeled upper layer interneurons. Many of these interneurons showed bipolar morphology and were reminiscent of CGE-derived populations such as VIP or CR positive interneurons. On the other hand, the Dlx5 driver labeled broader populations in all layers, suggesting that induction occurred not only in SVZ GBA3 progenitors but

also in migrating cells that had earlier become postmitotic. This distinction between the Dlx1- and Dlx5- drivers became more evident with adult induction ( Figures 3L and 3M), indicating that in the mature cortex Dlx1 expression is increasingly restricted to a small subset of interneurons, whereas Dlx5 expression is increasingly more ubiquitous among GABAergic neurons. Together, our initial characterization of these two driver lines demonstrated that Dlx1 and Dlx5 are differentially expressed in progenitors and developing interneurons at different developmental stages and thus may play different roles in GABAergic circuit development and function. In mammals, GABA is synthesized by two isoforms of glutamic acid decarboxylases GAD67 and GAD65, encoded by the Gad1 and Gad2 genes, respectively, and coexpressed in most brain regions ( Soghomonian and Martin, 1998).

There was a wide variation across countries with proportions of young people meeting the PA guidelines ranging from 26% in Belgium (Flemish) to 57% in Ireland for boys and 12% in France to 44% in USA for girls. In all countries and across all age groups, more boys (mean 40%) than girls (mean 27%) met the UKHEA PA guidelines although the gender differences were small in some countries. A strong trend of HPA decreasing with age was noted.21 Data from 16,410 U.S. adolescents from the 2009 Youth Risk click here and Behaviour Surveillance Survey (YRBSS) indicated that 37% of 15–18-year-olds experienced PA that increased their HR and made them breathe

hard some of the time for a total of at least 60 min per day, on at least 5 days per week. More boys than girls (46% vs. 28%)

met the PA guideline. 34 A survey of 32,005 13–18-year-olds from Hong Kong, China reported 64% of Chinese boys and 40% of Chinese girls to achieve 60 min of moderate intensity PA after school on 5 days per week. Similar to studies of western youth a declining trend of HPA with age was observed.35 A study of 2101 6–18-year-old Russians used the ICC PA guidelines and reported that although nearly 70% of Russian youth met the SB203580 purchase guideline for daily PA fewer than 45% met the guideline advocating sustained periods of MVPA. A marked decrease with age in the percentage of young people who experienced sustained periods of MVPA was noted with none of 17–18-year-olds meeting this PA guideline.36 Although the use of different methodology means that comparisons must be carried out cautiously, nearly a recent WHO sponsored survey of 72,000 youth, aged 13–15 years, from 34 developing countries suggests that self-reported levels of HPA from developing countries are lower than those from Europe, China and North America. Only 24% of boys and 15% of girls were reported to experience 60 min of daily MVPA.23 Studies using pedometers provide limited insights into the percentage of young people meeting PA guidelines but

they are consistent in reporting boys to be more active than girls at all ages from 7 to 18 years with HPA declining in both genders with age.3 One study of Canadian youth used a cut-off point of 15,000 steps per day as a guideline and reported 6%–17% of girls and 14%–33% of boys to meet this target.37 The percentage of young people reported to be physically active in studies using accelerometers varies from 0 to 100% depending on the activity cpm defining the required intensity of PA.7 For example, 2185 9- and 15-year-olds were recruited from four European countries and monitored for 3 or 4 days including, where possible, both weekend days. Using total activity counts boys were more active than girls at both ages and the 9-year-olds were more active than the 15-year-olds. The authors estimated that at 9 years >97% of children and at 15 years 82% of boys and 62% of girls experienced 60 min of moderate PA per day.

R18 increased the percentage of cohorts with randomization of AP guidance along the longitudinal axis (p = 0.0041), but there was no significant effect on the amount of stalling or recrossing axons (Figure 6B). When we quantified the degree of AP randomization by measuring the fraction of

anterior fluorescence, there was a significant decrease in the amount of anterior axons in the presence of R18 (Figure 6C). The decrease was in between that observed for the Wnt1-Cre;Smon/c and Math1-Cre;Smon/c mice. To inhibit 14-3-3 activity specifically in neurons, we turned to the developing chick embryo. Plasmids encoding R18 or a control WLRL peptide fused to EGFP MS-275 research buy (Kent et al., 2010) were injected into chick neural tubes and electroporated unilaterally. Two days later, the embryos were dissected and the commissural axon trajectories analyzed in the open-book format. Electroporated neurons were

identified by EGFP expression. In neurons expressing control WLRL-EGFP, the vast majority (92%) of axons correctly made an anterior turn after crossing the floorplate, with very few axons making a posterior turn. In contrast, neurons expressing R18-EGFP had a different distribution of phenotypes, with significantly fewer axons (58%) making the correct anterior turn (p < 0.001) and significantly more axons (35%) turning posteriorly (p < 0.001) (Figure 6D). Notably, as with the Tat-R18-YFP-treated rat open-book cultures (Figures

6A and 6B), there was no significant difference in the percentage of CHIR-99021 molecular weight axons stalled in the floorplate or after floorplate exit, indicating that 14-3-3 activity is required Dichloromethane dehalogenase for AP guidance, but not floorplate crossing and exit. This is different than what we observed in the Wnt1-Cre;Smon/c and Math1-Cre;Smon/c mice, which have defects in both AP guidance and floorplate crossing and exit. Together with our in vitro data demonstrating that 14-3-3 activity is required for the switch in Shh response from attraction to repulsion, this implicates 14-3-3 proteins in mediating the repulsive response to Shh in postcrossing commissural axons. If 14-3-3 proteins are key mediators of the switch in the polarity of the turning response, overexpression of 14-3-3 proteins should be sufficient to prematurely activate the switching program in young neurons. We tested this in vitro by transducing dissociated commissural neurons with HSV (herpes simplex virus) expressing either 14-3-3β or 14-3-3γ, the two 14-3-3 isoforms that are enriched in postcrossing commissural axons. Control neurons transduced with GFP alone were attracted up a Shh gradient at 2 DIV (mean angle turned of 18.0° ± 5.1°) (Figures 7A and 7B). Expression of either 14-3-3β or 14-3-γ significantly changed the turning response of the neurons to a Shh gradient. Overexpression of 14-3-3β silenced the attractive response to Shh (mean angle turned of −2.4° ± 4.2°).

Given the potential of human pluripotent stem cells and their differentiated cell types to model keys aspects of neurological disease, an obvious extension of this platform is in its use for drug discovery and predictive toxicology. As iPS cells can be generated from different patient populations, a diversity of drug responses and toxicity profiles could potentially be captured. High rates of attrition of new drugs are mostly attributed

to failures in clinical efficacy or unforeseen toxicities and safety concerns, often occurring in later stages of clinical trials. Nearly 90% of new drugs tested in humans fail to ultimately come to clinical approval, with central nervous system disorders as a therapeutic area, among those with the highest rate of attrition (Kola and Landis, 2004). Arguably, these failures Cabozantinib purchase have resulted from a reliance on imperfect models used during preclinical development. One could envision using human pluripotent cell-based assays in lead optimization for efficacy and also to identify, prior to first-in-human studies, drug toxicities. As disease-specific stem cell models for neurological diseases continue to be validated, they are poised

to become unprecedented tools for drug discovery using human cells (Ebert and Svendsen, 2010 and Rubin, 2008). However, before their full potential can be realized, several challenges must be overcome. IWR-1 purchase It will be critical to identify robust assays that display disease-relevant phenotypes and are readily amenable to large-scale drug screening. For example, high-throughput screening of compounds that improve motor neuron survival in SMA and ALS is one such achievable goal (Di Giorgio

et al., 2008, Ebert et al., 2009 and Rubin, 2008). Thus, optimizing stem cell cultures and differentiation protocols for large-scale, automated, multiwell formats will be important technical goals. Pluripotent stem cells may also find an important function in predicting whether lead compounds identified using the cells of a single patient will be equally effective in a large cohort of individuals. To this end, one could imagine convening a large set of iPS cell lines, which could then be arrayed in not multiwell format. These “arrayed” stem cells would then be differentiated in parallel within the multiwell format into neurons that then could be exposed to the novel lead molecule. If the newly identified lead compounds worked well in disease models made from each of the genetically diverse cell lines within the array, then it could provide additional confidence that the compound in hand would function in a large number of patients. In turn if compounds are found to function in the neurons of some but not all stem cells within the array, the genetic signature of cells that respond best can be identified. This information would then be used to convene a clinical trial and administer the compound only to individuals with the response genotype.

3% ± 8.2%, n = 9; DR in stressed: −11.0% ± 8.3%, n = 9, p < 0.001). To test the specificity of this stress-induced memory deficit, we also subjected animals to the object location task, a paradigm for the PFC-independent memory (Barker et al., 2007). As shown in Figure 1D, both control groups and stressed animals (restraint, 7 day) showed similar discrimination between the object that had changed position than the object that had remained in a constant position (DR in control: 58.1% ± 5.4%, n = 6; DR in stressed: 47.7% ± 15.7%, n = 6, p > 0.05). In contrast to the impaired temporal order recognition memory, rats exposed to

repeated restraint stress showed no changes in anxiety-related behavior or selleck inhibitor locomotive activity (Figure 1E), as indicated by the amount of time spent in the open-field center (control: 7.3 s ± 0.9 s; stressed: 7.3 s ± 1.5 s, n = 8 pairs, p > 0.05) and the number of midline crossing in a cage (control: 10.2 ± 1.2, stressed: 11.5 ± 1.8, n = 6 pairs, p > 0.05). To find out the onset of the detrimental effects of stress on cognition, we exposed young male rats to various days (1,

3, 5 and 7) of restraint stress. PI3K Inhibitor Library cell line As shown in Figure 1F, TOR memory was largely unchanged by 1 or 3 day stress but was significantly impaired in animals exposed to 5 or 7 day stress (p < 0.001, n = 6 pairs per group). After 3 day withdrawal from the repeated stress, TOR memory still showed deficiency (p < 0.01, n = 6 pairs) but recovered after 5 day withdrawal (n = 6 pairs). To test whether glutamatergic transmission in PFC is critical for the object recognition memory, we gave animals a stereotaxic injection of the NMDAR antagonist APV and AMPAR antagonist CNQX to PFC prelimbic regions bilaterally. As shown in Figure 1G, APV+CNQX-injected animals lost the normal preference to the novel (less

recent) object (DR in saline: 36.8% ± 10.3%, n = 7; DR in APV+CNQX: −20.4% ± 8.7%, n = 11, p < 0.001), similar to the animals exposed to repeated stress. The total exploration time in the two sample phases and the subsequent test trial was unchanged by any of these treatments (Figure S1 available online). Taken together, it Cytidine deaminase suggests that repeated stress has a detrimental effect on recognition memory, which may be due to the loss of glutamatergic transmission in PFC. To find out the impact of repeated stress on glutamatergic transmission, we examined the input/output curves of AMPAR- and NMDAR-mediated synaptic currents (EPSC) in PFC pyramidal neurons from stressed, young (4-week-old) male rats. As shown in Figures 2A and 2B, AMPAR-EPSC and NMDAR-EPSC induced by a series of stimulus intensities were markedly reduced in neurons from animals exposed to repeated (7 day) restraint stress or unpredictable stress (AMPA: 40%–60% decrease, p < 0.01, ANOVA, n = 16–29 per group; NMDA: 38%–57% decrease, p < 0.

Extinction did not change the expression of PV in the SCR7 mouse soma of BA interneurons (Figures 4A and 4B). Next, we analyzed the presence of PV around the soma of BA fear neurons. We verified that our perisomatic PV immunolabeling represented perisomatic synapses (Figure S3A). Consistent with the extinction-induced increase in perisomatic GAD67, extinction also increased perisomatic PV around the silent fear neurons (Figure 4C). Again, there was no significant increase around the active fear neurons (Figure 4D). The effects of extinction on perisomatic PV seemed to reflect changes in synapse numbers (Figures S3B and S3C). Importantly, the increase in perisomatic PV that we detected with image analysis is similar to that reported

to increase perisomatic inhibition using electrophysiological analysis (Gittis et al., 2011 and Kohara et al., 2007). Thus, our data suggest an extinction-induced increase in perisomatic inhibition underlies the decreased number of active BA fear neurons and the resulting silencing of the fear memory circuit. This reveals a direct connection between extinction-induced structural and functional changes in the BA. We asked whether the extinction-induced increase in perisomatic PV might have reversed any fear conditioning-induced changes in those synapses, which would indicate that BA perisomatic inhibitory synapses were part

of the original fear circuit. To address this GSK1120212 question, we performed a separate experiment in which we compared a fear conditioned group (FC) with

a home cage group (HC) (Figures 5A and 5B). Consistent with our previous study (Reijmers et al., 2007), BA neurons activated during fear conditioning were tagged with long-lasting expression of GFP (Figure 5C). During retrieval on day 4, the FC group showed significant freezing (Figure 5D). The retrieval of contextual fear caused activation of both nontagged (GFP−Zif+; Figure 5E) and tagged (GFP+Zif+; Figure 5F) neurons in the BA, with a preferential reactivation of the tagged BA fear neurons (Figures 5E and 5F). 17-DMAG (Alvespimycin) HCl Importantly, we did not find fear conditioning-induced changes in perisomatic PV around silent or active fear neurons (Figures 5G and 5H). These data strongly suggest that the extinction-induced changes in PV+ perisomatic synapses constituted a new form of learning that occurred within the extinction circuit. In addition to PV+ perisomatic synapses, the BA also contains perisomatic inhibitory synapses that originate from cholecystokinin (CCK) interneurons (Yoshida et al., 2011). We therefore examined whether fear extinction also affected perisomatic CCK+ synapses. Extinction did not change the expression of CCK in the soma of BA interneurons (Figures 6A and 6B). In addition, perisomatic CCK around fear neurons, either silent or active, was not altered by fear extinction (Figures 6C, 6D, S4A, and S4B). Fear conditioning itself also did not change perisomatic CCK in the BA (Figures S4C and S4D).

The depth of its impact in the consciousness of medical researchers may be seen by the fact that in reviews for two disparate conditions (phantom limb pain54 and stress incontinence in women55), the authors specifically comment on the absence of Tai Ji Quan studies

related to these conditions. However, BKM120 it is more clearly evident in the increasing number of studies using Tai Ji Quan to address a growing array of conditions ranging from age-related decline in physical function to psychological well-being and metabolic pathologies. Unfortunately, very little of the work done to date is part of a deliberate and well-planned strategy to systematically address efficacy, effectiveness and cost-effectiveness issues related to Tai Ji Quan as an intervention to prevent health declines or to enhance physical and psychological function. Despite the high quality of some individual research projects, methodological weaknesses in Tai Ji Quan efficacy

studies and the overall disjointed and inconsistent research approach to examining Tai Ji Quan does not provide sufficient grounds for governmental or non-governmental organizations to underwrite comprehensive implementation of Tai Ji Quan for the good of the public’s health.10 and 53 Concerted, systematic and coordinated long-term research SNS-032 clinical trial programs by individual researchers or collaborative groups are critical if the full potential of Tai Ji Quan to enhance health-related quality of life is to be realized on a broad scale. The work presented in this paper is supported in part by a research grant from the National Institute on Aging (AG034956). “
“Falls and fall-related injuries among older adults (those aged 65 and older) are a substantial Bay 11-7085 challenge to public health worldwide. The world population is aging due to rising life expectancies combined with declining birth rates. Globally, the number of

older persons is growing by 2% per year, considerably faster than the population as a whole. By 2050, the number of persons aged 60 and older in the world will exceed the number of younger adults for the first time in history.1 These changing demographics will increase the pressure on public health organizations and healthcare systems that maintain older adults’ health and quality of life. The reported proportion of older adults who fall each year differs among countries and areas, with estimates of 14% in Taiwan, China,2 15% in Japan,3 30% in the US,4 31% in Mainland, China,2 34% in Chile,5 and 46% in Spain.6 Many types of organizations are working to address this important public health problem including international organizations such as the World Health Organization.

Our results indicated Pfizer Licensed Compound Library that while the inhibition of both evoked and miniature neurotransmission in vglutMN mutants perturbed synaptic development, blocking evoked release alone was not detrimental. We therefore hypothesized that miniature NT could be particularly required for synapse development or alternatively that synapse development relied upon the total amount of NT regardless of whether it was derived from evoked or miniature events. To discriminate between these hypotheses, we sought genetic conditions where miniature NT could be preferentially reduced

versus evoked NT. To do this, we took advantage of the phenomena of synaptic homeostasis that occurs at both Drosophila and mammalian synapses ( Davis, 2013 and Turrigiano, 2012). When postsynaptic ionotropic glutamate receptors (iGluRs) are reduced at Drosophila NMJ synapses, presynaptic terminals increase the number of synaptic vesicles released Alectinib concentration (quantal content) per action potential in order to maintain synaptic strength ( Frank et al., 2006 and Petersen et al., 1997). We exploited this process in mutant combinations where iGluR function was severely inhibited

to specifically reduce miniature NT. As a starting point, we employed iGluR mutants (Schmid et al., 2006) where the expression levels of endogenous glutamate receptor subunits were severely depleted (Figure S3A). In order to avoid disrupting the synaptic scaffolding functions of iGluRs, we combined these mutants with genomic promoter-driven 17-DMAG (Alvespimycin) HCl rescuing transgenes. These transgenes produced either a wild-type glutamate receptor subunit (iGluRWT combination) or a subunit where the glutamate binding region was mutated ( Schmid et al., 2006), rendering the receptor nonfunctional (iGluRMUT combination) ( Figure S3A). Synaptic levels of both iGluRWT and iGluRMUT receptor clusters were similar when

measured using an independent obligate iGluR subunit (dGluRIIC) ( Figures S3B–S3D). We then measured NT in these mutants. iGluRWT terminals had similar miniature NT to controls ( Figures 2A, 2B, 2F, S3F, and S3G). In contrast, iGluRMUT terminals had severely reduced miniature NT with a 96% (p < 0.001) reduction of the mEPSP integral ( Figures 2C, 2F, S3F, and S3G) compared to controls. Miniature NT defects in iGluRMUT mutants were fully rescued by postsynaptic expression of a wild-type iGluR subunit (UAS-dGluRWT) ( Figures 2D and 2F). Though both iGluRWT and iGluRMUT had reduced evoked NT compared to background controls, importantly, they had similar evoked NT to each other ( Figures 2A–2C, 2E, and S3E). As predicted, this was due to an increase in quantal content at iGluRMUT terminals compared to iGluRWT terminals ( Figure S3H). To determine if this homeostatic compensation occurred throughout larval synaptic development, we also measured NT of iGluRWT and iGluRMUT first-instar larval terminals.