The properties of subthreshold sodium current suggest that it can influence the kinetics and amplitude of small EPSPs near typical resting potentials, a prediction that is confirmed using two-photon glutamate uncaging to probe the contribution of sodium currents to single synapse responses. To examine the voltage dependence and gating kinetics of subthreshold sodium current with good voltage control and high time resolution, we used acutely dissociated neurons. To

approximate physiological conditions as nearly as possible, we made MDV3100 in vivo recordings at 37°C and used the same potassium methanesulfonate-based internal solution as in previous current-clamp recordings from the neurons (Carter and Bean, 2009, 2011). Using these conditions to record from mouse cerebellar Purkinje neurons, depolarization by a slow (10mV/s) ramp evoked TTX-sensitive current that was first evident near −80mV and increased steeply with

voltage to reach a maximum near −50mV (black trace, Figure 1A). The TTX-sensitive current evoked by this slow ramp was similar to steady-state “persistent” sodium current previously recorded in Purkinje neurons but activated at considerably more negative voltages than in recordings with less physiological conditions (Raman and Bean, 1997; Kay Selleckchem Anti-cancer Compound Library et al., 1998). In recordings from 26 cells, the TTX-sensitive steady-state current was −16 ± 2 pA at −80mV, −81 ± 16 pA at −70mV, and −254 ± 23 pA at −60mV and reached a maximum of −393 ± 31 pA at −48mV ± 1mV. When converted to a conductance, the voltage dependence of steady-state current could be fit well by a Boltzmann function (Figure 1C) with average next midpoint of −62mV ± 1mV and an average slope factor of 4.9mV ± 0.1mV (n = 26). Slow ramps define the voltage dependence of the steady-state sodium current but do not provide kinetic information about channel activation. Because activation kinetics are important for determining the timing with which sodium current can be engaged by transient

synaptic potentials, we assayed kinetics by applying successive 5mV step depolarizations at the same overall rate as the ramp depolarization (10mV/s, Figure 1A, red traces). As expected, the current at the end of each voltage step reached steady-state and closely matched the ramp-evoked current at that voltage. Unexpectedly, however, there was also a prominent transient phase of sodium current for depolarizations positive to about −70mV. For example, a step from −73mV to −68mV activated a component of transient current nearly as large as the change in steady-state current (Figure 1B). The relative magnitude of the transient current evoked by 5mV steps increased at more depolarized voltages. For a step from −63mV to −58mV, transient current was on average more than three times the size of the change in steady current (−238 ± 62 pA versus −64 ± 6 pA, n = 10).

e., the average time series from the LFPC seed), as well S3I-201 in vivo as six motion parameters as regressors of no interest. To further investigate the results of the PPI analysis, we conducted a conjunction analysis by finding the intersection of voxels that were significant

in the willpower contrast at p < 0.05 whole-brain cluster-level corrected and that also showed significant precommitment-related functional connectivity with LFPC at p < 0.001 uncorrected with an extent threshold of 10 voxels. We tested for statistical significance using small-volume correction (p < 0.05, family-wise error corrected at the cluster level) in a priori regions of interest (ROIs) identified from the literature in DLPFC, IFG, PPC, and LFPC (Table S8). ROI masks were constructed as bilateral 10 mm spheres centered on peak coordinates from previous studies of value-based decision making (Supplemental

Experimental Procedures). We also note results outside our regions of interest that survive whole-brain cluster-level corrections. Images are displayed at a threshold of p < 0.005, k > 10 to show the extent of activation in the significant clusters. Results are reported using the MNI coordinate system. For the ROI analyses, we extracted contrast-specific parameter estimates for each ROI (identified from the literature, as above). To test for the effects of condition on responses in each ROI, we conducted repeated-measures ANOVA on the parameter estimates in SPSS v21. One subject was excluded from this analysis for having parameter estimates more than two SDs higher http://www.selleckchem.com/products/s-gsk1349572.html than the group mean. For the cross-region comparison ANOVA, we were not interested in differences in average parameter estimates across regions but rather in the within-region differences across tasks. We therefore first z transformed the parameter estimates for each region separately by subtracting each region × task parameter estimate from the mean parameter estimate for that region (collapsed across tasks) and dividing by the SD of the parameter estimates

for that region across tasks. For the mediation analysis, Carnitine palmitoyltransferase II we used hierarchical linear regression as outlined in Baron and Kenny (1986). Indirect effects in the mediation model were estimated using the SPSS procedure described in Preacher and Hayes (2004). All parameter estimates used in the mediation analyses were extracted from coordinates derived from previous studies (Table S8) to avoid nonindependence issues. vmPFC parameter estimates were extracted from the Precommit > Opt-Out LL contrast. DLPFC parameter estimates were extracted from the PPI contrast (the interaction between the neural activity in the LFPC seed and a vector coding for the main effect of decision type [1 for Precommitment, −1 for Opt-Out LL]). M.J.C. is supported by the Sir Henry Wellcome Postdoctoral Fellowship. T.K.

We found that FLRT3 was not sufficient to induce clustering of synapsin in axons in this heterologous cell assay ( Figures S2D and S2E) but that LPHN3-expressing HEK293 cells did cluster PSD95 in contacting dendrites, though less potently than NRXN1β(-S4) ( Figures S2F and S2G). After DNA Synthesis inhibitor establishing

that the latrophilin ligand FLRT3 is expressed in hippocampal neurons and localizes to glutamatergic synapses, we decided to test whether the interaction of endogenous LPHN3 with its ligand is of functional importance. We applied excess soluble ecto-LPHN3-Fc protein to dissociated hippocampal cultures to competitively disrupt endogenous LPHN3 complexes and analyzed glutamatergic synapses on dentate granule cells (GCs) (identified by nuclear Prox1 immunoreactivity; Williams et al., 2011) by immunofluorescence (Figure 3A). We found that ecto-LPHN3-Fc treatment strongly reduced the density of synaptic puncta (Figure 3B) without affecting their size (Figure 3C). These results suggest that reducing the availability

of LPHN3 ligands such as FLRT3 by competition with ecto-LPHN3-Fc prevents glutamatergic synapses from developing properly. If ecto-LPHN3-Fc exerts its effect by disrupting the interaction of LPHN3 with FLRT3, loss of postsynaptic FLRT3 might be expected to result in a similar reduction in synapses. We designed a short hairpin RNA (shRNA) to specifically knock down Flrt3 expression (shFlrt3) and click here verified its efficacy and specificity ( Figures

S3A–S3C). To determine whether endogenous FLRT3 regulates synapse number, we electroporated postnatal day 0 (P0) hippocampal cultures with shFlrt3 or control plasmids to sparsely knock down FLRT3 and analyzed synapses formed onto GC dendrites by immunofluorescence ( Figure 3D). We observed a large decrease in the density of synapses with shFlrt3 ( Figure 3E), an effect similar to that observed with ecto-LPHN3-Fc treatment. This decrease in synapse number was fully rescued by coelectroporation with an shRNA-resistant Bumetanide FLRT3 construct (FLRT3∗-myc) ( Figures 3E and S3A). Additionally, we saw a small decrease in the area of synaptic puncta following FLRT3 knockdown ( Figure 3F). To see whether the decrease in synapse density assessed by immunofluorescence corresponds to a decrease in functional synapses, we recorded miniature excitatory postsynaptic currents (mEPSCs) from putative GCs in similar cultures ( Figure 3G). Consistent with the reduction in synaptic puncta density, we found a marked decrease in mEPSC frequency ( Figure 3H) and a slight decrease in the mean amplitude of mEPSCs ( Figure 3I) after FLRT3 knockdown. These experiments together suggest that a loss of FLRT3 in postsynaptic GCs reduces the number of excitatory synapses onto those neurons.

, 1980) in spherical coordinates (Supplemental Experimental Procedures, available online). Second, we used low-magnification two-photon calcium imaging to measure the retinotopic organization of visual cortex at high resolution. This resulted in a retinotopic map which was continuous within the extent of visual cortex and allowed us to precisely define borders between several areas based on visual field sign reversals at peripheral representations (Sereno et al., 1995; Figure 1 and Figure 2). A representative intrinsic imaging map from one animal is shown in Figure 1. Several features of previous

map schema are present in the map (for a direct comparison, see Wagor et al., 1980, Figure 4, and Wang and Burkhalter, 2007, Figure 10). Our data are most consistent with the map predicted primarily from anatomy by Wang

and BVD-523 cost Burkhalter (2007), and thus all further analyses and discussion are made in reference to their schema and area selleck kinase inhibitor names. Intrinsic imaging maps were sufficient to detect activation in V1, LM, LI, AL, RL, A, AM, PM, P, and POR, but often could not resolve fine-scale details in the maps of relatively small areas (such as LI, RL, A, AM, and PM) that were necessary to precisely define area boundaries. Using the intrinsic imaging maps as a guide, several calcium dye loadings were performed to load a volume of cortex spanning several millimeters and encompassing several visual areas (Experimental Procedures). We then systematically imaged Oxalosuccinic acid the extent of the loaded area by moving the objective in ∼500–700 μm steps to tile the whole loaded region. At each position, we displayed the retinotopic mapping stimulus (identical to that used for intrinsic imaging) to the animal, and mapped the retinotopy of that ∼800–1000 μm2 patch of cortex

with a 16× objective. Mosaics of these individual maps resulted in a complete high-resolution map of the region, often spanning several millimeters and encompassing the full visuotopic extent of several extrastriate visual areas (Figure 2 and Figure S2). At this resolution, we observed several features in the maps that were not seen with intrinsic imaging, revealing the fine-scale organization of each of eight extrastriate visual areas predicted previously (LM, LI, AL, RL, AM, PM, P, and POR; Figure 2 and Figure S2). We observed some retinotopic structure in the putative location of area A, but did not target this area for population analysis because its retinotopic map was ambiguous in relation to its predicted organization (Wang and Burkhalter, 2007; Figure 2 and Figure S2). It was also difficult to obtain complete maps of areas P and POR given their cortical location (Figure S2). Using this method, we located the region of cortex representing the central visual field within each confidently identified area (∼0 degrees azimuth, ∼20 degrees altitude) for further analysis.

, 1993). IL-4 and IL-13 are frequently studied because they may be the first genes to have increased DNA Damage inhibitor levels in response to extracellular

parasites, leading to Th2 polarization (Else and Finkelman, 1998) and resistance to animals (Zaros et al., 2010). In this study, the IL-4 mRNA levels in the abomasal lymph node of the infected group were up-regulated 14-fold in comparison to the control group (Fig. 2). Similar results were obtained by (Canals et al., 1997), who observed a significant up-regulation of IL-4 abomasal lymph node of Bos taurus cattle infected with O. ostertagi on the fourth day post primary infection, increasing gradually until the 28th day of infection. Claerebout et al. (2005) observed an increase in the expression of IL-4 and IL-10 in lymph nodes of immunized calves also infected with O. ostertagi, after 3 weeks of infection. In contrast, in the present study we found no difference in this interleukin in the abomasal mucosa, corroborating the results obtained by www.selleckchem.com/products/bgj398-nvp-bgj398.html ( Li et al., 2007) and contrasting with those of Lacroux et al. (2006), studying sheep (which are more sensitive to this nematode infection). IL-13 acts in parasitic infections to promote allergic response, mast cell increase and IgE production, among other reactions. In the present work, severe induction of IL-13 mRNA in abomasal lymph node was observed,

about 30 times higher in the infected than Mephenoxalone in the control group (Fig. 2). In the abomasal mucosa, IL-13 expressed the same pattern, with a fivefold increase in the infected group compared with the control group (Fig. 3). Bancroft et al. (1998), studying knockout mice for IL-13, observed susceptibility to T. muris infection as well as a decrease in the response of other Th2 cytokines, inhibiting the expulsion

of the parasites. An increase of IL-13 was also observed in sheep immunized and infected primarily with H. contortus ( Lacroux et al., 2006), showing this cytokine is essential in the protection against gastrointestinal nematode infection. In fact, some IL-4 and IL-13 functions are redundant, conferring protective response, resistance and expulsion of the parasites (Else and Finkelman, 1998). We showed that IL-13 had a strong up-regulation, in both tissues, indicating this cytokine could be a precursor of IL-4, stimulating its increase and probably the protective response in the early infection stage in Nellore cattle. This is possible because it has been found that IL-4 starts to increase in the fourth day post-infection of calves with O. ostertagi ( Canals et al., 1997). There is little data about this polarization in zebu cattle, but it is clear that both cytokines are expressed synergistically and are essential to control this infection.

Neuronal circuitry underlying attraction to BZ, BU, and IAA includes AWC sensory neurons and ∼20 interneurons and motor neurons. Thus, expression of RGEF-1b-GFP in a few neurons might restore chemotaxis in rgef-1−/− animals. Three promoters were used to drive RGEF-1b-GFP expression.

The odr-1 promoter is see more active in AWC, AWB, and I1 neurons; odr-3 drives transcription in AWA, AWB, AWC, and four other neurons, and the gpa-3 promoter is silent in chemosensory neurons, but active in a dozen distinct neurons ( L’Etoile and Bargmann, 2000 and Lans et al., 2004). An odr-1:: RGEF-1b-GFP transgene restored CI values to near-WT levels in rgef-1−/− animals ( Figures 3E and 3F). Substantial, but incomplete rescue of chemotaxis ABT-199 was achieved with an odr-3::REGF-1b-GFP transgene. Partial restoration of chemotaxis may be due to lower transcriptional activity of odr-3 relative

to odr-1 and rgef-1 promoters. Although the gpa-3 promoter enables RGEF-1b-GFP accumulation in multiple neurons, the rgef-1−/− phenotype persisted ( Figures 3E and 3F). I1, AWB and AWA neurons are not involved in BZ- or BU-induced chemotaxis. Thus, the results suggest that RGEF-1b GTP exchange activity in AWC sensory neurons is indispensable for activating neuronal circuitry underlying chemotaxis behavior. The observations establish a neuron-specific physiological role for a RasGRP. Conserved Arg290 in the RGEF-1b catalytic domain was mutated to Ala (Park et al., 1994). RGEF-1bR290A protein accumulated in transfected cells, but did not promote loading of GTP onto LET-60 (Figure 4A, lanes 3 and 4). Cells expressing bombesin receptor were cotransfected with transgenes encoding WT RGEF-1b (0.2 μg DNA), Flag-LET-60

(1 μg DNA), and RGEF-1bR290A (plasmid DNA varied from 0–1 μg). In both bombesin-treated and unstimulated cells, LET-60-GTP content decreased as the ratio Etomidate of RGEF-1bR290A cDNA:WT RGEF-1b cDNA increased (Figure 4B, lanes 1–8). A 4-fold excess of RGEF-1bR290A transgene eliminated bombesin-induced GTP exchange activity of WT RGEF-1b (Figure 4B, lanes 7 and 8). Thus, RGEF-1bR290A is a dominant-negative RasGRP. Expression of RGEF-1bR290A-GFP throughout the nervous system did not rescue chemotaxis in rgef-1−/− animals ( Figure 4C). Thus, RGEF-1b does not function as a scaffold in vivo; its GTP exchange activity is required for chemotaxis. Moreover, Arg290 was identified as an essential amino acid in the catalytic domain. Expression of RGEF-1bR290A-GFP in the WT background suppressed chemotaxis to odorants detected by AWC neurons ( Figure 4D). The data show that RGEF-1b is essential for odorant-activated chemotaxis in a WT context. By analogy with mammalian Ras and Rap1 mutants (Campbell et al., 2006), substitution of Gly12 with Val should ablate GTPase activity, thereby locking LET-60 or RAP-1 in an active, GTP-bound state (Figure 5A). Replacement of Ser17 with Asn should generate dominant-negative mutants of LET-60 and RAP-1.

Although the sharpness and the stability of border fields show some increase from young to adult age, the basic properties of border cells HDAC inhibitor appear to be present from the outset. In particular, when a wall is inserted in parallel with the original peripheral firing field, the cells develop new firing fields along the insert, just as in adult rats. Head direction cells were also present from the outset. In contrast, grid cells, recorded in the same animals,

matured slowly, showing only minimal spatial periodicity during the first week of outbound exploration. The slow maturation of the grid cells and the fast expression of directional modulation confirm previous observations (Langston et al., 2010 and Wills et al., 2010). The presence of border cells in the immature MEC has implications for mechanisms of place cells. Place cells receive the majority of their cortical inputs from the entorhinal cortex (Witter and Amaral, 2004). Spatial signals are thought to originate primarily in the medial part of the entorhinal cortex (Fyhn et al., 2004, Hafting et al., 2005 and Hargreaves et al., 2005). The fact that the majority of hippocampus-projecting spatially modulated cells in this area are grid cells (Sargolini et al., Entinostat mw 2006 and Zhang et al., 2013) has raised the possibility that place cells emerge

by transformation of inputs from grid cells. One class of models relies on linear summation of impulses from cells with different grid spacing but similar grid phase and grid orientation (O’Keefe and Burgess, 2005, Fuhs and Touretzky, 2006, McNaughton et al., 2006 and Solstad et al., 2006). However, these models cannot readily account for the fact that place cells mature faster than grid cells in developing animals (Langston et al., 2010 and Wills et al., 2010), although with the addition of local circuit

mechanisms and Hebbian plasticity, second weakly modulated and irregular spatial inputs would in principle be sufficient to generate discrete and stable place fields (Rolls et al., 2006, de Almeida et al., 2009, Savelli and Knierim, 2010 and Monaco and Abbott, 2011). The present findings point to border cells as an alternative source of spatial information to the hippocampus of young animals, possibly with head direction cells as an additional source of modulation. Only a small fraction of the entorhinal cell population has properties defining them as border cells but retrograde labeling suggests that the hippocampal projections of these cells may be as dense as those of the more slowly developing grid cells (Zhang et al., 2013). The present study, in conjunction with the retrograde labeling study, suggests that these projections may be present from young age. Place cells may thus be formed by inputs from both grid cells and border cells but in the immature nervous system the border cells may provide the most reliable spatial inputs.

A majority (40%) had been running barefoot for greater than 1 year, with 23% of respondents between 6 months and 1 year, and 23% for 2–6 months. Only 6% of runners who partook

in the survey had tried barefoot running for less than 1 month (Fig. 2). Over 94% of participants incorporated some type of barefoot running into their weekly mileage. The majority of respondents ran only a small portion of their running barefoot, with 34% running less than 10%; however, 16% of participants ran 100% of their running barefoot (Fig. 3). The respondents ran barefoot on a variety of surfaces including grass (60%), city streets (55%), sidewalks (55%), trail (42%), and treadmills (19%). Respondents were allowed to select multiple surfaces, leading to totals equaling greater than 100% (Fig. 4). A majority of the participants KU-57788 molecular weight (53%) viewed barefoot running as a training tool to improve specific aspects of their running. However, close to half (47%) viewed barefoot training as a viable BTK inhibitor cost alternative to shoes for logging their miles (Fig. 5). Forty-two percent of respondents used minimalist shoes as part of their running shoe rotation, with 17% of respondents using them for 25%–75% of their runs, and 19% of the runners using them for less than 25% of their runs, 5% of respondents had plans to purchase a minimal shoe in the near future, and 17% did not use a minimal shoe in their training (Fig. 6). A

majority of runners (55%)

who participated in the study found no or slight performance benefit secondary to barefoot running. Over 39% of the runners found moderate to significant improvements in their race times. However, only 6% of respondents claimed to have gotten slower after starting barefoot training (Fig. 7). A large majority (64%) of runners participating in the study experienced no new injuries after starting barefoot running. Those who did experience Terminal deoxynucleotidyl transferase injuries mostly suffered foot (22%) and ankle (9%) problems (Fig. 8). Thirty-one percent of all respondents had no injury prior to starting barefoot running. A large amount of runners (69%) actually had their previous injuries go away after starting barefoot running. Runners responded that their previous knee (46%), foot (19%), ankle (17%), hip (14%) and low back (14%) injuries all proceeded to improve after starting barefoot running (Fig. 9). The data revealed that most respondents (55%) experienced Achilles or foot pain when they initially began the transition to barefoot running. However, 47% of these runners found that it resolved and went away fairly quickly. Only 8% of these runners had Achilles or foot pain develop into a chronic injury. A large percentage of respondents (45%) never experienced Achilles or foot pain during the transition to barefoot running (Fig. 10). This survey is the first study to obtain data on barefoot running and injuries.

gondii by ultrastructural analysis are associated with damage to cellular membranes, such as mitochondrial swelling and rupture of the parasite plasma membrane. Another possibility, which deserves further investigation, is that azasterols may have an effect on methylation during phospholipid biosynthesis ( Palmié-Peixoto et al., 2006). Similarly, the effect of azasterols against

the bloodstream form of Trypanosoma brucei rhodesiense, which utilises host sterols ( Coppens and Courtoy, 2000), also demonstrated that, these compounds can inhibit the growth of these protozoa by a mechanism of action other than inhibition of ergosterol biosynthesis selleck chemicals llc ( Gros et al., 2006b). Our results demonstrate that azasterols are very active and selective against T. gondii in vitro and suggest further investigation of this class of molecules as potential agents against toxoplasmosis. This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) and Programa de Núcleos

de Excelência-Pronex-Faperj-CNPq. “
“Acetylcholinesterase (AChE; EC 3.1.1.7) is a key enzyme in the nervous system, responsible for the rapid hydrolysis of the neurotransmitter acetylcholine at cholinergic synapses (Rosenberry, 1975). Organophosphate compounds (OP) target the AChE enzyme as its primary site of action, phosphorylating the active site serine to block the hydrolysis of acetylcholine, leading to the death of the insect (Menozzi et al., 2004). Point mutations in the AChE gene Androgen Receptor Antagonist purchase have been described for resistant strains of different dipteran species (Mutero et al., 1994, Walsh et al., 2001, Vontas et al., else 2002 and Temeyer et al., 2008). Most of these mutations in the AChE gene are conserved in these species and combinations of several point mutations in this enzyme have already been found in several alleles, where they induced higher levels of organophosphate resistance (Mutero et al., 1994). The New World screwworm (NWS), Cochliomyia hominivorax, is one of the most

important myiasis-causing flies in the Neotropics, characterized by the ability of its larvae to develop in the flesh of vertebrates, causing severe economic losses to livestock industry ( Hall and Wall, 1995). Although the Sterile Insect Technique (SIT) was successful for NWS eradication in North and Central America ( Galvin and Wyss, 1996), throughout its current geographical distribution the control of this species has relied on the application of chemical insecticides, which normally leads to the selection of resistant individuals. Although there are few reports regarding resistance in NWS ( Veríssimo, 2003, Coronado and Kowalski, 2009 and Robinson et al., 2009), mutations in the carboxylesterase E3 gene are shown to involve a general form of OP resistance in Lucilia cuprina ( Newcomb et al., 1997) and Musca domestica ( Claudianos et al.

Neuroligins (NLGs) are postsynaptic adhesion molecules that bind presynaptic neurexins (NRXs) with nanomolar affinity (Südhof, 2008). Rodents have four NLG isoforms, each exhibiting a specific expression pattern and subcellular Autophagy inhibitor molecular weight distribution. In particular, NLG1 and NLG2 are localized to excitatory and inhibitory synapses, respectively (Graf et al., 2004). NLGs and NRXs contain intracellular domains that interact with scaffold proteins,

such as PSD95 and CASK (Südhof, 2008). Adhesion between NLGs and NRXs thus provides a structural bridge between pre- and postsynaptic scaffolding machinery. In humans, NRXs and NLGs have been strongly linked to autism spectrum disorders, emphasizing the importance of this transsynaptic complex for normal brain development (Südhof, 2008). Indeed, NLGs induce functional maturation of presynaptic terminals (Dean et al., 2003; Scheiffele et al., 2000; Wittenmayer et al., 2009), whereas NRXs cluster postsynaptic proteins (Graf et al.,

2004; Heine et al., 2008). Their Galunisertib ic50 ability to transaggregate synaptic components implicated NLGs and NRXs as critical mediators of synapse formation. This hypothesis was supported by in vitro studies showing that NLG levels correlate with the number of synapses generated during development (Chih et al., 2005; Dean et al., 2003; Graf et al., 2004; Levinson et al., 2005). However, NLG1-NLG3 triple knockout (KO) neurons exhibit normal synapse number and ultrastructural synaptic features, but present severe deficits in synaptic transmission (Varoqueaux et al., 2006),

indicating that, in vivo, NLGs are not required Oxymatrine for the initial stages of synaptogenesis, but are critical for proper synaptic function. Recent studies have further shown that NLGs regulate NMDA (Chubykin et al., 2007; Jung et al., 2010) and AMPA (Etherton et al., 2011; Heine et al., 2008; Shipman et al., 2011) receptor function and are involved in multiple forms of synaptic plasticity across species (Choi et al., 2011; Jung et al., 2010). Interestingly, overexpression of NLG1 in hippocampal slices and cultured neurons increases release probability through NRX-dependent mechanisms (Futai et al., 2007; Ko et al., 2009; Stan et al., 2010), whereas disruption of endogenous NLG-NRX interactions with soluble Fc-NRX fragments decreases miniature excitatory postsynaptic current (mEPSC) frequency and release probability (Levinson et al., 2005). In vivo, transgenic expression of NLG1 results in extended active zones and increased number of reserve pool vesicles (Dahlhaus et al., 2010), while neurons lacking αNRX1-αNRX3 exhibit deficits in synaptic transmission due to impaired N-type Ca2+ channel function (Missler et al., 2003). These results suggest that the NLG-NRX transsynaptic complex is an important regulator of presynaptic function. However, a limitation of most studies to date is the reliance on long-term manipulations susceptible to indirect compensatory mechanisms.