Each fly was tethered to a tungsten wire with UV-cured glue and suspended within an electronic visual flight simulator consisting of a 32 × 88 cylindrical array of green LEDs ( Reiser and Dickinson, 2008). The amplitude and frequency of the fly’s wing beats were monitored with an optical wing-beat analyzer, allowing us to present visual stimuli in either open- or closed-loop mode ( Götz, 1987). All visual stimuli are described in the

Supplemental Experimental Procedures and depicted in Figure S2. Each 3 s open-loop stimulus HA-1077 in vitro condition was followed by 3.5 s of closed-loop “stripe fixation” to ensure that flies were actively steering at the onset of each trial. Within an experiment, each set of conditions was presented as random blocks repeated three times. Trials in which the fly stopped flying were repeated at the end of each block. These data were averaged on a per fly basis to produce a mean turning response for each stimulus condition. Further details of the all methods used are provided in the Supplemental Experimental Procedures. We thank Barret Pfeiffer, Heather Dionne, and Chris Murphy for molecular biology of Split-GAL4 constructs, Teri Ngo and Ming Wu for assistance

with Split-GAL4 screening, the Janelia Fly Core selleck screening library for assistance with Drosophila care, the Janelia Fly Light Project for providing images of the primary GAL4 lines and of C2 single neurons, the Janelia Fly Light Scientific Computing Team for image processing software, Matt Smear and Stephen Huston for assistance with stimulus design, Damon Clark for discussions of L1- and L2-inactivation phenotypes, and Magnus Karlsson and Jinyang Liu for continued development and support of the visual display system. The Iso-D1 and the two L1 stocks used in Figure S6 were a gift from Tom Clandinin. We also thank Larry Zipursky, Alla Karpova, Stefan Pulver, Vivek Jayaraman, Anthony Leonardo, and members of the Reiser, Jayaraman,

Card, and Rubin laboratories. This project was supported by HHMI. “
“In natural environments, important sensory stimuli are accompanied by competing and often irrelevant sensory events. Although simultaneous sensory signals can obscure one another, animals are adept at extracting important signals from noisy Thiamine-diphosphate kinase environments using a variety of sensory modalities (Born et al., 2000, Jinks and Laing, 1999, Raposo et al., 2012 and Wilson and Mainen, 2006). As a striking yet common example of this perceptual ability, humans and other vocally communicating animals can recognize and track individual vocalizations in backgrounds of conspecific chatter (Cherry, 1953, Gerhardt and Klump, 1988 and Hulse et al., 1997). The ability to extract an individual vocalization from an auditory scene is thought to depend critically on the auditory cortex (Näätänen et al., 2001).

39 Rather than a priori determination of high-risk groups, the use of a tool to predict postoperative pulmonary complications to improve the specificity of preoperative inspiratory muscle training should be considered. It is important to note that the diagnosis of postoperative pulmonary complications remains contentious; given the lack of consensus on a standard

definition. 6 This lack of consensus increases the observed variability in the incidence MDV3100 in vitro of postoperative pulmonary complications. In this review, one study did not report on the methods used to diagnose postoperative pulmonary complications, 35 four studies used a combination of clinical signs and diagnostic imaging, 17, 26, 27 and 28 and one study identified the presence of postoperative pulmonary complications using diagnostic imaging alone. 18 Only two studies used standardised methods and operational definitions that had been previously described in the literature. 27 and 29 This discrepancy in measurement is representative of the broader literature 6 and makes comparison between studies difficult. Until a gold-standard operational CRM1 inhibitor definition

for postoperative pulmonary complications is used consistently, the literature should be interpreted with caution, including the results of this review. Studies investigating the effects of preoperative physical exercise programs could not be included in the meta-analyses because the data were insufficient. Hence, the results of the presented analyses can only be generalised to interventions that include breathing exercises and/or education. It is possible that physical training may have a greater effect on patient outcome than education, because education has been shown not to provide additional benefit over physical training in some populations40 and the study by Arthur et al21 demonstrated that preoperative physical training reduced length of stay. There were conflicting findings about

the benefit of exercise training on length of stay in ICU and aminophylline in hospital, so caution should be applied to these findings and to the finding that exercise training impacts on time to extubation, because only one study addressed this important issue.16 Further high-quality randomised controlled trials should be conducted to establish the effectiveness of preoperative exercise training on these outcomes. Only two studies measured objective postoperative physical outcomes20 and 29 and it is a limitation of the included studies that objective, functional measures such as the six-minute walk test were not used. Not only is the six-minute walk test a valid and reliable measure of functional capacity in a cardiac rehabilitation population,41 but it is a commonly used, inexpensive and safe test of cardiovascular endurance in cardiac surgery populations.

To determine the extent and duration of suppression of mutant huntingtin synthesis achievable with ASO infusion into the nervous system, a 20-mer phosphorothioate modified oligonucleotide complementary to human huntingtin mRNA (HuASO) and containing 2′-O-(-2-methoxy) ethyl modifications on the five nucleotides on the 3′ and 5′ ends to increase its stability, tolerability and potency (Bennett and

Swayze, 2010, Henry et al., 2001 and Yu et al., 2004) was infused continuously (10, 25, or 50 μg/day) for 2 weeks into the right lateral ventricle of the BACHD mouse model of HD. BACHD mice harbor a full-length mutant human see more huntingtin gene with an expansion of 97 CAG/CAA repeats and express the mutant protein at approximately 1.5 times the level of the endogenous mouse huntingtin (Gray

et al., 2008). Infusion of the HuASO significantly decreased the levels of human huntingtin mRNA in a dose-dependent manner (Figure 1A) (25 μg/day, to 42% of the level of vehicle alone [p = 0.007]; 50 μg/day, to 28% vehicle [p = 0.005]). For all subsequent studies a dose of 50 μg/day of HuASO was used. At the end of infusion, the ASO had accumulated to significant levels (170 ± 16 μg/g brain tissue) that then decreased CP-868596 in vivo in abundance with approximately first order kinetics over a subsequent 16 week period (Figure 1B). This pharmacokinetic profile is similar to that observed in peripheral tissues following systemic administration of similarly modified ASOs (Yu et al., 2001). At all times postinfusion, more than 90% of the remaining ASO was full length, as judged by capillary gel electrophoresis, indicating the ASO was chemically stable within cells of the nervous system. A significant reduction in human huntingtin mRNA levels (reduced to 38% ± 3% [p < 0.001] Tolmetin of the vehicle-infused animals) was observed at the earliest time point (after 2 weeks of continuous infusion). This

reduction persisted for 12 weeks, rising back to untreated levels only 16 weeks after the termination of treatment (Figure 1C). At 12 weeks posttreatment, only 13 μg/g of ASO was present in the brain (Figure 1B), yet huntingtin reduction persisted, indicating that low doses of ASO in the correct cellular compartments are sufficient to be effective and are maintained with long in vivo half lives, particularly in the brain where many of the cells are nondividing. A similar pattern of reduction was observed for the accumulated mutant human huntingtin protein; however, the reduction was delayed relative to the mRNA (Figure 1D), reflecting a longer half-life of the protein than the mRNA. Nevertheless, by 4 weeks posttermination of ASO infusion, mutant human huntingtin protein levels were reduced by two-thirds and gradually returned to untreated levels 16 weeks after the end of infusion (Figure 1D).

, 1999 and Trommsdorff et al., 1999). After development, the production of Reelin is dramatically decreased but remains prominent in GABAergic interneurons (Alcántara et al., 1998) of the cortex and hippocampus (Pesold et al., 1998). In mature neuronal circuitry, Reelin modulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor activity by postsynaptic activation of ApoER2 and VLDLR ( Beffert et al., 2005 and Qiu et al., 2006). The interaction between Reelin and its receptors leads to a signaling cascade initiated by phosphorylation of disabled-1 (Dab-1) that in turn leads to activation of Src, Fyn, NVP-BGJ398 price or PI-3 kinases ( Kuo

et al., 2005 and Trommsdorff et al., 1999). Here, we demonstrate that Reelin also

acts presynaptically in mature neurons to rapidly enhance spontaneous neurotransmitter release without detectable alterations in the properties of evoked neurotransmission. This action of Reelin depended on the function of the vesicular Protein Tyrosine Kinase inhibitor SNARE protein VAMP7 but not syb2, VAMP4, or vti1a. This finding demonstrates an example where an endogenous neuromodulator relies on the diversity of SV pool-associated SNAREs and selectively mobilizes a subset of vesicles independent of electrical activity. To assess the effect of Reelin on neurotransmitter release, we applied Reelin (5 nM) to hippocampal neurons and recorded spontaneous miniature postsynaptic currents in the presence of tetrodotoxin (TTX) to block APs. Using whole-cell voltage clamp recordings, we monitored pharmacologically isolated excitatory postsynaptic currents (mEPSCs) generated by activation of AMPA or NMDA receptors as well as GABAergic miniature inhibitory postsynaptic currents (mIPSCs) for 5 min in normal Tyrode’s solution. Reelin was then perfused into the chamber and mPSCs were

measured for at least 5 min followed by washout of Reelin (Figure 1). either Reelin robustly increased the frequency of spontaneous AMPA mEPSCs (Figure 1B) from 0.8 ± 0.1 Hz up to 4.8 ± 0.2 Hz during Reelin (∼6-fold increase with t1/2 = 67.6 ± 14.4 s). This effect was dependent on acute Reelin application as upon Reelin removal, spontaneous event frequency returned to baseline levels (0.9 ± 0.2 Hz with t1/2 = 75.1 ± 23.3 s). Similarly, Reelin increased the frequency of both NMDA-derived mEPSCs (from 0.7 ± 0.1 Hz before Reelin to 3.2 ± 0.3 Hz during Reelin and 0.7 ± 0.1 Hz after Reelin washout, ∼4.5-fold increase with a rise time of t1/2 = 43.1 ± 21.0 s and a decay time of t1/2 = 26.1 ± 7.5 s) and GABA-mediated mIPSCs (from 0.4 ± 0.04 Hz before Reelin to 1.7 ± 0.1 Hz during Reelin and 0.4 ± 0.1 Hz after Reelin washout, a ∼4-fold increase with a rise time of t1/2 = 17.0 ± 4.8 s and decay time of t1/2 = 37.1 ± 15.1 s) (Figures 1C and 1D). In all cases, the elevated spontaneous release frequency was sustained for longer than 5 min in the presence of Reelin (Figure 1E).

4483; Figure 6F). Furthermore, unpolarized

UV light presented from the zenith to unshielded eyes did not result in neuronal response amplitudes above background level over the 360° of rotation ( Figure S2), underscoring the hypothesis that indeed changing E-vectors cause the observed frequency modulations in response to polarized UV light from zenithal stimulation. Although many insects have a DRA that is anatomically and functionally distinct from the other regions of the retina (Labhart and Meyer, 1999), our results are unique in that they show that the dorsal eye is not required for DAPT clinical trial mediating the azimuth-dependent responses in single neurons to unpolarized light spots but is essential click here for zenithal E-vector responses. Thus, skylight orientation information from two distinct regions of the compound eye is integrated

in the individually recorded neurons—the dorsal eye (including the DRA) for polarized UV light responses and the laterally directed main retina for unpolarized light responses. It remains possible that polarized colored light spots presented to the lateral retina of monarchs can also elicit neuronal responses ( Kelber, 1999), but this issue could not be examined given the constraints of our recording system. However, intracellular recordings of photoreceptors in the other regions of the monarch retina show low polarization sensitivity compared to the high sensitivity found in the DRA ( Stalleicken Thymidine kinase et al., 2006). After describing the response characteristics of neurons to individual compass-related stimuli (polarized and unpolarized light), we analyzed the relation between E-vector tuning and azimuth tuning for the recorded cells from migratory monarchs. The expectation was that there would be a 90° difference between E-vector tuning and azimuth tuning within individual neurons, because polarized light was applied from the zenith ( Wehner and Labhart, 2006) ( Figures 1A and 1B). As described above, the azimuth tuning in response to unpolarized colored light spots was independent of the

stimulation wavelength used. Accordingly, when considering all neurons recorded from the vicinity of the left LAL (i.e., excluding the two later stage neurons from the PB), the absolute azimuth tunings for all unpolarized light responses were tightly clustered (Figures 7A–7C). Of the 24 neurons responding to unpolarized light spots, 22 exhibited azimuth tunings on the right side of the animal (256° ± 13.5°, mean ± standard deviation [SD]). Surprisingly, there was great variability of E-vector tunings in these cells, such that no clear common tuning angle was observed (n = 23) ( Figures 7D and 7E). Moreover, there was no correlation between the E-vector tuning and azimuth tuning within individual neurons, as revealed by the analysis of the difference angles between the two tunings (ΔΦmax values).

g., Engert et al., 2002; Kohn and Movshon, 2004). While it was recently shown that On-Off DSGCs project to the dorsal

lateral geniculate nucleus (dLGN, Huberman et al., 2009), the role of DSGCs in establishing directional responses in the dLGN and in the striate cortex (V1) is not known. Our findings raise the Buparlisib datasheet possibility that direction-selective plasticity in higher-order visual structures relies upon input from a combination of stable and reversed DSGCs. Indeed, almost 50 years ago, Barlow and Hill (1963) had proposed that a mixture of DSGCs encoding different preferred directions underlies higher-order perceptions of motion and that alterations in the balance between DSGCs provides a physiological explanation for long-lasting motion illusions (for example, Masland, 1969). We used transgenic mouse lines that express GFP in posteriorly tuned On-Off DSGCs, DRD4-GFP and TRHR-GFP, (Huberman et al., 2009; Rivlin-Etzion et al., 2011) and wild-type mice (C57BL/6). Loose-patch two-photon-targeted

recordings from GFP+ cells (Wei et al., 2010) were performed Sirolimus in vitro from mice of either sex between postnatal day 14 (P14) and P88. Visual stimulation was transmitted through a 60× objective (Olympus LUMPlanFl/IR360/0.90W) and stimulated a field of ∼225 μm in diameter. The directional preference of DSGCs was determined using a DS test: 3 s moving gratings in 12 different directions (900 μm/s, 225 μm/cycle). Each direction was repeated three to five times in a pseudorandom order (for DS test variations, see text). Cells from DRD4-GFP and TRHR-GFP mice exhibited a comparable degree of direction preference reversal and were therefore combined for all analyses. We thank Frank Werblin, Andrew Huberman, Justin Elstrott, and members of the Feller laboratory for reading a previous version of this manuscript. NIH-sponsored

Mutant Mouse Regional Resource Center (MMRRC) National System provided genetically altered DRD4-GFP (000231-UNC) and TRHR-GFP (030036-UCD) mice. This work was supported by grants RO1EY019498 and RO1EY013528 from the National Institutes of Health. M.R.-E. was supported by the Ketanserin Human Frontier Science Program, the National Postdoctoral Award Program for Advancing Women in Science, and by the Edmond and Lily Safra (ELSC) Fellowship for postdoctoral training in Brain Science. “
“Structured neuronal activity spanning subcortical and cortical regions supports the integration and organization of recently learned information into stable, consolidated memory during sleep (see Diekelmann and Born, 2010). The extent to which distinct sleep stages and neurophysiological features differentially contribute to dissociable mnemonic processes remains unclear, but converging evidence indicates that cortical slow-waves, thalamocortical sleep spindles and hippocampal ripples during non-REM (NREM) sleep act in concert to preferentially support memory consolidation.

To explore what influences motor neuron function prior to neurodegeneration, Mentis et al. (2011) examined the primary afferent input and found that loss of

synaptic input from sensory spindle afferents followed the temporal and topographic pattern of later motor neuron loss. Treatment with a histone deacetylase inhibitor, an intervention that improves motor function in this mouse model, also improved synaptic input from muscle spindle afferents (Mentis et al., 2011). Since a treatment that prevents reduction of the muscle MK-2206 manufacturer spindle afferents also ameliorated motor neuron loss, this paper suggests that that loss of afferent input may contribute to eventual motor neuron degeneration in SMA. A second example of decreased synaptic input contributing to neurodegeneration involves the spinocerebellar ataxias (SCAs), a group of neurodegenerative

disorders that predominantly affect neurons in the brainstem and cerebellum involved in motor coordination and balance. Spinocerebellar ataxia type 1 (SCA1) Bcl-2 protein family is a CAG repeat disorder characterized by a selective degeneration of cerebellar Purkinje cells (PCs). PCs receive excitatory synaptic input from two cell types, cerebellar granule neurons and inferior olive (IO) neurons, whose climbing fibers (CFs) synapse on PC dendrites in the cerebellar molecular layer. It has recently been reported that CF input is reduced well before PC degeneration occurs in several mouse models of SCA1 (Barnes et al., 2011 and Duvick et al., 2010). Furthermore, using a conditional expression system, one study found that the effect of

the disease gene on CF input occurs during the first 5 postnatal weeks (Barnes et al., 2011). When disease gene expression was prevented during this early period, loss in CF input was partially reversed and PC degeneration was completely prevented (Barnes et al., 2011). Since expression of mutant ataxin-1 in this model is selectively restricted to PCs, the interaction between CF and PC neurons must be occurring in a bidirectional fashion. Thus, PCs expressing mutant protein prevent normal Electron transport chain synaptic structure and function of CFs, through an unknown signaling mechanism, and subsequent CF dysfunction early in the course of disease contributes to the eventual PC degeneration. Additional evidence for the importance of CF input to PC survival comes from the study of spinocerebellar ataxia type 7 (SCA7), another polyglutamine expansion disorder (Garden and La Spada, 2008). Both cerebellar PCs and IO neurons are among the selectively vulnerable populations in SCA7. When SCA7 was modeled in mice via transgenic expression of human mutant ataxin-7 protein, evidence for non-cell-autonomous degeneration of cerebellar PCs was noted early on. One group directed expression of the mutant gene specifically to PCs and did not observe significant pathology (Yvert et al., 2000).

First, a longer contralateral MD is necessary to induce an observable shift in ocular dominance (Sato and Stryker, 2010 and Sawtell et al., 2003). Even after 7 days of MD, the ocular dominance shift is less than that found in critical period mice with 4 day MD. Second, the shift in ocular dominance in adults induced by contralateral MD is predominantly an increase in open-eye responses with only a small and transient decrease in deprived-eye responses (Hofer

et al., 2006, Sato and Stryker, 2008 and Sawtell et al., 2003). Third, ipsilateral deprivation in adult mice produces no significant ODP (Sato and Stryker, 2008). Fourth, binocular deprivation in adult mice results in a substantial ocular dominance shift (Sato and Stryker, 2008). Fifth, adult ODP is less permanent than critical period ODP, with recovery after restoration Roxadustat cost of binocular vision taking half as long after long-term

MD (Prusky and Douglas, 2003). While ODP in young adult mice clearly differs from that in the critical period, the decline of plasticity in older adults suggests that plasticity mechanisms may continue to change later in life. Relatively little is known about the molecular mechanisms of adult ODP in the mouse and the extent to which they are similar to those that operate in the critical period. Some mechanisms, such as dependence on calcium signaling through NMDARs, are shared. Adult mice treated

with the competitive NMDAR antagonist, CPP, or mice lacking the obligatory NMDAR subunit, NR1, in cortex exhibited no adult ODP (Sato and Stryker, 2008 and Sawtell et al., selleck kinase inhibitor 2003). Other mechanisms of critical period ODP are not shared with adult ODP. For instance, adult TNFα-knockout mice that lack homeostatic scaling in vitro had normal increases in open-eye responses following MD while adult αCaMKII;T286A mice, which have a point mutation that prevents autophosphorylation of αCaMKII, lacked the strengthening of open-eye responses following MD (Ranson et al., 2012). Further evaluation of the shared and distinct molecular mechanisms between Dichloromethane dehalogenase critical period and adult ODP may reveal the factors that account for the decline in plasticity with age. The decline of ODP after the critical period may require “brakes” on plasticity mediated by specific molecular mechanisms to close the critical period and their continuous application to keep it closed (reviewed in Bavelier et al., 2010). There is evidence for several such mechanisms: persistently potent inhibition, neuromodulatory desensitization, and an increase in structural factors that inhibit neurite remodeling. Below we discuss some of the studies that have taken genetic and pharmacological approaches to interfere with these mechanisms in order to restore juvenile forms and levels of plasticity to adult V1.

The authors are supported by grants from Alberta Innovates Health Solutions (Polaris Award to B.L.M.), the Canadian Natural Sciences and Engineering Research Council to D.R.E and A.J.G., and the United States National Institute of Neurological Disorders and Stroke to B.L.M. and D.R.E. (NS020331-26). Thanks to click here Drs. Cyriel Pennartz, Jeremy

Seamans, Rob McDonald, Hendrik Steenland, and Rob Sutherland for helpful comments on the manuscript. “
“Complex movements are often described as the summation of simpler motor primitives. Typically, these modules have been defined in terms of overt movement kinematics, e.g., as patterns of force moving the limb to an equilibrium posture (Bizzi et al., 1991) or basic postural “synergies” composing hand movements (Mason et al., 2004; Santello et al., 1998).

At a more fundamental level, motor primitives have also been defined as synergistic contractions of muscles (d’Avella et al., 2003; Drew et al., 2008; Kargo and Nitz, 2003; Brochier et al., 2004; Torres-Oviedo and Ting, 2007). Electrical microstimulation studies have provided the most direct evidence that the nervous system encodes motor primitives. Whether applied intraspinally (Giszter et al., 1993; Aoyagi et al., 2004; Tresch and Bizzi, 1999; Zimmermann et al., 2011) or intracortically (Haiss and Schwarz, 2005; MDV3100 molecular weight Ramanathan et al., 2006; Stepniewska et al., 2005; Graziano et al., 2002), suprathreshold microstimulation lasting several

hundred milliseconds evokes complex multijoint forces that frequently drive the animal’s body toward invariant postures. These microstimulation studies have largely focused on overt movements rather than the underlying muscular control. Such kinematic studies have also concentrated on effectors with relatively few degrees of freedom. More complex convergent movements involving the macaque wrist Calpain and digits have been reported (Graziano et al., 2002, 2004a, 2005) but not yet quantified in a systematic manner. Moreover, while microstimulation is a valuable tool for causally probing neural function, it is unclear whether artificially elicited movements are a valid model of real behavior. In this study, we sought to address whether long-duration intracortical microstimulation (ICMS) would evoke naturalistic movements of the hand by recruiting muscles in a synergistic fashion. We electrically microstimulated sites throughout the motor cortex of two rhesus macaques, “G1” and “G2” (Figure 1A). The animals were awake during ICMS and were either moving their arms or at rest in different postures. We considered 46 locations (G1: 33, G2: 13), mostly in primary motor cortex (MI: 32 sites), plus others in premotor cortex, both dorsal (PMd: 9) and ventral (PMv: 5). We stimulated each site with biphasic pulses (2 × 0.2 ms) at suprathreshold currents (8–100 μA) and an intermediate frequency (200 Hz) over multiple (≥7), relatively long trains (150–500 ms).

The EC2 has a constant and a variable region, the latter contains several protein interaction sites (Berditchevski, 2001). All known tetraspanins contain the Cys-Cys-Gly sequence in the EC2, and >50% of tetraspanins buy Obeticholic Acid include a Pro-x-x-Cys-Cys sequence, that forms

disulfide bonds important for correct EC2 folding (Berditchevski, 2001). The N and C termini of individual tetraspanins are highly conserved across vertebrates, but differ markedly from one tetraspanin to the next; the C-terminal tail is especially divergent (Hemler, 2008). This suggests that, despite their short lengths, the N and C termini have specific functions, including linkage to cytoskeletal and signaling proteins. Tetraspanins regulate the signaling, trafficking and biosynthetic processing of associated proteins (Hemler, 2008), and may link the extracellular domain of α chain integrins with intracellular signaling molecules, including PI4K and PKC, both of which regulate cytoskeletal

architecture (Chavis and Westbrook, 2001, Hemler, 1998 and Yauch and Hemler, 2000). TM4SF2 transcripts are present in colon, muscle, heart, kidney, and spleen of mice, but are expressed most strongly in brain ( Hosokawa et al., 1999), primarily in neurons of frontal cortex, olfactory bulb, cerebellar cortex, caudoputamen, dentate gyrus, DAPT supplier and hippocampal CA3 ( Zemni why et al., 2000). Kainic acid treatment upregulates TM4SF2 mRNA, suggesting that TSPAN7 is involved in synaptic plasticity ( Boda et al., 2002). However, the function of TSPAN7 in the brain is unknown, and it is unclear how mutations affect neuronal development and function, and cause intellectual disability. To clarify TSPAN7′s

role in the brain, we examined its influence on the morphology and synaptic organization of developing hippocampal neurons. We focused on dendritic spines—main sites of excitatory synapses in the brain—because changes in spine morphology and density are associated with synaptic plasticity and learning (Kasai et al., 2010), and defects in spine morphology are associated with neurological disorders including intellectual disability (Humeau et al., 2009). We show that TSPAN7 promotes filopodia and dendritic spine formation in cultured hippocampal neurons, and is required for spine stability and normal synaptic transmission. We also identify PICK1 (protein interacting with C kinase 1) as a TSPAN7 partner. PICK1 is involved in the internalization and recycling of AMPA receptors (AMPARs) (Perez et al., 2001). Remarkably, TSPAN7 regulates the association of PICK1 with AMPARs, and controls AMPAR trafficking. These findings identify TSPAN7 as a key player in the morphological and functional maturation of glutamatergic synapses, and suggest how TSPAN7 mutations can give rise to intellectual disability.