This work extends our prior findings, which suggest that aggregat

This work extends our prior findings, which suggest that aggregate flux may occur in the setting of intracellular pathology, raising the possibility of therapies that can assist in aggregate clearance by targeting

extracellular mTOR activation species. This work has important implications for the design of therapeutic antibodies and suggests that targeting seeding activity in particular may produce the most effective agents. Several prior active and passive peripheral immunotherapy approaches against tau have also reduced tau pathology and improved behavioral deficits, but the underlying rationale for antibody choice was based either on a phospho-epitope, reactivity with neurofibrillary tangles, or was not stated (Asuni et al., 2007, Bi et al., 2011, Boimel et al., 2010, Boutajangout et al., 2010, Boutajangout et al., 2011, Chai et al., 2011 and Troquier et al., 2012). One tau immunization study, performed by vaccinating mice with full-length tau, induced pathology in wild-type mice (Rosenmann et al., 2006). However, subsequent active immunization approaches with phospho-tau peptides in tau transgenic models reduced tau pathology (Bi et al.,

2011 and Boimel et al., 2010) and showed behavioral improvement (Asuni et al., 2007, Boutajangout et al., 2010 and Troquier et al., INCB018424 2012). In a passive immunization study, JNPL3 tau transgenic mice were administered the PHF1 antibody intraperitoneally at 2–3 months of age, prior to the onset of tauopathy. PHF-1 targets a pathological form of abnormally phosphorylated tau (Otvos et al., 1994). Treatment reduced tau pathology and improved behavior (Boutajangout et al., 2011). However, while it decreased insoluble phosphorylated tau, next total insoluble tau

did not change. In another passive immunization study, JNPL3 and P301S mice (at age 2–3 months, prior to the onset of tauopathy) were peripherally administered the PHF1 or MC1 antibody, which targets an aggregate-associated epitope (Jicha et al., 1999). Both treatments improved tau pathology and delayed the onset of motor dysfunction (Chai et al., 2011). In these prior studies, the mechanism of action of the antibodies was not clear, and none was explicitly tested. Indeed, some proposed an intracellular mechanism (Sigurdsson, 2009). Moreover, no study appears to have produced the magnitude of reduction in tau pathology that we observed here, with the caveats that we infused antibodies into the CNS, while the other studies utilized peripheral infusion and different animal models were utilized. We designed this study explicitly to test a prediction that extracellular tau seeds are a key component of pathogenesis. We began with a selection process to pick antibodies capable of blocking tau seeding in vitro, purposely testing agents with a range of predicted activities.

Second, many amacrine cells—perhaps a majority of the total numbe

Second, many amacrine cells—perhaps a majority of the total number—perform find more some variety of vertical integration (the term is meant to contrast with lateral integration, as carried out by horizontal and wide-field amacrine cells). Only a small fraction of the 13 narrow field amacrine cell types found by MacNeil et al. (1999) were restricted to branching in narrow strata; the rest

communicate among several, sometimes all, of the layers of the IPL, like the cell shown in Figure 5. This means that they carry ON information into the OFF strata, and vice versa. This is termed crossover (for the crossing between ON and OFF layers) inhibition (because amacrine cells release GABA or glycine). It is the subject of very active investigation, which reveals a variety of interesting controls on the flow of information through the retina. The details are beyond the scope of this review, but an example is the finding

that some “excitatory” responses of ganglion cells to light are actually a release of amacrine mediated inhibition (Buldyrev et al., 2012; Demb and Singer, 2012; Farajian et al., 2011; Grimes et al., 2011; Molnar et al., 2009; buy JQ1 Nobles et al., 2012; Sivyer et al., 2010; Werblin, 2010). Third, most of the functions of amacrine cells are narrowly task-specific. An example is amacrine cell A17, a widely spreading neuron that places hundreds of electrotonically isolated synaptic boutons in contact with the output sites of the rod bipolar cell. At those points, the amacrine cell feeds back an inhibitory signal that improves the fidelity of information transmission by the rod bipolar

cell (Grimes et al., 2010; Sandell et al., 1989). This is the A17 cell’s primary, perhaps sole, task: and the A17 amacrine is in any case irrelevant to events that happen under daylight conditions. Another highly specialized amacrine cell, recently discovered in the ground squirrel retina, creates a specific receptive field property in a single type of ganglion cell (Chen and Li, 2012; Sher and DeVries, 2012). A blue-ON ganglion cell is well-known: it is excited by the blue-ON bipolar cell that selectively contacts blue cones. But electrophysiological recordings have encountered a blue-OFF ganglion cell, heptaminol inhibited when the stimulus lies at the short wavelength end of the spectrum. How can this happen if the only path through the retina is the blue-ON bipolar, carrying an excitatory signal? It turns out that a specific amacrine is driven directly by the blue-ON bipolar cell. The amacrine cell, like virtually all amacrine cells, is inhibitory to its postsynaptic partners. When excited by the blue-ON bipolar cell, this amacrine cell performs a sign inversion: it inhibits the ganglion cell upon which it synapses, thus creating a ganglion cell that is selective for blue stimuli and responds to a blue stimulus by slowing its firing—a blue-OFF ganglion cell. A final task-specific case is the role of the starburst amacrine cell.

To identify proteins that physically associate with PHF6, we used

To identify proteins that physically associate with PHF6, we used an approach of immunoprecipitation followed by mass spectrometry (IP/MS). We used a rigorous proteomics method that compares a specific IP/MS data set against a large set of unrelated parallel

IP/MS data sets, thus distinguishing high-confidence candidate interacting proteins (HCIPs) from background proteins (Behrends et al., 2010; Litterman et al., 2011; Sowa et al., 2009). Remarkably, AZD6738 concentration all four core components of the PAF1 transcription elongation complex, PAF1, LEO1, CDC73, and CTR9, were found as robust HCIPs of PHF6 (Figure 3A). We validated the interaction of HA-PHF6 and the endogenous PAF1 complex in coimmunoprecipitation analyses in cells (Figure 3B). Importantly, we also found that endogenous PHF6 associated with all four components of the endogenous PAF1 complex in mouse cerebral cortex at E17, coinciding temporally with migration of neurons to the superficial layers (Figure 3C). These data suggest that the PAF1 complex might represent a physiological interacting partner of PHF6. The PAF1 transcription elongation complex

was first identified in yeast as an RNA polymerase II-associated complex and plays a critical role this website in efficient transcriptional elongation along chromatin (Kim et al., 2010; Rondón et al., 2004; Shi et al., 1996). All four components of the complex were highly expressed during early development in primary cortical neurons and the cerebral cortex in vivo (Figure 3D). The role of the PAF1 complex in the brain has remained unexplored. We asked whether the PHF6-PAF1 interaction is functionally relevant in neuronal migration. We reasoned that if PHF6 acts via the PAF1 complex to regulate neuronal migration, loss of PAF1 would be predicted to disrupt neuronal migration. Consistent with this prediction, PAF1 knockdown by two distinct shRNAs substantially impaired neuronal migration in the cerebral cortex

in vivo, phenocopying the effect of PHF6 knockdown (Figures 3E, 3F, 3G, and 3H). Notably, knockdown of PAF1 led to downregulation of the other components of the PAF1 complex (Figure 3F) (Chen et al., 2009), suggesting that the intact PAF1 complex is required for proper neuronal migration. Collectively, these data suggest that PHF6 physically associates with the PAF1 Sodium butyrate complex and thereby drives neuronal migration. The finding that PHF6 interacts with the PAF1 transcription elongation complex and thereby promotes cortical neuronal migration led us to determine whether PHF6 exerts its function via regulation of gene expression. Because the PAF1 complex promotes transcription, we reasoned that PHF6 might stimulate the expression of genes that trigger neuronal migration. We performed microarray analyses of control and PHF6 knockdown primary cortical neurons. A large number of genes were downregulated in cortical neurons upon PHF6 knockdown (Table S1).

095) Further examination suggests that this

095). Further examination suggests that this selleck chemicals llc trend derives from differences among men and women in their chosen

running speed rather than an effect of speed per se. Running speeds (mean ± SD) for women and men were 2.98 ± 0.44 and 3.74 ± 0.59 m/s, respectively, and the difference was significant (p = 0.001, t test). As noted above, all but one woman used RFS while all but two men used MFS. Further, of the six adults with trials at both slow (<3.4 m/s) and fast (>3.4 m/s) speeds, none changed their foot strike usage at faster speeds. In fact, in all subjects with multiple recorded trials, none changed foot strike usage between trials. Thus, women were more likely to use RFS and to use a slower running speed than men. There is no evidence that subjects changed from RFS to MFS as speed increased. Results from bivariate comparisons were consistent with those of a multivariate nominal logistic regression. When speed, sex, and footwear (shod, barefoot) were used as independent variables predicting foot strike, only sex was a significant factor (p = 0.001). When adult and juvenile trials were pooled, both sex (p = 0.001) and age-class (p < 0.001) were significant predictors of foot strike usage, while speed (p = 0.157) and footwear (p = 0.101) were not. Foot, ankle, and knee angles at foot strike for

Hadza adults are Palbociclib concentration plotted against speed in Fig. 2. The effects of footwear, speed, and foot strike usage were entered into a multivariate nominal logistic regression to examine their effect on these angles. Not surprisingly, foot strike usage (RFS vs. MFS) was a significant predictor of foot angle at impact (p < 0.001), but speed (p = 0.54) and footwear (shod vs. unshod, p = 0.37) had no effect. Similarly, foot strike usage significantly predicted ankle angle at foot strike (p < 0.001), while neither speed (p = 0.21) nor footwear (p = 0.74) were significant factors. For knee angle, both foot strike (p = 0.006) and speed (p = 0.011) were significant factors, with more acute knee flexion at faster speeds, but footwear had no effect (p = 0.54). When juvenile trials are added to these comparisons, age-class does not significantly affect foot, ankle,

or knee angles (p > 0.05 all comparisons). Foot strike usage among Hadza adults was intermediate between that reported among the Kalenjin and Daasanach Megestrol Acetate populations (Table 1), and similar in some ways to the pattern reported for Tarahumara adults. When Hadza juveniles, adult men, and adult women are examined separately, some similarities with other populations emerge. Hadza men rarely use RFS (13.3% of subjects), similar to foot strike patterns of barefoot Kalenjin adolescents and Kalenjin adults who grew up barefoot, and to minimally-shod Tarahumara.6, 8 and 13 In contrast, Hadza women and juveniles often used RFS (90.9% and 85.7% of subjects, respectively), similar to Daasanach adults, habitually shod Kalenjin adolescents, and Tarahumara wearing conventional running shoes.

, Se

, FK228 order 2002). A targeted Rims1 mutation in the mouse leads to increased postsynaptic density and impaired associative learning as well as memory and cognition deficits ( Powell et al., 2004 and Schoch et al., 2002), and the frame shift allele

we found may lead to a similarly severe condition. Another intriguing candidate was the serine/threonine-specific protein kinase DYRK1A, which is located within the Down syndrome critical region of chromosome 21 and believed to underlie at least some of the pathogenesis of Down syndrome as a consequence of increased dosage. Several reports of likely inactivating mutations in DYRK1A result in symptoms including developmental delay, behavioral problems, impaired speech and mental retardation ( Møller et al., 2008 and van Bon et al., 2011), and a heterozygous knockout in the mouse also led to developmental this website delay and increased neuronal densities ( Fotaki et al., 2002). Truncating mutations in ZFYVE26 (encoding a zinc finger protein) are known to cause autosomal recessive spastic paraplegia-15,

consisting of lower limb spasticity, cognitive deterioration, axonal neuropathy and white matter abnormalities ( Hanein et al., 2008). It is possible that a heterozygous truncating mutation such as the de novo frame shift allele found in our study might cause a less severe version of this condition resulting in an ASD diagnosis. Other de novo mutations of interest were a 4 bp deletion in DST (encoding the basement membrane glycoprotein dystonin), which is associated with FMRP ( Darnell et al., 2011) and produces a neurodegeneration phenotype when inactivated in the mouse, and a nonsense mutation in ANK2 (an ankyrin protein involved in synaptic stability [ Koch et al., 2008]). A nonsense mutation in UNC80 has been linked next to control of “slow” neuronal excitability ( Lu et al., 2010). We also note that thirteen of the 59 LGD candidates appear to be involved in either transcription regulation or chromatin remodeling. Among the latter are three proteins involved in epigenetic

modification of histones: ASH1L, a histone H3/H4 methyltransferase that activates transcription (Gregory et al., 2007); KDM6B, a histone H3 demethylase implicated in multiple developmental processes (Swigut and Wysocka, 2007), and MLL5, a histone H3 methyltranserase involved in cell lineage determination (Fujiki et al., 2009). These three are also FMRP-associated genes. Fragile X syndrome (FXS) is one of the most common genetic causes of intellectual disability, with up to 90% of affected children exhibiting autistic symptoms. This has suggested overlaying recent understanding of FXS biology onto candidate ASD genes (Darnell et al., 2011). The FMR1 gene is expressed in neurons and controls the translation of many products.

, 1997, Lim et al , 1999 and Kasugai et al , 2010) The number of

, 1997, Lim et al., 1999 and Kasugai et al., 2010). The number of endogenous GABAAR complexes at synapses has been estimated to vary from 30 to as many as 200 (Nusser et al., 1997), and that of GlyRs from 10

to 70 (Singer and Berger, 1999 and Rigo et al., 2003). However, nothing is known about the absolute numbers of gephyrin molecules at inhibitory synapses or about the relative stoichiometry of receptors and scaffold proteins. Here, we make use of quantitative, dynamic, and three-dimensional (3D) nanoscopic imaging not only to determine the subsynaptic distribution of gephyrin and receptor complexes at inhibitory PSDs but also to count the number of gephyrin molecules 5-FU in vitro and receptor binding sites. With this project, our goal was to visualize inhibitory

synapses at superresolution and to extract detailed structural and quantitative information about the PSD. We carried out photoactivated localization microscopy (PALM) on rat dissociated spinal cord cultured neurons expressing photoconvertible constructs of the synaptic scaffold protein gephyrin (mEos2- or Dendra2-gephyrin). PALM was first conducted on fixed neurons as described in the Experimental Procedures section. The positions of single fluorophores were determined by Gaussian fitting of their point-spread function (PSF) and were corrected for lateral drifts using fiducial markers. The localization accuracy was estimated as the SD σ of multiple detections of the Selisistat mouse same fluorophore in subsequent image frames (Izeddin et al., 2011). The precision of localization heptaminol was marginally better for mEos2-gephyrin (σx = 11.2 ± 1.9 nm mean ± SD, σy = 11.9 ±

1.4 nm, n = 12 fluorophores) than for Dendra2-gephyrin (σx = 13.1 ± 2.1 nm, σy = 12.8 ± 2.0 nm, n = 11). When expressed in spinal cord neurons, mEos2-gephyrin and Dendra2-gephyrin accumulate in dense clusters that are visible by conventional fluorescence microscopy (Figure 1A). PALM imaging makes it possible to measure the sizes of these structures with high precision (spatial resolution, ∼25–30 nm). Image segmentation of the rendered PALM images indicates an apparent surface ranging from 0.01 to 0.1 μm2 (Figure 1B). The PALM experiments also revealed the presence of an additional population of gephyrin clusters below 0.01 μm2 that is not visible in the diffraction-limited images (Figures 1A and 1B). To determine the subcellular localization of both types of clusters, we combined PALM imaging with direct stochastic optical reconstruction microscopy (dSTORM) as described elsewhere (Izeddin et al., 2011). In these experiments, the presynaptic protein bassoon was labeled with Alexa 647-tagged antibodies. Dual-color PALM/STORM images show the apposition of the large gephyrin clusters with bassoon-positive structures, identifying them as inhibitory PSDs (Figure 1C).

“Children and youth receive numerous physical health benef

“Children and youth receive numerous physical health benefits from physical activity (PA), including improved fitness, cardiovascular function, metabolic function, and bone health.1 Despite these health benefits, many children continually fail to meet PA recommendations.2 To increase PA in a large number of children, experts have targeted schools as a setting in which to promote PA.3 and 4 Most efforts to sell PA to school administrators and policymakers have emphasized its health benefits, with little success. Therefore, advocates have searched

for an alternative approach to persuade decision selleck products makers to include PA in the school day. One approach has been to associate PA with academic achievement. Because the primary goal of schools is student

academic achievement, the key to increasing PA in schools would be to show that PA improves academics. Academic outcomes have become even more important since 2001, when the No Child CH5424802 mouse Left Behind legislation raised the stakes of standardized academic achievement tests in the United States. As administrators have increased the focus on academic achievement since then, schools increasingly have eliminated PA opportunities.5 In response, public health researchers have searched for the “holy grail” of PA in schools: a positive connection between PA and academic achievement. If scientific evidence verifies and supports a positive connection between PA and academics, administrators may be more through likely to increase PA opportunities during the school day. Researchers have been studying PA and academic achievement for over half a century. Now, many researchers contend that sufficient evidence exists to institute school PA policies that will improve (or at least not detract from) academic achievement. If this conclusion is promoted before definitive data are available, however, negative consequences may result. If

researchers promote PA as a way to improve academics, and administrators later fail to see this association, promotion of PA in schools could fall several steps backwards. Government agencies have conducted reviews on PA and academic achievement that have potential policy implications. The Centers for Disease Control and Prevention (CDC) reviewed the literature through 2008 on PA during the school day and academic achievement.6 The CDC review concluded that PA may have a positive effect or no effect on academic performance. Additionally, the PA Guidelines Advisory Committee reviewed literature through 2007 on the health benefits of PA for children and youth, including the mental health benefits.1 In its report, the Committee concluded, “Although observational studies have found relationships between physical fitness and grades and test scores, those between PA and direct measures of academic achievement often have had null findings.

Secondly, residing in an area with high levels of maternal educat

Secondly, residing in an area with high levels of maternal education or belonging to a migrant family was associated with an increase in immunization rates in bivariate analyses. These effects disappeared in multivariable analyses, reflecting possible confounding by travel time to vaccine clinics. Overall, however, the effect of maternal education produced higher coverage with three doses of pentavalent vaccine at age 12 months in the most educated areas compared to the less educated ones. This result is consistent with 2008 Kenya

DHS data showing substantially higher coverage for all vaccines in children with educated mothers compared to those with uneducated mothers (unpublished data, AZD9291 Kenya 2008 DHS), and buttresses the notion of a strong relationship between maternal education and child health. Geographic access to care in the Kilfi Epi-DSS is comparable to most other learn more regions of Kenya [31] and immunization coverage is similarly high based on data from the most recent Demographic and Health Survey and WHO/UNICEF joint coverage estimates. It is therefore likely that

the vast majority of Kenyan children enjoy as equitable and timely access to immunization as do residents of our study area. In this context, the introduction of a new, effective vaccine against pneumococcal disease is likely to reach all children at an early age and lead to substantial improvements in child health. The authors wish to thank the Immunization Coverage Survey field team including Francis Kanyetta, Joseph Kenga and Christopher Nyundo, as well as Li Xingyu for help with project management. The Kilifi Epi-DSS is part of the INDEPTH network of demographic surveillance sites. This study is published with the permission of the director of the Kenya Medical Research Institute (KEMRI), Nairobi. “
“The author’s wish to apologise that one reference was incorrectly represented in the original paper. The incorrect reference is: [15] Tangcharoensathien V, Limwattananon S, Chaugwon

R. CYTH4 Research for Development of an Optimal Strategy for Prevention and Control of Cervical Cancer in Thailand. Research report submitted the World Bank. Nonthaburi: Ministry of Public Health, Thailand, 2008. “
“Pneumoviruses are an important cause of respiratory infections in mammals [1]. One well-known member of the pneumovirus genus is hRSV, a major cause of severe respiratory disease in infants and elderly [2]. A failed vaccine trial using formalin-inactivated hRSV (FI-RSV) in the 1960s that led to enhanced disease instead of immune protection [3], [4], [5] and [6], has triggered intense efforts to elucidate how to induce immune responses that can prevent or protect against natural hRSV infection without causing pathology.

, 2007) In parallel, it is noteworthy that the outcome of resear

, 2007). In parallel, it is noteworthy that the outcome of research on brain and cognitive mechanisms of memory spills into key aspects of daily life and society (Schacter and Loftus, 2013). The growth of “social neuroscience” portends growing interest in social aspects of memory BMS-777607 research buy in both human and animal-based neuroscience. Similarly, it seems

that more attention is devoted to the effectiveness of realistic milieu in animal models used in memory research, with renewed emphasis on the real-life cognitive universe of rodents (particularly space, odors, somatosensory stimuli, and their interactions, e.g., Morris et al., 2006, Sauvage et al., 2008 and Buzsáki and Moser, 2013). The general understanding, itself rooted in several older animal psychology schools and now resurrected, is that animals learn better when the memoranda make sense in their world. Hints of a similar trend seem to emerge in the primate literature as well (Paxton et al., 2010). It is likely that widespread use of novel consumer technology (such as Google-type

glasses or personal activity monitors), miniaturization of noninvasive functional imaging devices for humans, and facilitated real-time web communication will render more realistic memory experiments easier and more popular. The dominant taxonomy of memory systems, echoing earlier philosophical notions (Ryle, 1949), was shaped by studies of “global amnesics” like H.M. and other patients (Scoville and Milner, 1957, Rosenbaum et al., 2005 and Squire and Wixted, 2011), supported by lesion studies in animal models (Mishkin,

1982, Olton DAPT molecular weight et al., 1979 and Fanselow, 2010). It has long portrayed the brain as possessing two major types of memory systems—declarative (explicit) memory for facts and events, for people, places, and objects (“knowing that”) and nondeclarative (implicit) memory, the memory for perceptual and motor skills (“knowing how”). Whereas declarative memory is held to involve particular types of representation and conscious awareness for recollection, it also requires an intact hippocampus—at least at the time that a memory is acquired. In contrast, nondeclarative memory is thought Rolziracetam to be a heterogeneous collection of experience-dependent changes shown in behavior and not to rely on the hippocampus but on a number of other brain systems: the cerebellum, the striatum, the amygdala, and, particularly in invertebrates, simple reflex pathways themselves. This taxonomy was immensely useful as a conceptual framework for both human and animal studies, in teaching where it is little short of a blessing, and as an engine for new experimental programs. Recent ideas and data, however, have raised questions about this taxonomy. One issue relates to what can be concluded from brain damage/lesion studies, which identify necessity, compared to physiological approaches, which measure correlates of a presumed process—be it in neural firing, BOLD, IEG activation, or in other ways.

In this study, we describe a remarkable correlation between the P

In this study, we describe a remarkable correlation between the PD of directionally tuned neurons and their laminar arborization profile in the optic tectum of larval zebrafish. In the tectum, different cell morphologies have been linked to genetic signatures for some cell types (Scott and Baier, 2009; Robles et al., 2011). On the other hand, recent measurements of directional tuning have found DS neurons within a global tectal cell population but without genetic or morphological discrimination (Niell Obeticholic Acid ic50 and Smith, 2005; Ramdya and Engert, 2008; Sumbre et al., 2008). Here, we provide evidence that DS neurons with

different PDs arborize in distinct layers in the superficial, retinorecipient layers of the neuropil. Furthermore, we isolated transgenic lines that express GFP or GCaMP3 in these cell types of opposite directional tuning. selleck chemicals Excitatory synaptic inputs were directionally tuned and matched the PD of spike output in these cells, while inhibitory inputs were often tuned to nonpreferred directions. In conclusion, the correspondence between structure and function of tectal DS neurons suggests that higher stimulus features could be processed and transmitted within specialized sublayers in the tectal neuropil. This indicates that the central principle of laminar-specific

feature extraction may also apply to visual centers beyond the vertebrate retina (Roska and Werblin, 2001; Wässle, 2004). We found two morphologically distinct DS cell types with opposite PDs. One class (“type 1”), selective for RC motion components, was bistratified, with a distal dendritic arborization tightly restricted to a band within the SFGS/SO border region and a smaller arborization between the SFGS and SGC. The morphology of this type resembled that of a bistratified periventricular interneuron type (bs-PVIN), which is selectively targeted using a dlx5/6 enhancer element ( Robles et al., 2011). Those bs-PVINs were found to be negative for GABA immunoreactivity,

unlike the the bistratified type 1 neurons in our study. This raises the possibility that morphologically similar cell types in the tectum could differ in transmitter phenotype, which could be the result of homeostatic or activity-dependent transmitter specification ( Spitzer, 2012). Another cell class (“type 2”) was CR-DS and had a dendritic/axonal tree that was less confined to a narrow band but ramified to a greater extent in the middle and superficial sublaminae of the SFGS (SFGSB,D). Furthermore, it showed a second band of neurites at the border between the SFGS and the SGC. Somata of this cell type did not colocalize with vglut2a:DsRed fluorescence and were positive for GAD65/67, suggesting that they were GABAergic as well. During random selection of neurons for patch-clamp analysis, we also observed a cell type that showed preference for stimuli with UD components, whose dendritic/axonal branches were mostly located in the deeper layers of the SGC.