365699-S, Hs.506230-S, GI_41149683-S, Hs.208111-S, GI_41149726-S, hmm21473-S, Table S1) for ESTs from GenBank in the same genomic window. Data of four ESTs were excluded from the analysis, because their probes did not map completely or uniquely to any target EST sequence of the current GenBank database (GI_37541937-S, hmm21470-S, GI_37541941-S, hmm21472-S). Target sequences of all probes included in expression analyses mapped uniquely and completely to the human genome and are all devoid of known common variations denominated by dbSNP build 129.

Structural MRI with high-resolution T1-weighted images adequate for morphometry was available for 204 patients with recurrent unipolar depression and 186 control subjects. MRI was acquired at the MPI of Psychiatry in the context of the acquisition Dorsomorphin of the Munich recurrent buy I-BET151 unipolar depression replication samples. A detailed description of study participant selection and image processing is available in the Supplemental Experimental Procedures. In brief, image preprocessing was performed as for voxel-based morphometry to gain gray matter (GM) maps with preserved local volume in stereotactic space. Histologically

validated cytoarchitectonic probability maps (Amunts et al., 2005) were used to create regional volumetry masks for the left and right hippocampus and subregions cornu ammonis (CA: CA1–3), subiculum (SUB), and dentate gyrus (DG). The sum of all modulated GM voxels within the regional masks was calculated using in-house software programmed in IDL (http://www.creaso.com). Analysis of covariance (ANCOVA) was performed for left and right total hippocampal GM volume and each three subregions with two-level factors group (patients, controls), genotype (rs1545843 AA versus AG/GG, equally for rs1081681), and gender, covarying for age, squared age, total GM volume, and sequence type. Levene’s tests for equality of error variances was explored and found nonsignificant for all tests (Figure S4). p values were compared with a Bonferroni-corrected threshold to adjust

for 18 tests (two SNPs, nine volumetric measurements [including motor cortex as control region]: Thalidomide 0.05/18 = 0.0028). Both nominal and corrected p values are indicated in Figure 5 and Table S2. These are discussed in the Supplemental Experimental Procedures. Male CD1 mice were used for all experiments. Animals were 28 days old at the day of arrival and were kept on a 12L:12D cycle. Food and water was provided ad libitum. The experiments were carried out in accordance with European Communities Council Directive 86/609/EEC. All efforts were made to minimize animal suffering during the experiments. The protocols were approved by the committee for the Care and Use of Laboratory Animals of the Government of Upper Bavaria, Germany. The chronic social stress procedure was performed as described previously (Schmidt et al., 2007 and Sterlemann et al., 2008) (see Figure S5 and Supplemental Experimental Procedures).

The latter step is a concentration gradient-driven process, check details influenced by the drug molecular characteristics and impeded by diffusional resistances of the microchannels and the tissues beneath [20] and [25]. In a recent study, we reported on the effect of MN array characteristics and application variables on the

in vitro transdermal delivery of Rh B encapsulated in PLGA NPs across full thickness MN-treated porcine skin [10]. In the present work, we aimed at providing more knowledge on the contribution of characteristics of nanocarrier and encapsulated dye to MN-mediated transdermal delivery of nanoencapsulated Apoptosis inhibitor dyes. The skin model used was full thickness porcine ear skin (approximately 1164 μm-thick), a well-established model representing full skin resistance and possessing characteristics similar to those of human skin [35]. Rh B or FITC-loaded NPs prepared at a relatively high emulsion homogenization speed (15,000 rpm)

with 1% w/v DMAB were generally monodisperse with PDI < 0.2 and positively charged due to adsorption of the cationic surfactant. Zeta potential values exceeded 30 mV (36.1–67.6, Table 1), indicating physical stability [36]. This was obvious in TEM images of sample NPs (Fig. 3). FITC NPs prepared with PVA as emulsion stabilizer were negatively charged (−4.5 mV, Table 1). Reduction in the particle size of 20% w/w Rh B-loaded PLGA 50:50 NPs (F1–F3) in the range 422.3–155.2 nm (Table 1) resulted in a significant increase in permeation of Rh B across MN-treated skin (Fig. 4). For instance, a 2.7-fold reduction in the mean diameter of F3 compared to F1 NPs led to a fivefold increase in Q48. It has been demonstrated that permeation characteristics of a NP through microchannels were significantly affected by NPs size relative to the pore size [37]. As the width

of MN-created microchannels is usually in the micron range [23], that is, significantly larger than the size range of test NPs in the present study, and NPs size dependence of Rh B skin permeation can be explained by faster release of the encapsulated however water soluble Rh B from smaller size NPs with larger surface to volume ratio. Particle size is a factor known to affect drug release from polymeric NPs [38]. Further, translocation of PLGA NPs across full thickness human abdominal skin was shown to be NPs size dependent, despite the larger microchannel size [22] and [23]. Combined findings suggest deeper and more extensive influx of smaller NPs through MN-created channels leading to enhanced transdermal delivery of the water soluble dye released at the deeper NPs deposition sites.

, 1996, Tran et al., 2007 and Yazdani and Terman, 2006). Previous work has shown that Sema5A and Sema5B can act as guidance cues to either attract or repel processes belonging to different neuronal populations (Goldberg et al., 2004, Hilario et al., 2009, Kantor et al., 2004, Lett et al., 2009 and Oster et al., 2003). We generated mice harboring knockout alleles

of Sema5A and Sema5B by targeting exon 6 of Sema5A and exon 2 of Sema5B, each of which encode the first 41 or 51 amino acids, respectively, of these proteins (see Figure S1 available BTK inhibitor online). Our Sema5A and Sema5B mutant mice lack full-length Sema5A and Sema5B proteins ( Figures S1G and S1H). Unlike the early embryonic lethality observed in previously generated Sema5A null mice (in a mixed 129/NMRI genetic JAK2 inhibitor drug background) ( Fiore et al., 2005), we found that in a 129/C57BL/6 mixed genetic background, our Sema5A−/−, Sema5B−/−, and Sema5A−/−; Sema5B−/− mice are viable and fertile. This difference could be due to either the utilization of different targeting strategies and/or mouse genetic backgrounds. These results strongly suggest that our Sema5A and Sema5B mutant mice are null

mutants. Sema5A−/−; Sema5B−/− mice exhibit severe defects in the stereotypic neurite arborization of multiple amacrine cell types. In Sema5A−/−; Sema5B−/− mice, tyrosine hydroxylase (TH)-expressing dopaminergic amacrine cells, which predominantly stratify within the S1 sublamina of the IPL in wild-type (WT) retinas ( Figure 1I), exhibit dramatic mistargeting within both the INL and OPL ( Figure 1L). Similarly, vGlut3-expressing amacrine cells, which mostly stratify within the S2/S3 sublaminae medroxyprogesterone of the IPL in WT retinas ( Figure 1M), show severe neurite mistargeting within both the IPL and INL in Sema5A−/−; Sema5B−/− mice ( Figure 1P). In addition, AII amacrine cells (labeled with Disabled-1 [Dab-1]), cholinergic amacrine cells (labeled with choline acetyltransferase [ChAT]), calretinin-positive cells, and calbindin-positive cells all exhibit

pronounced ectopic neurite extension toward the outer retina in these mutant mice ( Figures 2A–2H). Importantly, these defects are observed with full penetrance and expressivity in Sema5A−/−; Sema5B−/− animals (n = 12 Sema5A−/−; Sema5B−/− mice; n = 12 WT mice). Sema5B−/− mice also exhibit neurite arborization defects involving these same neuronal subtypes ( Figures 1K and 1O; data not shown), although these phenotypes are less severe than those seen in Sema5A−/−; Sema5B−/− mice. Sema5A−/− mice, and also Sema5A+/−; Sema5B+/− mice, did not show defects in these same classes of retinal neurons ( Figures 1J and 1N and Figure S2; data not shown). These results suggest that Sema5A and Sema5B play redundant roles in regulating multiple amacrine cell neurite arborization events in vivo.

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

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

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

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

My aims here are to see how close we have come to a complete census, to review the principles by which the diverse cell types are organized, to illustrate some of the ways in which they create the retina’s abilities, and to forecast the path by which we may progress. I will begin by outlining three large rules that govern relations among the retina’s neurons. The retina’s processing of information begins with the sampling of the mosaic of rod and cone photoreceptors

by the bipolar and horizontal cells. The photoreceptors form a single CP-868596 mw sheet of regularly spaced cells. Rod photoreceptors, specialized for vision in dim light, outnumber cone photoreceptors by about 20-fold in all but a few mammalian retinas. All rods contain the same light-sensitive pigment, rhodopsin. With one known exception (so far), each cone contains one—and only one—of several cone opsins, each with a different spectral absorption; as will

be discussed later, these are the basis of color vision. Both rods and cones respond to light by hyperpolarizing. Rods and the chromatic classes of cones can be easily identified in intact retinas by morphology and by their expression of the different opsins. This review will pass lightly over the rod system, which molecular dating shows to have MEK activation been a late evolutionary addition to the retina’s tool kit. This is not to say that rods are unimportant, nor that they are uninteresting. Yet the retinal circuitry truly dedicated to rod function includes only four cell types: the rod itself, a bipolar cell that receives input only from rods (“rod bipolar cell”), an amacrine cell that modulates the bipolar

cell’s output, no and an amacrine cell that feeds the output of the rod system into the circuitry that processes information derived from cones. A second pathway from rods to ganglion cells exists in some animals (it involves gap junctions with cones), but in either case the strategy is the same: the late-evolving rods inject their signals into circuitry that had already developed to service the cones (Famiglietti and Kolb, 1975; Nelson, 1982; Nelson and Kolb, 1985; Sandell et al., 1989; Strettoi et al., 1990, 1994; Strettoi et al., 1992). The types of cones are structurally and, as far as is known, functionally similar. (This review pertains primarily to mammalian retinas.) Their functional types are defined by the opsin that each type expresses. A generic mammal expresses one short wavelength-sensitive cone and one long wavelength. Comparison of the two outputs forms the basis of most color vision. The numbers of rods and cones are known with great precision. They have been counted and their topography mapped for dozens of mammalian and nonmammalian species. These have been collected at http://www.retinalmaps.com.au (Collin, 2008). For humans and the common laboratory animals, the accounting of photoreceptor cells is complete.

, 2007). In a recent study using fMRI, it was shown that the gains in motor skills related to music-supported therapy in stroke patients are related to increased functional auditory-motor connectivity after therapy (Rodriguez-Fornells et al., 2012). The auditory-motor interactions that are specific to music (Zatorre et al., 2007), and the increased potential for plasticity in multimodal training paradigms (Lappe et al., 2008), might thus underlie the improvements seen in these music-based rehabilitation approaches. Additionally, it can be assumed that other aspects of the music treatments such as enjoyment of the therapy sessions, increased Selleckchem Nintedanib motivation

and reward, and social

aspects of the interaction during singing and music making contribute to the efficacy of the training approaches. More recently, music-based therapy has also been successfully applied for tinnitus, a neurological condition that seemed untreatable for a long time. Research showing that the typical ringing noise selleckchem that is perceived by tinnitus patients can be based on mal-adaptive cortical plasticity after deafferentation of cortical auditory neurons (Eggermont, 2007) on the one hand and research showing short-term plasticity of the tuning of auditory neurons after band-passed noise on the other hand (Pantev et al., 1999) inspired a treatment approach aimed at reversing such maladaptive cortical plasticity (Okamoto et al., 2010). Listening to self-selected music that was notch-filtered to exclude the individual tinnitus frequency over 6 months significantly reduced perceived tinnitus loudness and annoyance as well as evoked auditory potentials to the tinnitus frequency, compared to a placebo control group. Based on findings from the animal literature (Eggermont, 2007), the treatment Resminostat is assumed to take advantage of the lateral inhibition that occurs on the level of auditory cortex, and that counteracts

the maladaptive reorganization that lead to the tinnitus percept in the first place. This shows that not only active music making, but also massed passive listening can lead to clinically relevant reorganization in the brain. Training-related plasticity in the human brain has been studied in a wide variety of experimental approaches and paradigms, such as juggling, computer games, golfing, and other training activities (e.g., Bezzola et al., 2011; Boyke et al., 2008; Draganski et al., 2004). We hope to have convinced the reader that musical training is a useful experimental framework that offers the possibility to compare studies using similar training activities, which facilitates the integration of findings across studies and modalities.

, 2009 and Royer et al., 2010). In contrast, LFP θ in ventral hippocampus would have been an unsuitable reference. LFP θ phase in ventral hippocampus varies dramatically between recordings, preventing a reliable comparison of phase locking http://www.selleckchem.com/products/epacadostat-incb024360.html between animals (Hartwich et al., 2009; Table S6). Moreover, ventral hippocampal θ oscillations have low amplitude and occur only transiently (Adhikari et al., 2010, Hartwich et al., 2009 and Royer et al., 2010), compromising the isolation of θ epochs using unbiased methods

(Csicsvari et al., 1999 and Klausberger et al., 2003) and the calculation of θ phases. To validate that dCA1 signal predicted spike timing of BLA neurons relative to ventral hippocampal θ, we performed C646 experiments that included a vCA1-subiculum electrode (n = 3 animals, 6 neurons). Ventral stratum radiatum LFP signal was used as second reference. Theta oscillations were intermittent and had generally low amplitude, as reported in behaving rodents (Figure S9; Adhikari

et al., 2010 and Royer et al., 2010). As expected, dCA1 signal predicted BLA unit firing modulation with ventral hippocampal θ. Differences between the phases of dCA1 and vCA1-subiculum LFP θ oscillations were similar to, and correlated with the difference between the preferred phases of neuron firing calculated with the two references (Pearson’s correlation r = 0.975, p = 0.025 and circular-circular correlation: Fisher and Lee’s method, Oriana software, p < 0.05, n = 4: 3 principal cells, 1 PV+ basket cell; Figures 7 and S9). Moreover, θ modulation strengths of units calculated with dorsal and ventral hippocampal

references were similar and linearly correlated (Pearson’s correlation r = 0.976, p = 0.024; n = 4; Figure 7D). These results establish that dCA1 is a suitable and sensitive reference to study the coupling of BLA neuron firing to hippocampal θ. This study defines several types of BLA interneurons and their role in shaping BLA activity in relation to dCA1 θ oscillations and noxious stimuli, two for processes critical in forming emotional memories. The key findings are the following: dendrite-targeting CB+ interneurons provide inhibition to BLA principal cells in phase with hippocampal θ oscillations. The firing of PV+ basket cells is not tightly synchronized with θ oscillations. Axo-axonic cells consistently and dramatically increase their firing in response to noxious stimuli. In addition, we discovered a GABAergic cell type well placed to coordinate spontaneous and sensory-related BLA-AStria interactions. Our results support the hypothesis that interneurons are critical in regulating timing in the BLA, and that they operate in a cell-type-specific manner. We demonstrate that this principle is not limited to firing relationships with ongoing oscillations, but also applies to the integration of sensory information.

This Df screen had two problems. First, homozygotes for many Dfs in the kit had severe CNS defects that preclude screening. To alleviate this, we replaced Dfs for which development failed with smaller Dfs that allow better development, creating a “phenotype Df kit” with which >80% of the genome can be screened for ligands (http://fly.bio.indiana.edu/Browse/df/zinn.php). This kit can also be used for systematic genome screening for any embryonic phenotype, and such a screen requires analysis VE-822 order of less than 400 lines (Wright

et al., 2010). Second, if multiple RPTP ligands are expressed in overlapping patterns, deletion of a gene encoding one ligand might not produce a decrease in staining that can be unambiguously scored. For Lar-AP, deletion of Sdc only slightly reduces axonal staining. A Lar-AP mutant that cannot bind

to HSPGs stained CNS axons with equal intensity in wild-type and Sdc embryos, indicating that Lar has non-HSPG axonal binding partners ( Fox and Zinn, 2005). In this paper, we describe a screen that addresses the second problem. GAL4-dependent expression of Sdc on muscles conferred bright staining with Lar-AP (Fox and Zinn, 2005). This suggested that if we ectopically expressed many cell-surface and secreted (CSS) proteins, potential ligands could be identified by ectopic staining with RPTP-AP probes. We had assembled a collection of lines bearing P element insertions with GAL4 binding sites upstream of 410 CSS protein genes in order to screen for genes involved in targeting of motor axons to muscle fibers (Kurusu et al., 2008). These lines were later used to find genes affecting axonal and dendritic targeting

Sirolimus in the antennal lobe (Hong et al., 2009, 2012). Screening the CSS insertion lines for ectopic staining with Ptp10D-AP (10D-AP) identified a binding partner for Ptp10D, Stranded at second (Sas). The sas gene encodes two large cell-surface proteins of unknown function that are expressed on the apical surfaces of epithelially derived cells ( Schonbaum et al., 1992). Ptp10D is a type III RPTP. It is orthologous to a group of four mammalian RPTPs that negatively regulate receptor TKs (RTKs) by direct dephosphorylation (reviewed by Matozaki et al., 2010). PTPRJ (DEP-1/CD148), which corresponds to the Suppressor of colon cancer 1 (Scc1) gene ( Ruivenkamp et al., 2002) dephosphorylates Methisazone the epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and CSF1R/Met growth factor RTKs ( Chabot et al., 2009; Palka et al., 2003; Tarcic et al., 2009). PTPRB (VE-PTP) regulates Tie-2 ( Winderlich et al., 2009), and PTPRO regulates TrkC and Eph RTKs ( Hower et al., 2009; Shintani et al., 2006). Type III RPTPs can be tyrosine-phosphorylated on a C-terminal YxNΦ (Φ = hydrophobic) motif, and this causes activation of Src-family tyrosine kinases (SFKs) ( Murata et al., 2010). Ptp10D is expressed on CNS axons (Tian et al., 1991; Yang et al.

In a similar situation, we previously showed that FMRP deficiency in mice leads to impaired hippocampal neurogenesis and hippocampal-dependent learning and that FMRP regulates DG-NPCs via

NVP-BKM120 in vitro the Wnt signaling pathway ( Guo et al., 2011 and Luo et al., 2010). However, in the current study, we discovered that DG-NPCs in Fxr2 KO mice have increased neuronal differentiation with no change in Wnt signaling in Fxr2 KO DG-NPCs. In addition, FMRP inhibits Gsk3β protein expression by repressing translation without affecting Gsk3β mRNA stability, whereas FXR2 represses Noggin protein expression by reducing the stability of Noggin mRNA. Furthermore, FMRP deficiency results in increased proliferation of both stem cells and transient amplifying cells in the adult DG ( Luo et al., 2010), and loss of FXR2 only affects stem cell proliferation in the DG. Therefore, both FMRP and FXR2 can regulate adult hippocampal NPCs by binding to the mRNAs of NPC regulators, but their mechanisms, as

well as their functional outputs, are different. Posttranscriptional regulation of critical regulatory mRNAs by RNA-binding proteins is likely to be a common mechanism during critical cellular processes ( Bhattacharyya IWR-1 cost et al., 2008, Callan et al., 2010, Tervonen et al., 2009 and Yang et al., 2009), but evidence for this in adult mammalian neurogenesis is rather limited. Our data are among the first to demonstrate that RNA-binding proteins can play important roles in the differential regulation of NPCs residing in different adult brain regions. Future studies examining the role of FXR2 in generating the inhibitory interneurons of the olfactory bulb and excitatory neurons of the DG, particularly in comparison with FMRP, will further contribute to our knowledge of these important RNA-binding proteins in adult neurogenesis and plasticity. All animal procedures were performed according to protocols approved by the University of

New Mexico Animal Care and Use Committee. The Fxr2 KO mouse strain on the C57B/L6 genetic background published previously ( Bontekoe et al., 2002) was obtained from the Emory University fragile X consortium. The NogginLacZ first transgenic mice were maintained and genotyped as described previously ( Stottmann et al., 2001). In vivo neurogenesis analyses were performed essentially as we have previously described (Guo et al., 2011, Luo et al., 2010, Smrt et al., 2007 and Zhao et al., 2003). Mice were given four injections of BrdU (50 mg/kg) within 12 hr to label all dividing cells in adult germinal zones within this time period based on a published paradigm (Hayes and Nowakowski, 2002). Mice were then euthanized either at either 12 hr or one week following the final BrdU injection. Antibody information is provided in Supplemental Experimental Procedures. Quantification of BrdU+ cells in the DG and SVZ and phenotypic analysis of BrdU+ cells were performed as described previously.

, 2011, Kim et al., 2011, Squire and Wixted, 2011, Squire and GABA pathway Zola-Morgan, 1991 and Suzuki, 2009), in spite of recent reports suggesting that perception may also be compromised (Barense et al., 2007, Barense et al., 2010b, Barense et al., 2011b, Bartko et al., 2007, Baxter, 2009, Buckley et al., 2001, Lee et al., 2005a, Lee et al.,

2005b and Lee and Rudebeck, 2010). A recent representational-hierarchical account unites these findings, suggesting that apparently distinct mnemonic and perceptual functions may arise from common representations and computational mechanisms. The representational-hierarchical account proposes that the perirhinal cortex (PRC) can be considered an extension of the representational hierarchy within the ventral visual stream (VVS) (Barense et al., 2005, Bussey and Saksida, 2002, Bussey et al., 2002, Desimone and Ungerleider,

1989, Graham et al., 2010 and Riesenhuber and Poggio, 1999). It is well-established that as information flows from posterior to anterior regions of the VVS, representations of visual stimulus features are organized hierarchically in increasingly complex conjunctions (Figure 1; Desimone and Ungerleider, 1989, Riesenhuber and Poggio, 1999 and Tanaka, 1996). When an object is viewed, multiple representations of this object are activated throughout the entire VVS, with different representations occurring at different stages of the pathway. The object’s low-level features are represented in early posterior regions, whereas conjunctions of features Linifanib (ABT-869) are represented in more anterior regions, Dasatinib with the most complex feature conjunctions—perhaps at the level of the whole object—being represented in regions such as the PRC. The traditional memory systems view argues that MTL structures such as PRC support exclusively mnemonic functions (Clark et al., 2011, Kim et al., 2011, Squire and Wixted, 2011, Squire and Zola-Morgan, 1991 and Suzuki, 2009). In contrast, the representational-hierarchical view proposes that stimulus representations throughout the VVS and MTL are useful for any cognitive

function that requires them (Bussey and Saksida, 2002, Cowell et al., 2006 and Cowell et al., 2010a). This account seeks to explore whether damage to the high-level representations maintained in MTL regions can account for a variety of deficits observed in amnesia. Under this model, one need not postulate separate memory and perceptual systems. One important prediction of this view—yet to be tested in humans—is that if the complex, object-level representations within the PRC are damaged, interference from incidental, irrelevant features can become catastrophic (Cowell et al., 2006 and McTighe et al., 2010). A stream of visual input (such as that encountered over a delay) can create interference at the level of individual features, simply because different objects tend to share lower-level features (e.g.