, 2000 and Fukuoka et al., 2001). In line with all this evidence, anti-inflammatory drugs such as steroids are effective in reducing pain in many circumstances, especially when applied locally (Wong et al., 2010). However, their adverse side effects such as weight gain, high blood pressure, and increased risk of osteoporosis or diabetes render them unsuitable for long-term analgesic therapy. Alternative strategies which modulate the inflammatory response, and particularly the proalgesic components,

would therefore be of considerable potential benefit selleck chemicals in the treatment of chronic pain. A second locus for amplification of pain-related signals occurs within the central nervous system, a process called central sensitization by analogy with its peripheral counterpart. Gemcitabine datasheet The best studied forms are in the spinal cord, where

projection neurons that carry sensory information to the brain become more responsive to both noxious and innocuous inputs. Central sensitization is a form of synaptic plasticity and is precipitated by repetitive activity in nociceptors and depends critically on recruitment of NMDA receptors (Dickenson and Sullivan, 1987 and Woolf, 2011). However, multiple mechanisms appear to participate, including factors released from nonneuronal and immune cells in the spinal cord (Clark and Malcangio, 2011, Guo and Schluesener, 2007 and Marchand et al., 2005). It seems likely that analogous forms of synaptic plasticity will operate at other CNS sites involved in pain processing. Another feature of persistent pain states is dramatically altered gene expression in nociceptors, with at least 10% of the transcriptome being dysregulated in traumatic injury models of neuropathic pain. The change appears to affect a very broad range of genes: the receptors

expressed by nociceptors (e.g., TrpV1, TrpA1, out GABA-B1, 5-HT3A), ion channels regulating nociceptor excitability (e.g., Nav1.8), and transmitters and modulators released centrally (e.g., substance P, BDNF, neuropeptide Y) all display abnormal expression levels (e.g., see Lacroix-Fralish et al., 2006, Maratou et al., 2009 and Lacroix-Fralish et al., 2011 for meta-analysis). Research has started to examine the functional role of some of these genes more specifically. For instance, the reduced expression of the μ-opioid receptor in neuropathic conditions appears to contribute to the limited efficacy of opiates in these states (Lee et al., 2011 and Porreca et al., 1998). Similarly, the increased expression (and activity-dependent release) of BDNF has been proposed to drive some of the central hyperexcitability seen in inflammatory conditions (Pezet et al., 2002). And, the altered expression of particular potassium channel subunits appears to contribute to nociceptor hyperexcitability (Chien et al.

We thus identified the primary cilium and the associated CTR as a signaling center able to convert extrinsic signals into morphological changes to influence cell movements. The mechanism(s) by which Shh signal influenced the organization of the MT GS-1101 mouse cytoskeleton and the subcellular distribution of the endomembrane system in the leading process of MGE cells, is unknown.

This cellular response to Shh signal has never been described previously. It nevertheless provides a cellular basis for better understanding the defects in long distance neuronal migration associated with mutations in centriolar ( Endoh-Yamagami et al., 2010) or basal body proteins, the so-called BBS proteins ( Tobin et al., 2008). It should help to further analyze abnormal cognitive functions associated to defects in primary cilium structure or function. Detailed description of methods in Supplemental Experimental Procedures. Mice from the following strains were used at embryonic or adult stage: Swiss (Janvier, France), Kif3afl/fl, Ift88fl/fl, and Nkx2.1-Cre; Rosa26R-GFP (or YFP). Our experimental procedures were reviewed and approved by the Regional Ethic Committee for Animal Experiment. Cultures prepared on plastic coverslips were fixed, embedded in araldite, contrasted and sectioned in semithin sections. Sections were used to acquire tomography series with an energy-filtered transmission

high-voltage electron microscope. Tomogram reconstruction and 3D models were performed Thymidine kinase with Etomo and IMOD softwares (Boulder University). MGE explants electroporated Selleckchem R428 with expression vectors (pCAG-EGFP, pCAG-Cre, pCAG-PACT-mKO1) were cultured on laminin, on dissociated cortical cells, or on cortical axons. They were imaged with an inverted epifluorescence microscope or with an inverted microscope equipped with a spinning disk, using either a ×40 or a ×63 immersion objective. Organotypic

slices from transgenic mice, and organotypic slices from wild-type mice grafted with MGE explants were cultured in Millicell chambers (Merck Millipore) and imaged with an epifluorescence macroscope (Olympus) or with an inverted microscope equipped with a spinning disk and a ×20 long distance objective. Pharmacological treatments were applied in the culture medium: Shh (N-Ter, R&D Systems, 2.5 μg/ml), SAG (Smo agonist, Calbiochem, 10 μM), or cyclopamine (Sigma-Aldrich, 2μM). Floating sections from embryonic or adult brains were immunostained with antibodies against GFP, parvalbumin, somatostatin, Nkx2.1, Gsx2, or AC3. Cultures were immunostained with antibodies against tubulin, γtubulin, cis-GA (GMAP210, AKAP450), or median GA (CTR433). MT plus- and minus-ends were revealed with EB1 and ninein antibodies. Shh ISH was performed on floating sections from embryonic brains. Softwares for data acquisition and analyses, see Supplemental Experimental Procedures.

To be in line with the recommendation of Preacher and Hayes,36 in the present study, 5000 bootstrap replication samples were drawn with replacement from the data sets.

The results of the CFA among Mainland Chinese students suggested that the 5-factor, 19-item simplified C-BREQ-2 model displayed a poor fit to the data (χ2 (142) = 334.44, p < 0.001; CFI = 0.801; SRMR = 0.094; RMSEA = 0.084 (0.073–0.096)). The standardized factor loadings ranged from 0.39 to 0.80. Inspection of the modification indices buy EPZ-6438 and standardized residual matrix suggested that item 17 (“I get restless if I don’t exercise regularly”), which is in identified regulation subscale, displayed cross-loadings on multiple factors and was associated with multiple standardized residuals. Therefore, removing this item from the model would considerably improve the model fit. Thus, the item was removed from further analysis, and removal of item 17 greatly improved the fit of the 5-factor C-BREQ-2 model (18-item) Tenofovir chemical structure to the data (χ2 (125) = 209.76, p < 0.001; CFI = 0.900; SRMR = 0.069; RMSEA = 0.060 (0.045–0.074)). The fully-standardized item loadings ranged from 0.56 to 0.80. Further examination of the modification indices and standardized residuals of this solution revealed no further factorially complex items. Table 1 displays the item means ± SD, standardized

factor loadings, squared multiple correlations, and bootstrap standard errors for the solution as well as internal consistency reliabilities of subscales. The discriminant validity of the 18-item C-BREQ-2 was supported by the results that none of the 95% CI of inter-factor correlations (Table 2) including the value ± 1.0. This finding suggested Phosphoribosylglycinamide formyltransferase that the C-BREQ-2 assesses distinct constructs. An examination of the inter-factor correlations revealed that the scores from the regulations that were predicted to be closer together on the proposed self-determination

continuum were generally more strongly-correlated than those predicted to be more distal (Table 2). For example, intrinsic motivation had a positive correlation with identified regulation (0.62), a positive correlation with introjected regulation (0.48), and a negative correlation with external regulation (−0.22) and amotivation (−0.39); however, not all hypotheses were supported. For example, the relationship between amotivation and identified regulation (−0.91) was stronger than that between amotivation and intrinsic motivation (−0.39). These findings provide partial support for the nomological validity of the C-BREQ-2. An examination of the correlations among different regulations with theoretically-related motivational consequences suggested that amotivation correlated negatively with subjective vitality, and correlated positively with negative affect.

The cameras emit and measure only infrared light. Therefore, each marker simulates the joints and is used to create a computer generated 3D-model that tracks the movement of each subject (Qualisys Motion Caption System). The 3D position of each marker was used to quantify the joint angle patterns (Qualisys Motion Caption System). The timing of each heel strike from the pressure sensors was used to divide the 30-s trial into gait cycles (MATLAB). The gait cycles were then averaged to determine a typical stride for each joint at each speed

under both conditions per subject. Because the plantar pressure sensors determined the onset of pressure ALK assay of the middle of the heel or the base of the MTP joints, the average gait cycle was then corrected for the initial contact as determined by high-speed light video (208 fps). Timing (sEMG onset, offset, duration) and amplitude of muscle activation were compared between the FFS, RFS, and shifter groups to examine the variability between the three running styles. The muscle activity and kinematic variables were analyzed using analysis of variance (ANOVA), paired and unpaired t tests. Values from the groups were considered significantly different when p < 0.05. All values are reported as mean ± SD. To minimize clutter, we present the values for the representative speed of 3.2 m/s Enzalutamide mouse periodically. The CFFS runners included individuals who always

landed with an FFS under both barefoot and shod conditions, and consisted of 11 individuals: five men and six women; six recreational and five competitive runners. The CRFS runners included 11

individuals who always landed on their heels when barefoot and shod: six men and five women; six recreational and five competitive runners. The shifter group included 18 individuals who ran with an FFS when barefoot and an RFS when shod: 10 men and eight women; seven recreational CTP synthase and 11 competitive. There were no differences between the runners of the three groups in age, weight, height, and hip height (p > 0.05). The joint kinematics for two shifters (1 male, 1 female; 1 recreational, 1 competitive) were unusable and omitted from the dataset. When not considering footwear condition or type of runner, FSA increased slightly with speed (p < 0.05; n = 40; Table 1). FSA, however, varied considerably within each speed and more with footwear condition than with speed (see Section 3.3; Fig. 2, Fig. 3 and Fig. 4). Overall, stride frequency increased by 0.09 Hz per 1 m/s (p < 0.05; n = 39; Table 1; Fig. 3). Average stride length also increased with speed, with an increase of 0.6 m with each 1 m/s (p < 0.05; n = 40; Table 1; Fig. 3). Average duty cycle for the runners decreased by 7.8% per 1 m/s increase in speed (p < 0.05; n = 39; Table 1). Overall, runners generally landed more on their forefeet when barefoot (FSA = −0.2° ± 10.

, 2010 and Chatzigeorgiou and Schafer, 2011).

In Drosophila, class IV multidendritic sensory neurons, the DEG/ENaC Pickpocket (Ppk) is essential for proper responses to harsh mechanical but not thermal selleck stimuli ( Zhong et al., 2010). Ppk is proposed to act upstream of Painless, a TRP ankyrin (TRPA) channel required for behavioral responses to both sensory modalities ( Figure 1A; Zhong et al., 2010). The emerging paradigm of synergy between DEG/ENaCs and TRP channels is bolstered by the present study of ASH neurons ( Figure 1C; Geffeney et al., 2011). In other neurons, TRP channels act as mechanotransduction channels without DEG/ENaC partners. These homo- or heteromeric channels carry nonselective cation currents. For example, Drosophila NompC/TRPN1 is required for hearing, touch, and proprioception ( Arnadóttir and Chalfie, 2010). Null mutations dramatically reduce transient mechanosensitive currents in

external sensory organs ( Figure 1B; Arnadóttir and Chalfie, 2010). A residual nonadapting current suggests that multiple conductances underlie mechanotransduction, which might explain incomplete deafness in nompC mutants ( Arnadóttir and Chalfie, 2010). The C. elegans TRPN homolog TRP-4 mediates mechanotransduction currents in cephalic CEP and posterior PDE neurons ( Kang et al., 2010 and Li et al., 2011). TRP-4 makes the short list of bona fide mechanosensory transduction channels, as pore mutations alter the selectivity of touch-evoked currents in vivo ( Kang et al., selleck chemicals 2010). Although TRPN channels are critical for mechanotransduction in these invertebrate neurons, mammals lack TRPN molecules. By contrast, TRP vanilloid (TRPV) channels much are conserved among invertebrates and vertebrates. The first TRPV channel implicated in touch was osm-9, which is expressed in C. elegans ASH neurons ( Arnadóttir and Chalfie, 2010). ASH, a pair of sensory neurons whose cilia are exposed to the environment, detect chemical irritants,

hyperosmolarity and touch (Figure 1C; Arnadóttir and Chalfie, 2010). Because they initiate avoidance behavior in response to harmful stimuli, ASH neurons are viewed as polymodal nociceptors. ASH expresses two DEG/ENaCs, deg-1 and unc-8. These isoforms were discounted as candidate mechanotransduction channels in ASH because mutants display normal behavioral responses to nose touch ( Chalfie and Wolinsky, 1990 and Tavernarakis et al., 1997). By contrast, osm-9 mutations disrupt avoidance of aversive stimuli. Consistent with a role in sensory transduction, OSM-9 localizes to sensory cilia and this requires a second TRPV channel, OCR-2 ( Figure 1C). Although osm-9 mutations attenuate touch-evoked behaviors and Ca2+ signals in ASH ( Hilliard et al., 2005), it was unknown whether mechanotransduction currents were also affected. Geffeney et al.

The first response to mechanical stimulus was not affected, but the magnitude of the learn more second response was reduced (Kindt et al., 2007). A role for the TRPV channel subunit OSM-9 is evident from the finding that osm-9 mutant OLQ neurons lack mechanically-evoked calcium transients ( Chatzigeorgiou et al., 2010). Because MRCs have yet to be measured in this mechanoreceptor neuron, it is not known whether loss of TRPA-1 or OSM-9 affect MRCs or the events that follow their activation. These examples in C. elegans nematodes establish the rule that mechanoreceptor neurons commonly express multiple

DEG/ENaC and TRP channel proteins and that these channels operate together to enable proper sensory function. The ability to directly measure

MRCs in vivo has revealed that both DEG/ENaC and TRP channels can form MeT channels. Evidence from the ASH and PVD nociceptors suggests that some TRP channels are essential for posttransduction events needed for sensory signaling. These case studies provide evidence for the idea that TRP channels can be crucial elements in both sensory transduction and in post-transduction signaling. They also illustrate the powerful insights available when detailed physiological analysis of identified mechanoreceptor neurons is merged with genetic dissection. It is rare for deletion of a single DEG/ENaC gene to induce strong behavioral defects in C. elegans. Indeed, there is only one such DEG/ENaC gene known so far: mec-4. By contrast, deleting the DEG/ENaC genes mec-10, deg-1, unc-8, and unc-105 fails to produce clear behavioral phenotypes, although gain-of-function alleles significantly disrupt several behaviors. click here Though only a subset of the DEG/ENaC genes have been studied in this way, these findings suggest there is considerable redundancy in C. elegans mechanosensation. The case of mec-4 and mec-10 illustrate this idea clearly: both genes are coexpressed in the TRNs and encode pore-forming subunits of the MeT channel required for gentle touch sensation ( O’Hagan et al.,

2005). Whereas deleting mec-4 eliminates mechanoreceptor currents and behavioral responses to touch, deleting mec-10 produces a mild defect in touch sensation and has little effect on Terminal deoxynucleotidyl transferase mechanoreceptor currents ( Arnadóttir et al., 2011). The peripheral nervous system of Drosophila larvae has three main types of neurons ( Bodmer et al., 1987, Bodmer and Jan, 1987 and Ghysen et al., 1986). External sensory and chordotonal neurons have a single sensory dendrite and innervate specific mechanosensory organs. In contrast, multidendritic neurons have a variable number of fine dendritic processes that lie beneath the epidermis and do not innervate a specific structure. Different subclasses of these neurons provide information about touch and body position as well as function as nociceptors ( Hughes and Thomas, 2007, Song et al., 2007 and Zhong et al., 2010).

N., 17023021, 21220006 and 23650204 to M.K., 17023001 and 19100005 to M.W., 18019007 and 18300102 to Y.Y.), the Strategic Research Program for Brain Sciences (Development of Biomarker Candidates for Social Behavior), and Global COE program (Integrative Life Science Based on the Study of Biosignaling Mechanisms) from MEXT, Japan. “
“The motor cortex has long been known to play a central role in the generation of movement (Fritsch and Hitzig, 1870), but fundamental questions remain to be answered about the functional organization of its subregions and their neuronal circuits. Results from electrical brain stimulation have traditionally been interpreted with an emphasis on somatotopy

(Penfield and Boldrey, 1937 and Asanuma and Rosén, 1972), but the utility

of this principle has diminished with the discovery of multiple representations of the body (Neafsey and Sievert, 1982, Luppino Inhibitor Library manufacturer et al., 1991 and Schieber, 2001). A more nuanced view has since developed, with recordings made during voluntary movements in monkeys demonstrating that neurons in motor cortex encode information related to the force (Evarts, 1968), direction (Georgopoulos et al., 1986), and speed Sunitinib mouse of movements (Moran and Schwartz, 1999 and Churchland et al., 2006). The activity of cortical neurons also reflects both preparation for movement (Sanes and Donoghue, 1993 and Paz et al., 2003) and the interpretation of actions performed by others (Gallese et al., 1996 and Hari

et al., 1998). Recently, experimentation with prolonged trains of stimulation has suggested that the brain’s multiple motor representations may be organized according to classes of behavior (Graziano et al., 2002, Stepniewska et al., 2005 and Ramanathan et al., 2006). Despite the detailed knowledge gleaned from these efforts, our understanding of the macroscopic organization of motor cortex remains incomplete. Much of our understanding about the motor cortex comes from experiments in which stimulation or recording is performed at a few cortical points. Technical limitations have traditionally made it difficult to probe the cortical circuitry underlying motor representations in a Terminal deoxynucleotidyl transferase uniform, quantitative manner. Recently, we and others have developed a novel method for rapid automated motor mapping based on light activation of Channelrhodopsin-2 (ChR2) that has facilitated experiments which were previously impossible (Ayling et al., 2009, Hira et al., 2009 and Komiyama et al., 2010). This technique has the advantage of objectively and reproducibly sampling the movements evoked by stimulation at hundreds of cortical locations in mere minutes. Here, we apply light-based motor mapping to investigate the functional subdivisions of the motor cortex and their dependence on intracortical activity.

, 2001). Pericytes are packed at the abluminal side of cerebral endothelial cells, controlling endothelial functions, and therefore play a central

role in integrating luminal signals generated from cerebral MI-773 endothelial cells to CNS parenchyma (Hermann and Elali, 2012). Recent reports have shown that pericytes play an important role in CNS immunity at many levels. Being contractile cells, dysfunction of these cells reduces CNS microcirculation, deregulating regional cerebral blood flow (rCBF), which takes place before immune reaction (Fernández-Klett et al., 2010; Bell et al., 2010). Nitrosative stress induced by initiation of the innate immune response has a deep impact on pericyte functions by inducing continuous contraction, which results in blood entrapment in CNS capillary LGK-974 beds (Yemisci et al., 2009), exacerbating the local immune responses. Moreover, numerous studies have outlined a possible function of pericytes as macrophages in the CNS based on the presence of a high number of lysosomes within their cytoplasm (Xiong et al., 2009), their efficient capacity of internalizing tracers injected in blood

circulation, and cerebrospinal fluid (CSF) (Rucker et al., 2000), along with a potential for phagocytosis (Balabanov et al., 1996) and antigen presentation capacities (Hickey and Kimura, 1988). Pericytes isolated from lung and CNS vasculature express functional TLR4, the activation of which regulated endothelial function and affected vascular permeability (Edelman et al., 2007; Balabanov et al., 1996). Moreover, some studies showed that, while quiescent under PtdIns(3,4)P2 physiological conditions, pericytes

are capable of inducing their macrophage-like activity after TLR4 signaling induction (Graeber et al., 1990; Balabanov et al., 1996). Under such conditions, pericytes produce immune-active molecules, such as nitric oxide (NO), and a wide range of cytokines and chemokines, namely granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), CCL3, and CCL4 (Kovac et al., 2011) (Figure 3). Recently, pericytes have been given special attention for their roles in neurodegenerative diseases, namely AD. Pericytes induce BBB formation, mainly by downregulating genes associated with vascular permeability (Daneman et al., 2010) and inducing the activity of ABCB1 in brain endothelial cells (Al Ahmad et al., 2011). Loss of pericytes has been proposed to initiate the pathogenesis of neurodegenerative diseases by causing a primary cerebral vascular injury (Winkler et al., 2011). Consequently, the primary vascular injury leads to the extravasation of blood-borne molecules into brain parenchyma, leading to neuronal death (Winkler et al., 2011).

6 to 26.9 nM) as assessed in a similar assay (Siddiqui et al., 2010), suggesting that this interaction is of physiological relevance. Thus, LRRTM4 binds with high affinity to glypicans and syndecans via their HS chains. To determine whether LRRTM4 and HSPGs interact in trans on cellular surfaces and recruit each other to developing contact sites, we cocultured COS7 cells expressing LRRTM4 with www.selleckchem.com/products/Romidepsin-FK228.html neurons expressing HSPGs and vice versa. LRRTM4-CFP expressed in COS7 cells was able to recruit neuronally expressed HA-GPC5

or HA-SDC2 but not HA-GPC5ΔGAG to contact sites ( Figures 3A and 3B). HA-GPC5 targeted selectively to axons in cultured hippocampal neurons, both in pure neuron cultures and in the COS7 cocultures ( Figure S3). HA-SDC2 targeted PF-02341066 purchase to both axons and dendrites, although LRRTM4-expressing COS7 cells induced local aggregation of both recombinant HSPGs mainly along contacting axons in coculture. This result indicates that LRRTM4 on dendrites could recruit axonal HSPGs to contact sites. Conversely, Myc-GPC5 or Myc-SDC2 but not Myc-GPC5ΔGAG expressed in COS7 cells could recruit neuronally expressed mCherry-LRRTM4 to contact sites ( Figures 3C and 3D). Consistent with the somatodendritic targeting of recombinant LRRTM4 in pure neuron cultures ( Figure 1),

HSPG-expressing COS7 cells induced local aggregation of recombinant LRRTM4 along contacting dendrites but not axons in coculture. This result indicates that HSPGs

on axons could recruit dendritic LRRTM4 to contact sites. The absence of recruitment activity by Myc-GPC5ΔGAG indicates that the HS chains are required for the mutual recruitment of LRRTM4 and HSPGs to cell contact sites. To assess the role of the LRRTM4-HSPG interaction in synaptic development, we built on our finding that heparinase-mediated cleavage of the HS chains of glypicans and syndecans disrupts their interaction with LRRTM4-Fc in the cell-based binding assay Baf-A1 manufacturer (Figure 2). If the LRRTM4-HSPG interaction is necessary for the ability of neuronally overexpressed LRRTM4 to increase presynaptic inputs, heparinase cotreatment should block the effects of neuronal overexpression of LRRTM4 on presynaptic inputs. Indeed, using two distinct markers for presynaptic inputs, the active zone protein bassoon and the vesicle-associated protein synapsin, we found that overexpression of YFP-LRRTM4 in cultured neurons increased immunofluorescence for presynaptic markers onto expressing dendrites and that this effect was abolished by cotreatment with heparinases (Figures 4A and 4B). To test the specificity of the effects of heparinases, we did parallel experiments with another synaptogenic protein NGL-3 (Woo et al., 2009), which we found to be of similar potency as LRRTM4.

The example cell in Figure 8C increased firing rate when aspect ratio dimension was modified but not when the intereye distance changed (Figure S7A). To determine whether cells were significantly tuned for each one of the 19 geometrical feature

dimensions, we repeated the analysis described in Freiwald et al. (2009) and computed RG7204 research buy the heterogeneity index (Figure S7B, see Experimental Procedures). Out of the 35 face-selective cells, 29 were modulated by at least one geometrical feature (Figures 8D and S7C), where the most common feature was aspect ratio (Figure S7D). Cells were also modulated by contrast polarity features (Figure 8D). Out of the 35 cells, 19 were modulated by at least one contrast polarity feature. Overall, 49% of the cells were modulated by both types of features (Figures 8E and S7E). Thus, tuning to low-spatial frequency coarse contrast features and to high-spatial frequency geometrical features can co-occur in face-selective cells, suggesting that some cells encode information relevant for both detection and recognition. One of the most see more basic questions about face-selective cells in IT cortex is how they derive their striking selectivity for faces. Motivated by computational models for object detection

that emphasize the importance of features derived from local contrast (Lienhart and Jochen, 2002, Sinha et al., 2006 and Viola and Jones, 2001), this study focused on the question of whether contrast features are essential for driving face-selective cells. Our main strategy was to probe cells with a parameterized stimulus set, allowing manipulation of local luminance in each face part. The results suggest that detection of contrast features is a critical step used by the brain to generate face-selective responses. Four pieces

of evidence support DOK2 this claim. First, different combinations of contrasts could drive cells from no response to responses greater than that to a real face. Second, the polarity preference for individual features was remarkably consistent across the population in three monkeys. Third, the contrast feature preference followed with exquisite precision features that have been found to be predictive of the presence of a face in an image; these features are illumination invariant, agree with human psychophysics (Sinha et al., 2006) and fMRI studies (George et al., 1999 and Gilad et al., 2009), and are ubiquitously used in artificial real-time face detection (Lienhart and Jochen, 2002 and Viola and Jones, 2001). Finally, the tuning to contrast features generalized from our artificial collage of parts to real face images. Shape selectivity in IT has been proposed to arise from cells representing different feature combinations (Brincat and Connor, 2004, Fujita et al., 1992, Tanaka, 2003 and Tsunoda et al., 2001).