Secondary Visual Cortex Research Articles

201. Understanding Altered Eye Gaze Perception in Schizophrenia Using Dynamic Causal Modeling

Abstract Background: Previous studies have shown abnormal eye gaze perception in schizophrenia, associated with compromised social functioning. However, the neural mechanisms of altered gaze perception in schizophrenia remain unclear, limiting our ability to design effective interventions. This study aims to use dynamic causal modeling (DCM) of functional MRI time-series data to reveal aberrant dynamics between brain regions associated with eye gaze perception in schizophrenia. Methods: Twenty-five patients with schizophrenia or schizoaffective disorder (SZ) and 20 healthy controls (HC) completed a gaze perception task during BOLD fMRI. Participants viewed faces with different gaze angles and decided either the gaze direction (Gaze: “Looking at you?” yes/no) or gender of the face (Gender: male/female). Four nodes were identified as regions of interest for DCM as they showed differential activation between Gaze and Gender: secondary visual cortex (Vis), temporo-parietal junction (TPJ), anterior insula (aIns), and medial prefrontal cortex (mPFC). A bilinear model space was generated with these 4 nodes, as well as visual input of face, self-connections, bidirectional connections between nodes, and modulation of gaze on the connections. Results: Bayesian model selection revealed a winning model, in which Vis showed bottom-up influence on mPFC, which in turn had direct top-down influences on aIns and TPJ and indirect top-down influence on Vis through TPJ; attending to gaze modulated the Vis-mPFC and mPFC-TPJ connections. Group difference was observed in the Gaze modulation on the Vis-mPFC connection, such that attending to gaze inhibited the bottom-up connection from Vis to mPFC but this inhibition was weakened in SZ relative to HC. Conclusion: These findings suggest that when determining the self-referential nature of social information, it is critical to suppress stimulus-driven processing and rely more on conceptually-driven cognition formulated from past experience. A reduced ability to do so may underlie the abnormalities observed in eye gaze perception in schizophrenia.

Parahippocampal and retrosplenial connections of rat posterior parietal cortex.

The posterior parietal cortex has been implicated in spatial functions, including navigation. The hippocampal and parahippocampal region and the retrosplenial cortex are crucially involved in navigational processes and connections between the parahippocampal/retrosplenial domain and the posterior parietal cortex have been described. However, an integrated account of the organization of these connections is lacking. Here, we investigated parahippocampal connections of each posterior parietal subdivision and the neighboring secondary visual cortex using conventional retrograde and anterograde tracers as well as transsynaptic retrograde tracing with a modified rabies virus. The results show that posterior parietal as well as secondary visual cortex entertain overall sparse connections with the parahippocampal region but not with the hippocampal formation. The medial and lateral dorsal subdivisions of posterior parietal cortex receive sparse input from deep layers of all parahippocampal areas. Conversely, all posterior parietal subdivisions project moderately to dorsal presubiculum, whereas rostral perirhinal cortex, postrhinal cortex, caudal entorhinal cortex and parasubiculum all receive sparse posterior parietal input. This indicated that the presubiculum might be a major liaison between parietal and parahippocampal domains. In view of the close association of the presubiculum with the retrosplenial cortex, we included the latter in our analysis. Our data indicate that posterior parietal cortex is moderately connected with the retrosplenial cortex, particularly with rostral area 30. The relative sparseness of the connectivity with the parahippocampal and retrosplenial domains suggests that posterior parietal cortex is only a modest actor in forming spatial representations underlying navigation and spatial memory in parahippocampal and retrosplenial cortex. © 2017 Wiley Periodicals, Inc.

Hierarchical Feature Extraction Assisted with Visual Saliency for Image Quality Assessment

Image quality assessment (IQA) is desired to evaluate the perceptual quality of an image in a manner consistent with subjective rating. Considering the characteristics of hierarchical visual cortex, a novel full reference IQA method is proposed in this paper. Quality-aware features that human visual system is sensitive to are extracted to describe image quality comprehensively. Concretely, log Gabor filters and local tetra patterns are employed to capture spatial frequency and local texture features, which are attractive to the primary and secondary visual cortex, respectively. Moreover, images are enhanced before feature extraction with the assistance of visual saliency maps since visual attention affects human evaluation of image quality. The similarities between the features extracted from distorted image and corresponding reference images are synthesized and mapped into an objective quality score by support vector regression. Experiments conducted on four public IQA databases show that the proposed method outperforms other state-of-the-art methods in terms of both accuracy and robustness; that is, it is highly consistent with subjective evaluation and is robust across different databases.

Short Latency Gray Matter Changes in Voxel-Based Morphometry following High Frequent Visual Stimulation.

Magnetic resonance imaging studies using voxel-based morphometry (VBM) detected structural changes in the human brain within periods of months or weeks. The underlying molecular mechanisms of VBM findings remain unresolved. We showed that simple visual stimulation by an alternating checkerboard leads to instant, short-lasting alterations of the primary and secondary visual cortex detected by VBM. The rapidness of occurrence (i.e., within 10 minutes) rather excludes most of the proposed physiological mechanism such as neural or glial cell genesis/degeneration or synapse turnover. We therefore favour cerebral fluid shifts to be the underlying correlate of the here observed VBM gray matter changes. Fast onset gray matter changes might be one important explanation for the inconsistency of VBM study results that often raise concern in regard to the validity of presented data. This study shows that changes detectable by VBM may occur within a few minutes after physiological stimulation and must be considered in future VBM experiments to avoid misinterpretation of results.

Functional neuroimaging of visuo-vestibular interaction

The brain combines visual, vestibular and proprioceptive information to distinguish between self- and world motion. Often these signals are complementary and indicate that the individual is moving or stationary with respect to the surroundings. However, conflicting visual motion and vestibular cues can lead to ambiguous or false sensations of motion. In this study, we used functional magnetic resonance imaging to explore human brain activation when visual and vestibular cues were either complementary or in conflict. We combined a horizontally moving optokinetic stimulus with caloric irrigation of the right ear to produce conditions where the vestibular activation and visual motion indicated the same (congruent) or opposite directions of self-motion (incongruent). Visuo-vestibular conflict was associated with increased activation in a network of brain regions including posterior insular and transverse temporal areas, cerebellar tonsil, cingulate and medial frontal gyri. In the congruent condition, there was increased activation in primary and secondary visual cortex. These findings suggest that when sensory information regarding self-motion is contradictory, there is preferential activation of multisensory vestibular areas to resolve this ambiguity. When cues are congruent, there is a bias towards visual cortical activation. The data support the view that a network of brain areas including the posterior insular cortex may play an important role in integrating and disambiguating visual and vestibular cues.

19. Visual cortex representation of the vertical meridian

Two neural mechanisms warrant transmission of visual information to both hemispheres: the corpus callosum, most represented at secondary visual cortices (V2–V3–V4–V5); the 0.5 deg wide band of nasal retina near the fovea, which contains ganglion cells projecting to ipsilateral LGN/striate cortex intermingled with cells that project contralaterally. We investigated visual projections at the vertical meridian of the visual field to the visual cortex, by studying visual evoked potentials (VEPs) in ten healthy subjects. With binocular viewing of the pattern reversal checkerboard, we used either left/right hemifield stimulation either upper/lower hemifield stimulation. Alternating right and left hemifield stimulation with extension of edges across the vertical meridian (binding recordings) and complementary reversal (unbinding recordings) was used for test recordings. Alternating upper and lower hemifield stimulation were used as control recordings. N75 did not differ in binding/unbinding and control recordings. P100 and N145 amplitude were higher - and P100 latency shorter – during binding than unbinding recordings. Control recordings showed no difference between upper/ lower hemifield stimulation. These findings suggest that visual stimuli with extension of edges across the vertical meridian are mainly represented at the level of visual peristriate areas.

Embedding Task-Based Neural Models into a Connectome-Based Model of the Cerebral Cortex.

A number of recent efforts have used large-scale, biologically realistic, neural models to help understand the neural basis for the patterns of activity observed in both resting state and task-related functional neural imaging data. An example of the former is The Virtual Brain (TVB) software platform, which allows one to apply large-scale neural modeling in a whole brain framework. TVB provides a set of structural connectomes of the human cerebral cortex, a collection of neural processing units for each connectome node, and various forward models that can convert simulated neural activity into a variety of functional brain imaging signals. In this paper, we demonstrate how to embed a previously or newly constructed task-based large-scale neural model into the TVB platform. We tested our method on a previously constructed large-scale neural model (LSNM) of visual object processing that consisted of interconnected neural populations that represent, primary and secondary visual, inferotemporal, and prefrontal cortex. Some neural elements in the original model were “non-task-specific” (NS) neurons that served as noise generators to “task-specific” neurons that processed shapes during a delayed match-to-sample (DMS) task. We replaced the NS neurons with an anatomical TVB connectome model of the cerebral cortex comprising 998 regions of interest interconnected by white matter fiber tract weights. We embedded our LSNM of visual object processing into corresponding nodes within the TVB connectome. Reciprocal connections between TVB nodes and our task-based modules were included in this framework. We ran visual object processing simulations and showed that the TVB simulator successfully replaced the noise generation originally provided by NS neurons; i.e., the DMS tasks performed with the hybrid LSNM/TVB simulator generated equivalent neural and fMRI activity to that of the original task-based models. Additionally, we found partial agreement between the functional connectivities using the hybrid LSNM/TVB model and the original LSNM. Our framework thus presents a way to embed task-based neural models into the TVB platform, enabling a better comparison between empirical and computational data, which in turn can lead to a better understanding of how interacting neural populations give rise to human cognitive behaviors.

The impact of early environmental interventions on structural plasticity of the axon initial segment in neocortex.

Plasticity of the axon initial segment (AIS) is a newly discovered type of structural plasticity that regulates cell excitability. AIS plasticity has been reported to happen during normal development of neocortex and also in a few pathological conditions involving disruption of the inhibition/excitation balance. Here we report on the impact of early environmental interventions on structural plasticity of AIS in the mouse neocortex. C57BL/6 mice were raised in standard or enriched environment (EE) from birth up to the time of experiments and were injected with saline or MK-801 [N-Methyl-D-Aspartate (NMDA) receptor antagonist, 1 mg/kg] on postnatal days (P) 6-10. We used Ankyrin G immunoreactivity to mark the AIS of cortical neurons in two sub-regions of frontal cortex (frontal association area, FrA and secondary motor cortex, M2) and in the secondary visual cortex (V2). In 1-month-old mice, the mean AIS length differed between three areas, with the shortest AISs being observed in V2. Postnatal MK-801 or EE led to shortening of AIS only in the frontal areas. However, exposure to EE restored AIS shortening induced by MK-801. Chronic postnatal MK-801 results in structural plasticity of AIS exclusive to the frontal cortex. EE may modify underlying neuronal mechanisms resulting in restoration of AIS length.

Motor and mental training in older people: Transfer, interference, and associated functional neural responses

Learning new motor skills may become more difficult with advanced age. In the present study, we randomized 56 older individuals, including 30 women (mean age 70.6 years), to 6 weeks of motor training, mental (motor imagery) training, or a combination of motor and mental training of a finger tapping sequence. Performance improvements and post-training functional magnetic resonance imaging (fMRI) were used to investigate performance gains and associated underlying neural processes. Motor-only training and a combination of motor and mental training improved performance in the trained task more than mental-only training. The fMRI data showed that motor training was associated with a representation in the premotor cortex and mental training with a representation in the secondary visual cortex. Combining motor and mental training resulted in both premotor and visual cortex representations. During fMRI scanning, reduced performance was observed in the combined motor and mental training group, possibly indicating interference between the two training methods. We concluded that motor and motor imagery training in older individuals is associated with different functional brain responses. Furthermore, adding mental training to motor training did not result in additional performance gains compared to motor-only training and combining training methods may result in interference between representations, reducing performance.

Consolidation of altered associability information by amygdala central nucleus

The surprising omission of a reinforcer can enhance the associability of the stimuli that were present when the reward prediction error was induced, so that they more readily enter into new associations in the future. Previous research from this laboratory identified brain circuit elements critical to the enhancement of stimulus associability by the omission of an expected event and to the subsequent expression of that altered associability in more rapid learning. These elements include the amygdala, the midbrain substantia nigra, the basal forebrain substantia innominata, the dorsolateral striatum, the secondary visual cortex, and the posterior parietal cortex. Here, we found that consolidation of a surprise-enhanced associability memory in a serial prediction task depends on processing in the amygdala central nucleus (CeA) after completion of sessions that included the surprising omission of an expected event. Post-surprise infusions of anisomycin, lidocaine, or muscimol prevented subsequent display of surprise-enhanced associability. Because previous studies indicated that CeA function is unnecessary for the expression of associability enhancements that were induced previously when CeA function was intact (Holland & Gallagher, 2006), we interpreted these results as indicating that post-surprise activity of CeA (“surprise replay”) is necessary for the consolidation of altered associability memories elsewhere in the brain, such as the posterior parietal cortex (Schiffino et al., 2014a).

Congenital Anophthalmia and Binocular Neonatal Enucleation Differently Affect the Proteome of Primary and Secondary Visual Cortices in Mice.

In blind individuals, visually deprived occipital areas are activated by non-visual stimuli. The extent of this cross-modal activation depends on the age at onset of blindness. Cross-modal inputs have access to several anatomical pathways to reactivate deprived visual areas. Ectopic cross-modal subcortical connections have been shown in anophthalmic animals but not in animals deprived of sight at a later age. Direct and indirect cross-modal cortical connections toward visual areas could also be involved, yet the number of neurons implicated is similar between blind mice and sighted controls. Changes at the axon terminal, dendritic spine or synaptic level are therefore expected upon loss of visual inputs. Here, the proteome of V1, V2M and V2L from P0-enucleated, anophthalmic and sighted mice, sharing a common genetic background (C57BL/6J x ZRDCT/An), was investigated by 2-D DIGE and Western analyses to identify molecular adaptations to enucleation and/or anophthalmia. Few proteins were differentially expressed in enucleated or anophthalmic mice in comparison to sighted mice. The loss of sight affected three pathways: metabolism, synaptic transmission and morphogenesis. Most changes were detected in V1, followed by V2M. Overall, cross-modal adaptations could be promoted in both models of early blindness but not through the exact same molecular strategy. A lower metabolic activity observed in visual areas of blind mice suggests that even if cross-modal inputs reactivate visual areas, they could remain suboptimally processed.

Secondary visual cortex is critical to the expression of surprise-induced enhancements in cue associability in rats.

Considerable evidence indicates that reinforcement prediction error, the difference between the obtained and expected reinforcer values, modulates attention to potential cues for reinforcement. The surprising delivery or omission of a reinforcer enhances the associability of the stimuli that were present when the error was induced, so that they more readily enter into new associations in the future. Previous research from our laboratory identified brain circuit elements critical to the enhancement of stimulus associability by omission of an expected event and to the subsequent expression of that altered associability in more rapid learning. A key finding was that the rat posterior parietal cortex was essential during the encoding, consolidation and retrieval of associability memories that were altered by the surprising omission of an expected event in a serial prediction task. Here, we found that the function of adjacent secondary visual cortex was critical only to the expression of altered cue associability in that same task. This specialization of function is discussed in the context of broader cortical and subcortical networks for modulation of attention in associative learning, as well as recent anatomical investigations that suggest that the rodent posterior parietal cortex overlaps with and may subsume secondary visual cortex.

Posterior parietal cortex of the rat: Architectural delineation and thalamic differentiation.

This study refines the characterization of the rat parietal cortical domain in terms of cyto- and chemoarchitecture as well as thalamic connectivity. We recognize three subdivisions of the posterior parietal cortex (PPC), which are architectonically distinct from the neighboring somatosensory and visual cortices. Furthermore, we show that the different parietal areas are differently connected with thalamic nuclei. The medial portion of PPC (mPPC) is connected primarily with the medial portion of the lateral posterior nucleus (LP), whereas the lateral portion (lPPC) connects with the posterior complex (Po). The more caudolateral part of PPC (PtP) also projects to Po but can be distinguished from lPPC based on architectonic criteria. The primary somatic and visual cortices, neighboring PPC, are preferentially connected with the primary ventral posterior and dorsolateral geniculate nuclei, respectively, and less with the associational Po and LP. Particularly the border between the secondary visual cortex and the PPC has been a matter of controversy, but here we show that, although PPC subareas are connected with Po and medial LP, the medial and lateral secondary visual cortices are connected with lateral LP and a portion of medial LP different from that connected with PPC. The resulting delineations and specifications of connectivity with thalamic nuclei together with upcoming studies of cortical connectivity will facilitate detailed studies on the role of the subdivisions of PPC in the rat as diverse, higher order associative cortical areas, comparable to those described in the primate.for J. Comp. Neurol. 524:3774-3809, 2016. © 2016 Wiley Periodicals, Inc.

Interplay between non-NMDA and NMDA receptor activation during oscillatory wave propagation: Analyses of caffeine-induced oscillations in the visual cortex of rats

Generation and propagation of oscillatory activities in cortical networks are important features of the brain. However, many issues related to oscillatory phenomena are unclear. We previously reported neocortical oscillation following caffeine treatment of rat brain slices. Input to the primary visual cortex (Oc1) generates N-methyl-d-aspartate (NMDA) receptor-dependent oscillations, and we proposed that the oscillatory signals originate in the secondary visual cortex (Oc2). Because non-NMDA and NMDA receptors cooperate in synaptic transmission, non-NMDA receptors may also play an important role in oscillatory activities. Here we investigated how non-NMDA receptor activities contribute to NMDA receptor-dependent oscillations by using optical recording methods. After induction of stable oscillations with caffeine application, blockade of NMDA receptors abolished the late stable oscillatory phase, but elicited ‘hidden’ non-NMDA receptor-dependent oscillation during the early depolarizing phase. An interesting finding is that the origin of the non-NMDA receptor-dependent oscillation moved from the Oc1, during the early phase, toward the origin of the NMDA receptor-dependent oscillation that is fixed in the Oc2. In addition, the frequency of the non-NMDA receptor-dependent oscillation was higher than that of the NMDA receptor-dependent oscillation. Thus, in one course of spatiotemporal oscillatory activities, the relative balance in receptor activities between non-NMDA and NMDA receptors gradually changes, and this may be due to the different kinetics of the two receptor types. These results suggest that interplay between the two receptor types in the areas of Oc1 and Oc2 may play an important role in oscillatory signal communication.

A novel approach for locating mice brain regions of Cryptococcus neoformans CNS invasion

Aim of this study was to locate the brain regions where Cryptococcus interact with brain cells and invade into brain. After 7 days of intratracheal inocula-tion of GFP-tagged Cryptococcus neoformans strains H99, serial cryosections (10 ?m) from 3 C57 BL/6 J mice brains were imaged with immunofluorescence microscopy. GFP-tagged H99 were found in some brain regions such as primary motor cortex-secondary motor cortex, caudate putamen, stratum lucidum of hippocampus, field CA1 of hippocampus, dorsal lateral geniculate nucleus, lateral posterior thalamic nucleus, laterorostral part, lateral posterior thalamic nucleus, mediorostral part, retrosplenial agranular cortex, lateral area of secondary visual cortex, and lacunosum molecular layer of the hippocampus. The results will be very useful for further exploring the mechanism of C. neoformans infection of brain.

Functional Connectivity Hubs and Networks in the Awake Marmoset Brain.

In combination with advances in analytical methods, resting-state fMRI is allowing unprecedented access to a better understanding of the network organization of the brain. Increasing evidence suggests that this architecture may incorporate highly functionally connected nodes, or “hubs”, and we have recently proposed local functional connectivity density (lFCD) mapping to identify highly-connected nodes in the human brain. Here, we imaged awake nonhuman primates to test whether, like the human brain, the marmoset brain contains FC hubs. Ten adult common marmosets (Callithrix jacchus) were acclimated to mild, comfortable restraint using individualized helmets. Following restraint training, resting BOLD data were acquired during eight consecutive 10 min scans for each subject. lFCD revealed prominent cortical and subcortical hubs of connectivity across the marmoset brain; specifically, in primary and secondary visual cortices (V1/V2), higher-order visual association areas (A19M/V6[DM]), posterior parietal and posterior cingulate areas (PGM and A23b/A31), thalamus, dorsal and ventral striatal areas (caudate, putamen, lateral septal nucleus, and anterior cingulate cortex (A24a). lFCD hubs were highly connected to widespread areas of the brain, and further revealed significant network-network interactions. These data provide a baseline platform for future investigations in a nonhuman primate model of the brain’s network topology.

PET Mapping for Brain-Computer Interface Stimulation of the Ventroposterior Medial Nucleus of the Thalamus in Rats with Implanted Electrodes.

Brain-computer interface (BCI) technology has great potential for improving the quality of life for neurologic patients. This study aimed to use PET mapping for BCI-based stimulation in a rat model with electrodes implanted in the ventroposterior medial (VPM) nucleus of the thalamus. PET imaging studies were conducted before and after stimulation of the right VPM. Stimulation induced significant orienting performance. (18)F-FDG uptake increased significantly in the paraventricular thalamic nucleus, septohippocampal nucleus, olfactory bulb, left crus II of the ansiform lobule of the cerebellum, and bilaterally in the lateral septum, amygdala, piriform cortex, endopiriform nucleus, and insular cortex, but it decreased in the right secondary visual cortex, right simple lobule of the cerebellum, and bilaterally in the somatosensory cortex. This study demonstrated that PET mapping after VPM stimulation can identify specific brain regions associated with orienting performance. PET molecular imaging may be an important approach for BCI-based research and its clinical applications.

Neural coding of image structure and contrast polarity of Cartesian, hyperbolic, and polar gratings in the primary and secondary visual cortex of the tree shrew.

We comprehensively characterize spiking and visual evoked potential (VEP) activity in tree shrew V1 and V2 using Cartesian, hyperbolic, and polar gratings. Neural selectivity to structure of Cartesian gratings was higher than other grating classes in both visual areas. From V1 to V2, structure selectivity of spiking activity increased, whereas corresponding VEP values tended to decrease, suggesting that single-neuron coding of Cartesian grating attributes improved while the cortical columnar organization of these neurons became less precise from V1 to V2. We observed that neurons in V2 generally exhibited similar selectivity for polar and Cartesian gratings, suggesting that structure of polar-like stimuli might be encoded as early as in V2. This hypothesis is supported by the preference shift from V1 to V2 toward polar gratings of higher spatial frequency, consistent with the notion that V2 neurons encode visual scene borders and contours. Neural sensitivity to modulations of polarity of hyperbolic gratings was highest among all grating classes and closely related to the visual receptive field (RF) organization of ON- and OFF-dominated subregions. We show that spatial RF reconstructions depend strongly on grating class, suggesting that intracortical contributions to RF structure are strongest for Cartesian and polar gratings. Hyperbolic gratings tend to recruit least cortical elaboration such that the RF maps are similar to those generated by sparse noise, which most closely approximate feedforward inputs. Our findings complement previous literature in primates, rodents, and carnivores and highlight novel aspects of shape representation and coding occurring in mammalian early visual cortex.

Spatial structure of neuronal receptive field in awake monkey secondary visual cortex (V2)

Visual processing depends critically on the receptive field (RF) properties of visual neurons. However, comprehensive characterization of RFs beyond the primary visual cortex (V1) remains a challenge. Here we report fine RF structures in secondary visual cortex (V2) of awake macaque monkeys, identified through a projection pursuit regression analysis of neuronal responses to natural images. We found that V2 RFs could be broadly classified as V1-like (typical Gabor-shaped subunits), ultralong (subunits with high aspect ratios), or complex-shaped (subunits with multiple oriented components). Furthermore, single-unit recordings from functional domains identified by intrinsic optical imaging showed that neurons with ultralong RFs were primarily localized within pale stripes, whereas neurons with complex-shaped RFs were more concentrated in thin stripes. Thus, by combining single-unit recording with optical imaging and a computational approach, we identified RF subunits underlying spatial feature selectivity of V2 neurons and demonstrated the functional organization of these RF properties.

Expression profiling of the ubiquitin conjugating enzyme UbcM2 in murine brain reveals modest age-dependent decreases in specific neurons.

BackgroundUbcM2 is a ubiquitin-conjugating enzyme with roles in the turnover of damaged and misfolded proteins, cell cycle progression, development, and regulation of the antioxidant transcription factor, Nrf2. Recent screens have identified binding partners of the enzyme that are associated with various neurodegenerative diseases, and our previous studies have shown that UbcM2 is enriched in retina and brain.ResultsIn the current study, we characterized UbcM2 protein expression in various structures and cell types in the murine brain. Immunofluorescence analysis of paraffin-embedded brain sections revealed that UbcM2 is ubiquitously expressed throughout the brain, is enriched in hindbrain and cortex, and is robustly expressed in neurons. In contrast, the enzyme is undetectable in most astrocytes and microglia. As dysfunction of the ubiquitin proteasome system (UPS) has been linked to many age-related neurological diseases, we compared UbcM2 expression levels in young versus aged wild-type mice and found a global decrease in expression in aged brains, with reductions of 10 % or greater in five substructures (cerebellar granule cell layer, primary motor cortex, olfactory nucleus, superior colliculus, and secondary visual cortex).ConclusionsThese studies represent the first protein expression profiling of a ubiquitin-conjugating enzyme in the brain and support the notion that deficits in protein degradation and proteostasis associated with neurodegenerative diseases may be, in part, attributable to age-dependent reductions in the enzymatic machinery of the UPS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-015-0194-y) contains supplementary material, which is available to authorized users.