Changes in concentrations of NMDA receptor subunit GluN2B, Arc and syntaxin-1 in dorsal hippocampus Schaffer collateral synapses in a rat learned helplessness model of depression

Major depressive disorder involves changes in synaptic structure and function, but the molecular underpinnings of these changes are still not established. In an initial pilot experiment, whole-brain synaptosome screening with quantitative western blotting was performed to identify synaptic proteins that may show concentration changes in a congenital rat learned helplessness model of depression. We found that the N-methyl-D-aspartate receptor (NMDAR) subunits GluN2A/GluN2B, activityregulated cytoskeleton-associated protein (Arc) and syntaxin-1 showed significant concentration differences between congenitally learned helpless (LH) and nonlearned helpless (NLH) rats. Having identified these three proteins, we then performed more elaborate quantitative immunogold electron microscopic analyses of the proteins in a specific synapse type in the dorsal hippocampus: the Schaffer collateral synapse in the CA1 region. We expanded the setup to include also unstressed wild-type (WT) rats. The concentrations of the proteins in the LH and NLH groups were compared to WT animals. In this specific synapse, we found that the concentration of NMDARs was increased in postsynaptic spines in both LH and NLH rats. The concentration of Arc was significantly increased in postsynaptic densities in LH animals as well as in presynaptic cytoplasm of NLH rats. The concentration of syntaxin-1 was significantly increased in both presynaptic terminals and postsynaptic spines in LH animals, while pre- and postsynaptic syntaxin-1 concentrations were significantly decreased in NLH animals. These protein changes suggest pathways by which synaptic plasticity may be increased in dorsal hippocampal Schaffer collateral synapses during depression, corresponding to decreased synaptic stability.publishedVersio

Activity-regulated cytoskeletal-associated protein (Arc) in presynaptic terminals and extracellular vesicles in hippocampal synapses

The activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) is a neuron-specific immediate early gene (IEG) product. The protein regulates synaptic strength through modulation of spine density and morphology, AMPA receptor endocytosis, and as being part of a retrovirus-like inter-cellular communication mechanism. However, little is known about the detailed subsynaptic localization of the protein, and especially its possible presynaptic localization. In the present study, we provide novel electron microscopical data of Arc localization at hippocampal Schaffer collateral synapses in the CA1 region. The protein was found in both pre-and postsynaptic cytoplasm in a majority of synapses, associated with small vesicles. We also observed multivesicular body-like structures positive for Arc. Furthermore, the protein was located over the presynaptic active zone and the postsynaptic density. The relative concentration of Arc was 25% higher in the postsynaptic spine than in the presynaptic terminal. Notably, small extracellular vesicles labeled for Arc were detected in the synaptic cleft or close to the synapse, supporting a possible transsynaptic transmission of the protein in the brain

Brain Volume Changes after COVID-19 Compared to Healthy Controls by Artificial Intelligence-Based MRI Volumetry.

peer reviewedCohort studies that quantify volumetric brain data among individuals with different levels of COVID-19 severity are presently limited. It is still uncertain whether there exists a potential correlation between disease severity and the effects of COVID-19 on brain integrity. Our objective was to assess the potential impact of COVID-19 on measured brain volume in patients with asymptomatic/mild and severe disease after recovery from infection, compared with healthy controls, using artificial intelligence (AI)-based MRI volumetry. A total of 155 participants were prospectively enrolled in this IRB-approved analysis of three cohorts with a mild course of COVID-19 (n = 51, MILD), a severe hospitalised course (n = 48, SEV), and healthy controls (n = 56, CTL) all undergoing a standardised MRI protocol of the brain. Automated AI-based determination of various brain volumes in mL and calculation of normalised percentiles of brain volume was performed with mdbrain software, using a 3D T1-weighted magnetisation-prepared rapid gradient echo (MPRAGE) sequence. The automatically measured brain volumes and percentiles were analysed for differences between groups. The estimated influence of COVID-19 and demographic/clinical variables on brain volume was determined using multivariate analysis. There were statistically significant differences in measured brain volumes and percentiles of various brain regions among groups, even after the exclusion of patients undergoing intensive care, with significant volume reductions in COVID-19 patients, which increased with disease severity (SEV > MILD > CTL) and mainly affected the supratentorial grey matter, frontal and parietal lobes, and right thalamus. Severe COVID-19 infection, in addition to established demographic parameters such as age and sex, was a significant predictor of brain volume loss upon multivariate analysis. In conclusion, neocortical brain degeneration was detected in patients who had recovered from SARS-CoV-2 infection compared to healthy controls, worsening with greater initial COVID-19 severity and mainly affecting the fronto-parietal brain and right thalamus, regardless of ICU treatment. This suggests a direct link between COVID-19 infection and subsequent brain atrophy, which may have major implications for clinical management and future cognitive rehabilitation strategies

Changes in synaptic proteins in hippocampal area CA1 of a rat learned helpless model of depression

Major depressive disorder (MDD) is one of the most common mood disorders in the world with a life-time prevalence of approximately 17%. MDD is characterized by emotional and cognitive disturbances, and is accompanied by volumetric changes of neural areas that likely arise from disturbed forms of neuroplasticity. The hippocampus has received a wealth of attention in MDD-related research not only because it is a prominent area to study forms of neuroplasticity, but also because it is engaged in cognitive as well as in emotional functions. In addition, the hippocampus displays a volumetric decrease in MDD. While it has been shown that stress associated with the development of MDD modulates forms of synaptic plasticity, investigations into the molecular correlates of these plastic changes are negligible. The present work investigates the immunolocalization and concentration of synaptic proteins involved in synaptic plasticity in the learned helpless model of depression. By means of immunogold electron microscopy, the relative concentration of the synaptic proteins syntaxin1, the NMDA receptor subunit NR2B, and Arc were examined in different region of the synapse. The synaptic regions of interest were the active zone, the postsynaptic density (PSD), and the presynaptic and postsynaptic cytoplasm in Schaffer collateral synapses of hippocampal area CA1. Comparing the learned helpless group to the wild-type group, I found a higher concentration of NR2B in the postsynaptic cytoplasm and in the PSD, as well as a higher concentration of Arc in the PSD of the learned helpless group. By contrasting the non-learned helpless group to the wild-type group, I found a lower concentration of syntaxin1 in both the presynaptic cytoplasm and in the PSD, as well as a greater concentration of NR2B in the postsynaptic cytoplasm and in the PSD in the non-learned helpless group. In addition, the learned helpless group displayed a higher concentration of syntaxin1 in the pre- and postsynaptic cytoplasm compared to the non-learned helpless group. The altered relative concentrations of these proteins are probably related to changes in synaptic plasticity in the learned helpless model of depression. One may speculate that the changed relative concentrations of the synaptic proteins contribute to the behavioral changes in the learned helpless model, and hence may be related to the pathology of MDD

Visual short-term memory always requires general attention

Data from "Visual short-term memory always requires general attention" by C. Morey and M. Bieler, published in Psychonomic Bulletin and Review, 2013. The analyses enclosed support a talk given by C. Morey at the meeting of the European Society for Cognitive Psychology in Paphos, Cyprus, September 2015. For open-access author final version, see C. Morey's institutional website: http://www.ppls.ed.ac.uk/people/candice-morey Publisher link: http://link.springer.com/article/10.3758%2Fs13423-012-0313-

Cross-Talk of Low-Level Sensory and High-Level Cognitive Processing: Development, Mechanisms, and Relevance for Cross-Modal Abilities of the Brain

The emergence of cross-modal learning capabilities requires the interaction of neural areas accounting for sensory and cognitive processing. Convergence of multiple sensory inputs is observed in low-level sensory cortices including primary somatosensory (S1), visual (V1), and auditory cortex (A1), as well as in high-level areas such as prefrontal cortex (PFC). Evidence shows that local neural activity and functional connectivity between sensory cortices participate in cross-modal processing. However, little is known about the functional interplay between neural areas underlying sensory and cognitive processing required for cross-modal learning capabilities across life. Here we review our current knowledge on the interdependence of low- and high-level cortices for the emergence of cross-modal processing in rodents. First, we summarize the mechanisms underlying the integration of multiple senses and how cross-modal processing in primary sensory cortices might be modified by top-down modulation of the PFC. Second, we examine the critical factors and developmental mechanisms that account for the interaction between neuronal networks involved in sensory and cognitive processing. Finally, we discuss the applicability and relevance of cross-modal processing for brain-inspired intelligent robotics. An in-depth understanding of the factors and mechanisms controlling cross-modal processing might inspire the refinement of robotic systems by better mimicking neural computations

Changes in concentrations of NMDA receptor subunit GluN2B, Arc and syntaxin-1 in dorsal hippocampus Schaffer collateral synapses in a rat learned helplessness model of depression

Major depressive disorder involves changes in synaptic structure and function, but the molecular underpinnings of these changes are still not established. In an initial pilot experiment, whole-brain synaptosome screening with quantitative western blotting was performed to identify synaptic proteins that may show concentration changes in a congenital rat learned helplessness model of depression. We found that the N-methyl-D-aspartate receptor (NMDAR) subunits GluN2A/GluN2B, activityregulated cytoskeleton-associated protein (Arc) and syntaxin-1 showed significant concentration differences between congenitally learned helpless (LH) and nonlearned helpless (NLH) rats. Having identified these three proteins, we then performed more elaborate quantitative immunogold electron microscopic analyses of the proteins in a specific synapse type in the dorsal hippocampus: the Schaffer collateral synapse in the CA1 region. We expanded the setup to include also unstressed wild-type (WT) rats. The concentrations of the proteins in the LH and NLH groups were compared to WT animals. In this specific synapse, we found that the concentration of NMDARs was increased in postsynaptic spines in both LH and NLH rats. The concentration of Arc was significantly increased in postsynaptic densities in LH animals as well as in presynaptic cytoplasm of NLH rats. The concentration of syntaxin-1 was significantly increased in both presynaptic terminals and postsynaptic spines in LH animals, while pre- and postsynaptic syntaxin-1 concentrations were significantly decreased in NLH animals. These protein changes suggest pathways by which synaptic plasticity may be increased in dorsal hippocampal Schaffer collateral synapses during depression, corresponding to decreased synaptic stability

Neonatal Restriction of Tactile Inputs Leads to Long-Lasting Impairments of Cross-Modal Processing

<div><p>Optimal behavior relies on the combination of inputs from multiple senses through complex interactions within neocortical networks. The ontogeny of this multisensory interplay is still unknown. Here, we identify critical factors that control the development of visual-tactile processing by combining in vivo electrophysiology with anatomical/functional assessment of cortico-cortical communication and behavioral investigation of pigmented rats. We demonstrate that the transient reduction of unimodal (tactile) inputs during a short period of neonatal development prior to the first cross-modal experience affects feed-forward subcortico-cortical interactions by attenuating the cross-modal enhancement of evoked responses in the adult primary somatosensory cortex. Moreover, the neonatal manipulation alters cortico-cortical interactions by decreasing the cross-modal synchrony and directionality in line with the sparsification of direct projections between primary somatosensory and visual cortices. At the behavioral level, these functional and structural deficits resulted in lower cross-modal matching abilities. Thus, neonatal unimodal experience during defined developmental stages is necessary for setting up the neuronal networks of multisensory processing.</p></div