Basal forebrain activation enhances between-trial reliability of low-frequency local field potentials (LFP) and spiking activity in tree shrew primary visual cortex (V1)

Brain state has profound effects on neural processing and stimulus encoding in sensory cortices. While the synchronized state is dominated by low-frequency local field potential (LFP) activity, low-frequency LFP power is suppressed in the desynchronized state, where a concurrent enhancement in gamma power is observed. Recently, it has been shown that cortical desynchronization co-occurs with enhanced between-trial reliability of spiking activity in sensory neurons, but it is currently unclear whether this effect is also evident in LFP signals. Here, we address this question by recording both spike trains and LFP in primary visual cortex during natural movie stimulation, and using isoflurane anesthesia and basal forebrain (BF) electrical activation as proxies for synchronized and desynchronized brain states. We show that indeed, low-frequency LFP modulations (“LFP events”) also occur more reliably following BF activation. Interestingly, while being more reliable, these LFP events are smaller in amplitude compared to those generated in the synchronized brain state. We further demonstrate that differences in reliability of spiking activity between cortical states can be linked to amplitude and probability of LFP events. The correlated temporal dynamics between low-frequency LFP and spiking response reliability in visual cortex suggests that these effects may both be the result of the same neural circuit activation triggered by BF stimulation, which facilitates switching between processing of incoming sensory information in the desynchronized and reverberation of internal signals in the synchronized state

On the Relation Between Receptive Field Structure and Stimulus Selectivity in the Tree Shrew Primary Visual Cortex

There are notable differences in functional properties of primary visual cortex (V1) neurons among mammalian species, particularly those concerning the occurrence of simple and complex cells and the generation of orientation selectivity. Here, we present quantitative data on receptive field (RF) structure, response modulation, and orientation tuning for single neurons in V1 of the tree shrew, a close relative of primates. We find that spatial RF subfield segregation, a criterion for identifying simple cells, was exceedingly small in the tree shrew V1. In contrast, many neurons exhibited elevated F1/F0 modulation that is often used as a simple cell marker. This apparent discrepancy can be explained by the robust stimulus polarity preference in tree shrew V1, which inflates F1/F0 ratio values. RF structure mapped with sparse-noise—which is spatially restricted and emphasizes thalamo-cortical feed-forward inputs—appeared unrelated to orientation selectivity. However, RF structure mapped using the Hartley subspace stimulus—which covers a large area of the visual field and recruits considerable intracortical processing—did predict orientation preference. Our findings reveal a number of striking similarities in V1 functional organization between tree shrews and primates, emphasizing the important role of intracortical recurrent processing in shaping V1 response properties in these specie

Reduced pain perception in children and adolescents with ADHD is normalized by methylphenidate

Background: The present study examined pain perception in children and adolescents with ADHD and the interaction between pain perception and the administration of methylphenidate (MPH) in order to generate hypotheses for further research that will help to clarify the association between ADHD diagnosis, MPH treatment and pain perception. Methods: We included 260 children and adolescents of the “German Health Interview and Examination Survey for Children and Adolescents” (KiGGS) and analyzed parent’s assessments of children’s pain distribution and pain perception, as well as the influence of MPH administration on pain perception in affected children and adolescents. Results: Pain perception was associated with ADHD and MPH administration, indicating that children and adolescents suffering from ADHD without MPH treatment were reported to have lower pain perception compared to both, healthy controls (HC) and ADHD patients medicated with MPH. Conclusion: We suggest that reduced pain perception in children and adolescents with ADHD not medicated with MPH may lead to higher risk tolerance by misjudgments of dangerous situations, expanding the importance of MPH administration in affected children and adolescents

Processing of the Terminal Alpha-1,2-Linked Mannose Residues From Oligomannosidic N-Glycans Is Critical for Proper Root Growth

N-glycosylation is an essential protein modification that plays roles in many diverse biological processes including protein folding, quality control and protein interactions. Despite recent advances in characterization of the N-glycosylation and N-glycan processing machinery our understanding of N-glycosylation related processes in plant development is limited. In Arabidopsis thaliana, failure of mannose trimming from oligomannosidic N-glycans in the endoplasmic reticulum (ER) and cis/medial-Golgi leads to a defect in root development in the mns123 triple mutant. Here, we show that the severe root phenotype of mns123 is restored in asparagine-linked glycosylation (ALG)-deficient plants with distinct defects in the biosynthesis of the lipid-linked oligosaccharide precursor. The root growth of these ALG-deficient plants is not affected by the α-mannosidase inhibitor kifunensine. Genetic evidence shows that the defect is uncoupled from the glycan-dependent ER-associated degradation (ERAD) pathway that removes misfolded glycoproteins with oligomannosidic N-glycans from the ER. Restoration of mannose trimming using a trans-Golgi targeted α-mannosidase suppresses the defect of mns123 roots. These data suggest that processing of terminal mannose residues from oligomannosidic N-glycans is important for an unknown late-Golgi or post-Golgi process that is implicated in proper root formation

A Comprehensive Optogenetic Pharmacology Toolkit for In Vivo Control of GABAA Receptors and Synaptic Inhibition

SummaryExogenously expressed opsins are valuable tools for optogenetic control of neurons in circuits. A deeper understanding of neural function can be gained by bringing control to endogenous neurotransmitter receptors that mediate synaptic transmission. Here we introduce a comprehensive optogenetic toolkit for controlling GABAA receptor-mediated inhibition in the brain. We developed a series of photoswitch ligands and the complementary genetically modified GABAA receptor subunits. By conjugating the two components, we generated light-sensitive versions of the entire GABAA receptor family. We validated these light-sensitive receptors for applications across a broad range of spatial scales, from subcellular receptor mapping to in vivo photo-control of visual responses in the cerebral cortex. Finally, we generated a knockin mouse in which the “photoswitch-ready” version of a GABAA receptor subunit genomically replaces its wild-type counterpart, ensuring normal receptor expression. This optogenetic pharmacology toolkit allows scalable interrogation of endogenous GABAA receptor function with high spatial, temporal, and biochemical precision

Expression of submaxillary gland androgen-regulated protein 3A (SMR3A) in adenoid cystic carcinoma of the head and neck

Background: Adenoid cystic carcinoma of the head and neck (ACC) is a rare tumor entity which originates from the salivary glands. The prognosis remains poor, as the tumor tends to exhibit perineural invasion and frequently develops distant metastases. The submaxillary gland androgen-regulated protein 3A (SMR3A) belongs to a gene family producing opiorphin homologs and is physiologically secreted by salivary glands. Expression of SMR3A has been identified as an unfavorable risk factor in survival of patients with squamous cell carcinoma in the head and neck, but its value as a prognostic biomarker for ACC has not been addressed. Materials and Methods: Tissue sections from primary ACC (n=86) and healthy glandular tissue as reference, were stained by immunohistochemistry. SMR3A expression levels were correlated with clinical and pathological features, including overall survival. Results: All patients had undergone surgery and 67 received adjuvant radiotherapy. The median disease-free survival (DFS) was 37 months and the median overall survival (OS) was 75 months. Prominent SMR3A expression in tumor cells was found in 24 of 86 patients (27,9%), and was inversely correlated with a male gender (p=0.009). There was no significant correlation between SMR3A expression and DFS, metastasis-free survival or OS. Conclusion: Our data demonstrate for the first time decreased levels of SMR3A in ACC compared to normal glandular tissue. These data suggest a context-dependent regulation of SMR3A expression in the pathogenesis of distinct subtypes of head and neck tumors, and support the assumption that detection of SMR3A expression serves as a surrogate for aberrant differentiation into mucosal- or glandular-like cells in ACC and head and neck squamous cell carcinoma