Biology subjects

Acsady, L.

Publications and source records attributed to Acsady, L..

5 recordsLinked to original sources

bioRxiv2023

A cortico-subcortical loop for motor control via the pontine reticular formation

Movement and locomotion are controlled by large neuronal circuits like the cortex-basal ganglia (BG)-thalamus loop. Inhibitory output of the BG loop can directly control movement via specialized connections with the brainstem. Whether other parallel loops with similar logic exist is presently unclear. Here we demonstrate that glycine transporter 2-positive (GlyT2+) cells of the pontine reticular formation (PRF) receive cortical inputs and in turn innervate the thalamus. Thalamus-projecting GlyT2+ cells innervate subcortical regions distinct from BG targets. Cortical cells co-innervate PRF/GlyT2+ cells and thalamus as in the BG loops. Cortex exerts strong excitatory control on PRF/GlyT2+ cells and these neurons powerfully inhibit their thalamic targets. Activation of thalamus projecting PRF/GlyT2+ cells leads to contralateral turning. These results demonstrate that the PRF is part of a cortico-subcortical loop that regulates motor activity parallel to the BG circuits. The cortico-PRF-thalamus loop can synergistically control turning with the BG loops via distinct descending pathways. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=190 HEIGHT=200 SRC="FIGDIR/small/552594v2_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@fa1ed8org.highwire.dtl.DTLVardef@ff110dorg.highwire.dtl.DTLVardef@1b88ed7org.highwire.dtl.DTLVardef@1aa02a8_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Infection-induced vascular inflammation in COVID-19 links focal microglial dysfunction with neuropathologies through IL-1/IL-6-related systemic inflammatory states

COVID-19 is associated with diverse neurological abnormalities, which predict poor outcome in patients. However, the mechanisms whereby infection-induced inflammation could affect complex neuropathologies in COVID-19 are unclear. We hypothesized that microglia, the resident immune cells of brain, are centrally involved in this process. To study this, we developed an autopsy platform allowing the integration of molecular anatomy-, protein- and mRNA data sets in post-mortem mirror blocks of brain and peripheral organ samples from COVID-19 cases. Nanoscale microscopy, single-cell RNA sequencing and analysis of inflammatory and metabolic signatures revealed distinct mechanisms of microglial dysfunction associated with cerebral SARS-CoV-2 infection. We observed focal loss of microglial P2Y12R at sites of virus-associated vascular inflammation together with dysregulated microglia-vascular-astrocyte interactions, Cx3Cr1-fractalkine axis deficits and mitochondrial failure in severely affected medullary autonomic nuclei and other brain areas. Microglial dysfunction occurs at sites of excessive synapse- and myelin phagocytosis and loss of glutamatergic terminals. While central and systemic viral load is strongly linked in individual patients, the regionally heterogenous microglial reactivity in the brain correlated with the extent of central and systemic inflammation related to IL-1 / IL-6 via virus-sensing pattern recognition receptors (PRRs) and inflammasome activation pathways. Thus, SARS-CoV-2-induced central and systemic inflammation might lead to a primarily glio-vascular failure in the brain, which could be a common contributor to diverse COVID-19-related neuropathologies.

immunology↗

bioRxiv2023

An image segmentation method based on the spatial correlation coefficient of Local Moran's I

Unsupervised segmentation in biological and non-biological images is only partially resolved. Segmentation either requires arbitrary thresholds or large teaching datasets. Here we propose a spatial autocorrelation method based on Local Morans I coefficient to differentiate signal, background and noise in any type of image. The method, originally described for geoinformatics, does not require a predefined intensity threshold or teaching algorithm for image segmentation and allows quantitative comparison of samples obtained in different conditions. It utilizes relative intensity as well as spatial information of neighboring elements to select spatially contiguous groups of pixels. We demonstrate that Morans method outperforms threshold-based method (TBM) in both artificially generated as well as in natural images especially when background noise is substantial. This superior performance can be attributed to the exclusion of false positive pixels resulting from isolated, high intensity pixels in high noise conditions. To test the methods power in real situation we used high power confocal images of the somatosensory thalamus immunostained for Kv4.2 and Kv4.3 (A-type) voltage gated potassium channels. Morans method identified high intensity Kv4.2 and Kv4.3 ion channel clusters in the thalamic neuropil. Spatial distribution of these clusters displayed strong correlation with large sensory axon terminals of subcortical origin. The unique association of the special presynaptic terminals and a postsynaptic voltage gated ion channel cluster was confirmed with electron microscopy. These data demonstrate that Morans method is a rapid, simple image segmentation method optimal for variable and high nose conditions.

bioinformatics↗

bioRxiv2023

Persistently increased post-stress activity of paraventricular thalamic neurons is essential for the emergence of stress-induced maladaptive behavior

ABSTRACTTraumatic events can immediately lead to debilitating symptoms collectively called Acute Stress Disorder (ASD), however the mechanisms of ASD are poorly understood. Using a rodent model of ASD here we identify a crucial communication bottleneck between the brainstem and the forebrain, the calretinin-positive neurons in the paraventricular thalamus (PVT/CR+), that controls ASD. We show that following a single acute stress event, the pre-sleep behavior of the mice is altered for several days in parallel with a persistent increase in the firing rate of PVT/CR+ cells. Optogenetic inhibition of PVT/CR+ neuronal activity after the stress event for one hour was sufficient to rescue both the ASD symptoms and the prolonged increase in PVT/CR+ firing rate. Inhibition applied 5 days later was still able to ameliorate some of the symptoms. These data suggest that post-stress activity of PVT/CR+ neurons play a critical role in mediating the acute forms of stress-related affective dysfunctions. One-Sentence SummaryPost-stress inhibition of paraventricular thalamic neurons prevents the emergence of acute stressed phenotype.

neuroscience↗

bioRxiv2022

Region Selective Cortical Control Of The Thalamic Reticular Nucleus

Corticothalamic pathways, responsible for the top-down control of the thalamus display a classical, canonical organization in that every cortical region sends dual, layer 6 (L6) and layer 5 (L5) output to the thalamus. Here we demonstrate a qualitative, region-specific difference in the organization of corticothalamic pathways. We show that L5 pyramidal cells of the frontal, but not other cortical regions establish monosynaptic connection with the inhibitory thalamic reticular nucleus (TRN). The frontal L5-TRN pathway paralleled the L6-TRN projection but displayed distinct morphological and physiological features. The exact spike output of the L5 contacted TRN cells correlated with the level of cortical synchrony. Optogenetic perturbation of the L5-TRN connection disrupted the tight link between cortical and TRN activity. L5-driven TRN cells innervated all thalamic nuclei involved in the control of frontal cortical activity. Our data show that frontal cortical functions require a highly specialized cortical control over intrathalamic inhibitory processes.

neuroscience↗