Biology subjects

Nusser, Z.

Publications and source records attributed to Nusser, Z..

5 recordsLinked to original sources

bioRxiv2024

Diverse calcium dynamics underlie place field formation in hippocampal CA1 pyramidal cells

Every explored environment is represented in the hippocampus by the activity of distinct populations of pyramidal cells (PCs) that typically fire at specific locations called their place fields (PFs). New PFs are constantly born even in familiar surroundings (during representational drift), and many rapidly emerge when the animal explores a new or altered environment (during global or partial remapping). Behavioral time scale synaptic plasticity (BTSP), a plasticity mechanism based on prolonged somatic action potential (AP) bursts induced by dendritic Ca2+/NMDA plateau potentials, was recently proposed as the main cellular mechanism underlying new PF formations (PFF), but it is unclear whether burst-associated large somatic [Ca2+] transients are always necessary and/or sufficient for PFF. To address this issue, here we performed in vivo two-photon [Ca2+] imaging of hippocampal CA1 PCs in head-restrained mice to investigate somatic [Ca2+] dynamics underlying PFFs in familiar and novel virtual environments. Our results demonstrate that although many PFs are formed by BTSP-like events, PFs also emerge with initial [Ca2+] dynamics that do not match any of the characteristics of BTSP. BTSP and non-BTSP-like new PFFs occur spontaneously in familiar environments, during neuronal representational switches and instantaneously in new environments. Our data also reveal that solitary [Ca2+] transients with larger amplitudes than those evoking BTSP-like PFFs, frequently occur without inducing PFs, demonstrating that large [Ca2+] transients per se are not sufficient for PFF.

neuroscience↗

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↗

bioRxiv2021

Diversity of excitatory release sites

The molecular mechanisms underlying the diversity of cortical glutamatergic synapses is still only partially understood. Here, we tested the hypothesis that presynaptic active zones (AZs) are constructed from molecularly uniform, independent release sites (RSs), the number of which scales linearly with the AZ size. Paired recordings between hippocampal CA1 pyramidal cells and fast-spiking interneurons followed by quantal analysis demonstrate large variability in the number of RSs (N) at these connections. High resolution molecular analysis of functionally characterized synapses reveals highly variable Munc13-1 content of AZs that possess the same N. Replica immunolabeling also shows a 3-fold variability in the Munc13-1 content of AZs of identical size. Munc13-1 is clustered within the AZs; cluster size and density are also variable. Our results provide evidence for quantitative molecular heterogeneity of RSs and support a model in which the AZ is built up from variable numbers of molecularly heterogeneous, but independent RSs.

neuroscience↗

bioRxiv2019

Functional specification of CCK+ interneurons by alternative isoforms of Kv4.3 auxiliary subunits

CCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity. We found two firing phenotypes of CCK+INs in rat CA3 area; either possessing a previously undetected membrane potential-dependent firing or regular firing phenotype, due to different low-voltage-activated potassium currents. These different excitability properties destine the two types for distinct functions, because the former is essentially silenced during realistic 8-15 Hz oscillations. The general excitability, morphology and gene-profiles of the two types were surprisingly similar. Even the expression of Kv4.3 channels were comparable, despite evidences showing that Kv4.3-mediated currents underlie the distinct firing properties. Instead, the firing phenotypes were correlated with the presence of distinct isoforms of Kv4 auxiliary subunits (KChIP1 vs. KChIP4e and DPP6S). Our results reveal the underlying mechanisms of two previously unknown types of CCK+INs and demonstrate that alternative splicing of few genes, which may be viewed as a minor event in the cells whole transcriptome, can underlie distinct cell-type identity.

neuroscience↗

bioRxiv2018

Distinct nanoscale calcium channel and synaptic vesicle topographies contribute to the diversity of synaptic function

The nanoscale topographical arrangement of voltage-gated calcium channels (VGCC) and synaptic vesicles (SVs) determines synaptic strength and plasticity, but whether distinct spatial distributions underpin diversity of synaptic function is unknown. We performed single bouton Ca2+ imaging, Ca2+ chelator competition, immunogold electron microscopic (EM) localization of VGCCs and the active zone (AZ) protein Munc13-1, at two cerebellar synapses. Unexpectedly, we found that weak synapses exhibited 3-fold more VGCCs than strong synapses, while the coupling distance was 5-fold longer. Reaction-diffusion modelling could explain both functional and structural data with two strikingly different nanotopographical motifs: strong synapses are composed of SVs that are tightly coupled ([~]10 nm) to VGCC clusters, whereas at weak synapses VGCCs were excluded from the vicinity ([~]50 nm) of docked vesicles. The distinct VGCC-SV topographical motifs also confer differential sensitivity to neuromodulation. Thus VGCC-SV arrangements are not canonical across CNS synapses and their diversity could underlie functional heterogeneity.

neuroscience↗