Biology subjects

Kruessel, S.

Publications and source records attributed to Kruessel, S..

5 recordsLinked to original sources

bioRxiv2025

Intercellular communication in the brain via dendritic nanotubular network

Recent studies have identified intercellular networks for material exchange by bridge-like nanotubular structures, yet their existence in neurons remains unexplored within the brain. Here, we identified long, thin dendritic filopodia that establish direct dendrite-to-dendrite contacts, forming dendritic nanotubes (DNTs) in mammalian brains. Using super-resolution microscopy, we characterized their unique molecular composition and dynamics in dissociated neurons, enabling Ca2+ propagation over distances. Utilizing imaging and machine-learning-based analysis, we confirmed the in situ presence of DNTs connecting dendrites to other dendrites whose anatomical features are distinguished from synaptic dendritic spines. DNTs mediate the active transport of small molecules or human amyloid-beta (A{beta}), implicating the role of DNT network in AD pathology. Notably, DNT levels increased prior to the onset of amyloid plaque deposits in the mPFC of APP/PS1 mice. Computational simulations predicted the progression of amyloidosis, providing insight into the mechanisms underlying neurodegeneration through these DNTs. This study unveils a previously unrecognized nanotubular network, highlighting another dimension of neuronal connectivity beyond synapses.

neuroscience↗

bioRxiv2023

Exuberant de novo dendritic spine growth in mature neurons

Dendritic spines are structural correlates of excitatory synapses maintaining stable synaptic communications. However, this strong spine-synapse relationship was mainly characterized in excitatory pyramidal neurons (PyNs), raising a possibility that inferring synaptic density from dendritic spine number may not be universally applied to all neuronal types. Here we found that the ectopic expression of H-Ras increased dendritic spine numbers regardless of cortical cell types such as layer 2/3 pyramidal neurons (PyNs), parvalbumin (PV)- and vasoactive intestinal peptide (VIP)-positive interneurons (INs) in the primary motor cortex (M1). The probability of detecting dendritic spines was positively correlated with the magnitude of H-Ras activity, suggesting elevated local H-Ras activity is involved in the process of dendritic spine formation. H-Ras overexpression caused high spine turnover rate via adding more spines rather than eliminating them. Two-photon photolysis of glutamate triggered de novo dendritic spine formation in mature neurons, suggesting H-Ras induced spine formation is not restricted to the early development. In PyNs and PV-INs, but not VIP-INs, we observed a shift in average spine neck length towards longer filopodia-like phenotypes. The portion of dendritic spines lacking key excitatory synaptic proteins were significantly increased in H-Ras transfected neurons, suggesting that these increased spines have other distinct functions. High spine density caused by H-Ras did not result in change in the frequency or the amplitude of miniature excitatory postsynaptic currents (mEPSCs). Thus, our results propose that dendritic spines possess more multifaceted functions beyond the morphological proxy of excitatory synapse.

neuroscience↗

bioRxiv2023

VAP spatially stabilizes dendritic mitochondria to locally fuel synaptic plasticity

Synapses are pivotal sites of memory formation and undergo plasticity in response to external inputs. Consequently, synapses are hotspots of energy consumption and are susceptible to dysfunction when their energy supplies are perturbed. Mitochondria are stabilized near synapses via cytoskeletal tethering and serve as local energy supplies to fuel synaptic plasticity. However, the mechanisms that tether and stabilize neuronal mitochondria for long durations and determine the spatial dendritic segment supported during synaptic plasticity are unknown. We identified a list of novel mitochondrial-cytoskeletal interactors in neurons using APEX-based proximity labeling. We narrowed down the protein candidates that exclusively tether mitochondria to actin near postsynaptic spines using high-resolution Airyscan confocal imaging. We find that VAP, the vesicle-associated membrane protein-associated protein implicated in Amyotrophic Lateral Sclerosis and interacts with the endoplasmic reticulum, stabilizes mitochondria via actin near the spines. To test if the VAP-dependent stable mitochondrial compartments can locally support synaptic plasticity, we investigated individual spines stimulated by two-photon glutamate uncaging for spine plasticity induction and their adjacent spines. We find that, along with actin, VAP functions as a spatial stabilizer of mitochondrial compartments to sustain synaptic plasticity for up to ~60 min and as a spatial ruler that determines the ~30 m length of the dendritic segment supporting synaptic plasticity.

neuroscience↗

bioRxiv2021

Tagging active neurons by soma-targeted Cal-Light

Verifying causal effects of neural circuits is essential for proving direct a circuit-behavior relationship. However, techniques for tagging only active neurons with high spatiotemporal precision remain at the beginning stages. Here we developed the soma-targeted Cal-Light (ST-Cal-Light) which selectively converts somatic calcium rise triggered by action potentials into gene expression. Such modification simultaneously increases the signal-to-noise ratio (SNR) of reporter gene expression and reduces the light requirement for successful labeling. Because of the enhanced efficacy, the ST-Cal-Light enables the tagging of functionally engaged neurons in various forms of behaviors, including context-dependent fear conditioning, leverpressing choice behavior, and social interaction behaviors. We also targeted kainic acid-sensitive neuronal populations in the hippocampus which subsequently suppressed seizure symptoms, suggesting ST-Cal-Lights applicability in controlling disease-related neurons. Furthermore, the generation of a conditional ST-Cal-Light knock-in (KI) mouse provides an opportunity to tag active neurons in a region- or cell-type specific manner via crossing with other Cre-driver lines. Thus, the versatile ST-Cal-Light system links somatic action potentials to behaviors with high temporal precision, and ultimately allows functional circuit dissection at a single cell resolution.

neuroscience↗

bioRxiv2020

Development of a genetically-encoded oxytocin sensor

Oxytocin (OXT) is a neuropeptide originating in the paraventricular nucleus (PVN) of the hypothalamus, with a role in influencing various social behaviors. However, pinpointing its actions only during the time animals are performing specific behaviors has been difficult to study. Here we developed an optogenetic gene expression system designed to selectively label neuronal populations activated by OXT in the presence of blue-light, named "OXTR-iTango2". The OXTR-iTango2 was capable of inducing gene expression of a reporter gene in both human embryonic kidney (HEK) cells and neurons in a quantitative manner. In vivo expression of OXTR-iTango2 selectively labeled OXT-sensitive neurons in a blue-light dependent manner. Furthermore, we were able to detect a subset of dopamine (DA) neurons in the ventral tegmental area (VTA) that receive OXT activation during social interaction. Thus, we provide a genetically-encoded, scalable optogenetic toolset to target neural circuits activated by OXT in behaving animals with a high temporal resolution.

neuroscience↗