Axo-axonic synaptic input drives homeostatic plasticity by tuning the axon initial segment structurally and functionally.

Homeostatic plasticity maintains the stability of functional brain networks. The axon initial segment (AIS), where action potentials start, undergoes dynamic adjustment to exert powerful control over neuronal firing properties in response to network activity changes. However, it is poorly understood whether this plasticity involves direct synaptic input to the AIS.

Specific and Plastic: Chandelier Cell-to-Axon Initial Segment Connections in Shaping Functional Cortical Network.

Axon initial segment (AIS) is the most excitable subcellular domain of a neuron for action potential initiation. AISs of cortical projection neurons (PNs) receive GABAergic synaptic inputs primarily from chandelier cells (ChCs), which are believed to regulate action potential generation and modulate neuronal excitability. As individual ChCs often innervate hundreds of PNs, they may alter the activity of PN ensembles and even impact the entire neural network.

Axo-axonic synaptic input drives homeostatic plasticity by tuning the axon initial segment structurally and functionally.

Unlabelled: The stability of functional brain network is maintained by homeostatic plasticity, which restores equilibrium following perturbation. As the initiation site of action potentials, the axon initial segment (AIS) of glutamatergic projection neurons (PyNs) undergoes dynamic adjustment that exerts powerful control over neuronal firing properties in response to changes in network states. Although AIS plasticity has been reported to be coupled with the changes of network activity, it is poorly understood whether it involves direct synaptic input to the AIS.

Light-induced giant enhancement of nonreciprocal transport at KTaO-based interfaces.

Nonlinear transport is a unique functionality of noncentrosymmetric systems, which reflects profound physics, such as spin-orbit interaction, superconductivity and band geometry. However, it remains highly challenging to enhance the nonreciprocal transport for promising rectification devices. Here, we observe a light-induced giant enhancement of nonreciprocal transport at the superconducting and epitaxial CaZrO/KTaO (111) interfaces.

Whole-brain in vivo base editing reverses behavioral changes in Mef2c-mutant mice.

Whole-brain genome editing to correct single-base mutations and reduce or reverse behavioral changes in animal models of autism spectrum disorder (ASD) has not yet been achieved. We developed an apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-embedded cytosine base editor (AeCBE) system for converting C·G to T·A base pairs. We demonstrate its effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.

Controlled synthesis of transition metal oxide multi-shell structures andstudy of the energy storage mechanism.

Multi-shell transition metal oxide hollow spheres show great potential for applications in energy storage because of their unique multilayered hollow structure with large specific surface area, short electron and charge transport paths, and structural stability. In this paper, the controlled synthesis of NiCoO, MnCoO, NiMnOmulti-shell layer structures was achieved by using the solvothermal method. As the anode materials for Li-ion batteries, the three multi-shell structures maintained good stability after 650 long cycles in the cyclic charge/discharge test.

Anisotropic Amorphization and Phase Transition in Na Ti O Anode Caused by Electron Beam Irradiation.

Na Ti O is considered one of the most promising anode materials for sodium ion batteries due to its superior safety, environmental friendliness, and low manufacturing cost. However, its structural stability and reaction mechanism still have not been fully explored. As the electron beam irradiation introduces a similar impact on the Na Ti O anode as the extraction of Na ions during the battery discharge process, the microstructure evolution of the materials is investigated by advanced electron microscopy techniques at the atomic scale.

Projection-Specific Heterogeneity of the Axon Initial Segment of Pyramidal Neurons in the Prelimbic Cortex.

The axon initial segment (AIS) is a highly specialized axonal compartment where the action potential is initiated. The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons (PyNs), which likely contributes to their unique spiking properties. However, whether the various characteristics of AISs can be linked to specific PyN subtypes remains unknown.

TadA reprogramming to generate potent miniature base editors with high precision.

Although miniature CRISPR-Cas12f systems were recently developed, the editing efficacy and targeting range of derived miniature cytosine and adenine base editors (miniCBEs and miniABEs) have not been comprehensively addressed. Moreover, functional miniCBEs have not yet be established. Here we generate various Cas12f-derived miniCBEs and miniABEs with improved editing activities and diversified targeting scopes.

Distinct recruitment dynamics of chandelier cells and basket cells by thalamocortical inputs.

Diverse types of GABAergic interneurons tend to specialize in their inhibitory control of various aspects of cortical circuit operations. Among the most distinctive interneuron types, chandelier cells (i.e.

Oligophrenin-1 moderates behavioral responses to stress by regulating parvalbumin interneuron activity in the medial prefrontal cortex.

Ample evidence indicates that individuals with intellectual disability (ID) are at increased risk of developing stress-related behavioral problems and mood disorders, yet a mechanistic explanation for such a link remains largely elusive. Here, we focused on characterizing the syndromic ID gene oligophrenin-1 (OPHN1). We find that Ophn1 deficiency in mice markedly enhances helpless/depressive-like behavior in the face of repeated/uncontrollable stress.

Transcardiac Perfusion of the Mouse for Brain Tissue Dissection and Fixation.

Transcardiac perfusion with saline followed by 4% paraformaldehyde (PFA) is widely used to clear blood and preserve brain for immunostaining or hybridization. PFA breaks into formaldehyde in solution, which cross-link protein and DNA molecules to preserve tissue and cell structure. Here we provide a step by step guide for performing this procedure in mouse.

Axo-axonic Innervation of Neocortical Pyramidal Neurons by GABAergic Chandelier Cells Requires AnkyrinG-Associated L1CAM.

Among the diverse interneuron subtypes in the neocortex, chandelier cells (ChCs) are the only population that selectively innervate pyramidal neurons (PyNs) at their axon initial segment (AIS), the site of action potential initiation, allowing them to exert powerful control over PyN output. Yet, mechanisms underlying their subcellular innervation of PyN AISs are unknown. To identify molecular determinants of ChC/PyN AIS innervation, we performed an in vivo RNAi screen of PyN-expressed axonal cell adhesion molecules (CAMs) and select Ephs/ephrins.

Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain.

Throughout life, stem cells in the ventricular-subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts' morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain.

TRPC Channels and Neuron Development, Plasticity, and Activities.

In this chapter, we mainly focus on the functions of TRPC channels in brain development, including neural progenitor proliferation, neurogenesis, neuron survival, axon guidance, dendritic morphology, synaptogenesis, and neural plasticity. We also notice emerging advances in understanding the functions of TRPC channels in periphery, especially their functions in sensation and nociception in dorsal root ganglion (DRG). Because TRPC channels are expressed in all major types of glial cells, which account for at least half of total cells in the brain, TRPC channels may act as modulators for glial functions as well.

TRPC Channels in Health and Disease.

This chapter offers a brief introduction of the functions of TRPC channels in non-neuronal systems. We focus on three major organs of which the research on TRPC channels have been most focused on: kidney, heart, and lung. The chapter highlights on cellular functions and signaling pathways mediated by TRPC channels.

TGF-β/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis.

The mechanisms by which TGF-β promotes lung adenocarcinoma (ADC) metastasis are largely unknown. Here, we report that in lung ADC cells, TGF-β potently induces expression of DOCK4, but not other DOCK family members, via the Smad pathway and that DOCK4 induction mediates TGF-β's prometastatic effects by enhancing tumor cell extravasation. TGF-β-induced DOCK4 stimulates lung ADC cell protrusion, motility, and invasion without affecting epithelial-to-mesenchymal transition.

The X-linked mental retardation protein OPHN1 interacts with Homer1b/c to control spine endocytic zone positioning and expression of synaptic potentiation.

At glutamatergic synapses, local endocytic recycling of AMPA receptors (AMPARs) is important for the supply of a mobile pool of AMPARs required for synaptic potentiation. This local recycling of AMPARs critically relies on the presence of an endocytic zone (EZ) near the postsynaptic density (PSD). The precise mechanisms that couple the EZ to the PSD still remain largely elusive, with the large GTPase Dynamin-3 and the multimeric PSD adaptor protein Homer1 as the two main players identified.

Regulation of chandelier cell cartridge and bouton development via DOCK7-mediated ErbB4 activation.

Chandelier cells (ChCs), typified by their unique axonal morphology, are the most distinct interneurons present in cortical circuits. Via their distinctive axonal terminals, called cartridges, these cells selectively target the axon initial segment of pyramidal cells and control action potential initiation; however, the mechanisms that govern the characteristic ChC axonal structure have remained elusive. Here, by employing an in utero electroporation-based method that enables genetic labeling and manipulation of ChCs in vivo, we identify DOCK7, a member of the DOCK180 family, as a molecule essential for ChC cartridge and bouton development.

Canonical transient receptor potential 3 channels regulate mitochondrial calcium uptake.

Mitochondrial Ca(2+) homeostasis is fundamental to regulation of mitochondrial membrane potential, ATP production, and cellular Ca(2+) homeostasis. It has been known for decades that isolated mitochondria can take up Ca(2+) from the extramitochondrial solution, but the molecular identity of the Ca(2+) channels involved in this action is largely unknown. Here, we show that a fraction of canonical transient receptor potential 3 (TRPC3) channels is localized to mitochondria, a significant fraction of mitochondrial Ca(2+) uptake that relies on extramitochondrial Ca(2+) concentration is TRPC3-dependent, and the up- and down-regulation of TRPC3 expression in the cell influences the mitochondrial membrane potential.

Flufenamic acid promotes angiogenesis through AMPK activation.

Angiogenesis plays critical roles in development, tumor growth and metastasis. Flufenamic acid (FFA) is an anti-inflammatory agent known to alter ion fluxes across the plasma membrane. Its role in angiogenesis has not been fully addressed to date.

TRPC5 channel is the mediator of neurotrophin-3 in regulating dendritic growth via CaMKIIα in rat hippocampal neurons.

Neurotrophin-3 (NT-3) plays numerous important roles in the CNS and the elevation of intracellular Ca(2+) ([Ca(2+)](i)) is critical for these functions of NT-3. However, the mechanism by which NT-3 induces [Ca(2+)](i) elevation remains largely unknown. Here, we found that transient receptor potential canonical (TRPC) 5 protein and TrkC, the NT-3 receptor, exhibited a similar temporal expression in rat hippocampus and cellular colocalization in hippocampal neurons.

Target deletion of the cytoskeleton-associated protein palladin does not impair neurite outgrowth in mice.

Palladin is an actin cytoskeleton-associated protein which is crucial for cell morphogenesis and motility. Previous studies have shown that palladin is localized to the axonal growth cone in neurons and may play an important role in axonal extension. Previously, we have generated palladin knockout mice which display cranial neural tube closure defect and embryonic lethality before embryonic day 15.

Critical role of TRPC6 channels in VEGF-mediated angiogenesis.

Intracellular Ca(2+) signaling plays critical roles in VEGF-mediated angiogenesis. Transient receptor potential canonical (TRPC) channel 6, a Ca(2+)-permeable non-selective cation channel, can be activated by VEGF. Here, we report that TRPC6 is important for VEGF-mediated angiogenesis.

Functional roles of TRPC channels in the developing brain.

Transient receptor potential canonical (TRPC) channels are Ca(2+)-permeable, nonselective cation channels formed by homomeric or heteromeric complexes of TRPC proteins that contain six transmembrane domains. These channels can be activated through a phospholipase-C-dependent mechanism, making them sensors for environmental cues. Their expression begins early in embryonic days and remains in adulthood.