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Neuroscience Bulletin Nov 2023Epilepsy is a common, chronic neurological disorder that has been associated with impaired neurodevelopment and immunity. The chemokine receptor CXCR5 is involved in...
Epilepsy is a common, chronic neurological disorder that has been associated with impaired neurodevelopment and immunity. The chemokine receptor CXCR5 is involved in seizures via an unknown mechanism. Here, we first determined the expression pattern and distribution of the CXCR5 gene in the mouse brain during different stages of development and the brain tissue of patients with epilepsy. Subsequently, we found that the knockdown of CXCR5 increased the susceptibility of mice to pentylenetetrazol- and kainic acid-induced seizures, whereas CXCR5 overexpression had the opposite effect. CXCR5 knockdown in mouse embryos via viral vector electrotransfer negatively influenced the motility and multipolar-to-bipolar transition of migratory neurons. Using a human-derived induced an in vitro multipotential stem cell neurodevelopmental model, we determined that CXCR5 regulates neuronal migration and polarization by stabilizing the actin cytoskeleton during various stages of neurodevelopment. Electrophysiological experiments demonstrated that the knockdown of CXCR5 induced neuronal hyperexcitability, resulting in an increased number of seizures. Finally, our results suggested that CXCR5 deficiency triggers seizure-related electrical activity through a previously unknown mechanism, namely, the disruption of neuronal polarity.
Topics: Animals; Humans; Mice; Actin Cytoskeleton; Actins; Epilepsy; Neurons; Receptors, CXCR5; Seizures
PubMed: 37460877
DOI: 10.1007/s12264-023-01087-w -
ENeuro Jun 2023The fruit fly has provided important insights into how sensory information is transduced by transient receptor potential (TRP) channels in the peripheral nervous system...
The fruit fly has provided important insights into how sensory information is transduced by transient receptor potential (TRP) channels in the peripheral nervous system (PNS). However, TRP channels alone have not been able to completely model mechanosensitive transduction in mechanoreceptive chordotonal neurons (CNs). Here, we show that, in addition to TRP channels, the sole voltage-gated sodium channel (Na) in , Para, is localized to the dendrites of CNs. Para is localized to the distal tip of the dendrites in all CNs, from embryos to adults, and is colocalized with the mechanosensitive TRP channels No mechanoreceptor potential C (NompC) and Inactive/Nanchung (Iav/Nan). Para localization also demarcates spike initiation zones (SIZs) in axons and the dendritic localization of Para is indicative of a likely dendritic SIZ in fly CNs. Para is not present in the dendrites of other peripheral sensory neurons. In both multipolar and bipolar neurons in the PNS, Para is present in a proximal region of the axon, comparable to the axonal initial segment (AIS) in vertebrates, 40-60 μm from the soma in multipolar neurons and 20-40 μm in bipolar neurons. Whole-cell reduction of expression using RNAi in CNs of the adult Johnston's organ (JO) severely affects sound-evoked potentials (SEPs). However, the duality of Para localization in the CN dendrites and axons identifies a need to develop resources to study compartment-specific roles of proteins that will enable us to better understand Para's role in mechanosensitive transduction.
Topics: Animals; Action Potentials; Axons; Dendrites; Drosophila; Drosophila melanogaster; Sensory Receptor Cells; Transient Receptor Potential Channels; Voltage-Gated Sodium Channels
PubMed: 37328295
DOI: 10.1523/ENEURO.0105-23.2023 -
The Korean Journal of Physiology &... Mar 2024The slow and regular pacemaking activity of midbrain dopamine (DA) neurons requires proper spatial organization of the excitable elements between the soma and dendritic...
The slow and regular pacemaking activity of midbrain dopamine (DA) neurons requires proper spatial organization of the excitable elements between the soma and dendritic compartments, but the somatodendritic organization is not clear. Here, we show that the dynamic interaction between the soma and multiple proximal dendritic compartments (PDCs) generates the slow pacemaking activity in DA neurons. In multipolar DA neurons, spontaneous action potentials (sAPs) consistently originate from the axon-bearing dendrite. However, when the axon initial segment was disabled, sAPs emerge randomly from various primary PDCs, indicating that multiple PDCs drive pacemaking. Ca measurements and local stimulation/perturbation experiments suggest that the soma serves as a stably-oscillating inertial compartment, while multiple PDCs exhibit stochastic fluctuations and high excitability. Despite the stochastic and excitable nature of PDCs, their activities are balanced by the large centrally-connected inertial soma, resulting in the slow synchronized pacemaking rhythm. Furthermore, our electrophysiological experiments indicate that the soma and PDCs, with distinct characteristics, play different roles in glutamate- induced burst-pause firing patterns. Excitable PDCs mediate excitatory burst responses to glutamate, while the large inertial soma determines inhibitory pause responses to glutamate. Therefore, we could conclude that this somatodendritic organization serves as a common foundation for both pacemaker activity and evoked firing patterns in midbrain DA neurons.
PubMed: 38414399
DOI: 10.4196/kjpp.2024.28.2.165 -
ELife Mar 2024Radial neuronal migration is a key neurodevelopmental event for proper cortical laminar organization. The multipolar-to-bipolar transition, a critical step in...
Radial neuronal migration is a key neurodevelopmental event for proper cortical laminar organization. The multipolar-to-bipolar transition, a critical step in establishing neuronal polarity during radial migration, occurs in the subplate/intermediate zone (SP/IZ), a distinct region of the embryonic cerebral cortex. It has been known that the extracellular matrix (ECM) molecules are enriched in the SP/IZ. However, the molecular constitution and functions of the ECM formed in this region remain poorly understood. Here, we identified neurocan (NCAN) as a major chondroitin sulfate proteoglycan in the mouse SP/IZ. NCAN binds to both radial glial-cell-derived tenascin-C (TNC) and hyaluronan (HA), a large linear polysaccharide, forming a ternary complex of NCAN, TNC, and HA in the SP/IZ. Developing cortical neurons make contact with the ternary complex during migration. The enzymatic or genetic disruption of the ternary complex impairs radial migration by suppressing the multipolar-to-bipolar transition. Furthermore, both TNC and NCAN promoted the morphological maturation of cortical neurons in vitro. The present results provide evidence for the cooperative role of neuron- and radial glial-cell-derived ECM molecules in cortical development.
Topics: Animals; Mice; Neurons; Extracellular Matrix; Cerebral Cortex; Cell Movement; Chondroitin Sulfate Proteoglycans
PubMed: 38512724
DOI: 10.7554/eLife.92342 -
Clinical Neurophysiology : Official... Aug 2023Reconstruct compound median nerve action currents using magnetoneurography to clarify the physiological characteristics of axonal and volume currents and their...
OBJECTIVE
Reconstruct compound median nerve action currents using magnetoneurography to clarify the physiological characteristics of axonal and volume currents and their relationship to potentials.
METHODS
The median nerves of both upper arms of five healthy individuals were investigated. The propagating magnetic field of the action potential was recorded using magnetoneurography, reconstructed into a current, and analyzed. The currents were compared with the potentials recorded from multipolar surface electrodes.
RESULTS
Reconstructed currents could be clearly visualized. Axonal currents flowed forward or backward in the axon, arcing away from the depolarization zone, turning about the subcutaneous volume conductor, and returning to the depolarization zone. The zero-crossing latency of the axonal current was approximately the same as the peak of its volume current and the negative peak of the surface electrode potential. Volume current waveforms were proportional to the derivative of axonal ones.
CONCLUSIONS
Magnetoneurography allows the visualization and quantitative evaluation of action currents. The currents in axons and in volume conductors could be clearly discriminated with good quality. Their properties were consistent with previous neurophysiological findings.
SIGNIFICANCE
Magnetoneurography could be a novel tool for elucidating nerve physiology and pathophysiology.
Topics: Humans; Action Potentials; Median Nerve; Axons; Evoked Potentials; Magnetic Fields; Electric Stimulation
PubMed: 37307628
DOI: 10.1016/j.clinph.2023.05.006 -
IScience Mar 2024The hypothalamic suprachiasmatic nucleus (SCN) is composed of heterogenous populations of neurons that express signaling peptides such as vasoactive intestinal...
The hypothalamic suprachiasmatic nucleus (SCN) is composed of heterogenous populations of neurons that express signaling peptides such as vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP) and regulate circadian rhythms in behavior and physiology. SCN neurons acquire functional and morphological specializations from waves of transcription factors (TFs) that are expressed during neurogenesis. However, the generation of SCN neurons has never been achieved. Here we supplemented a highly efficient neuronal conversion protocol with TFs that are expressed during SCN neurogenesis, namely , , , and . Neurons induced from mouse and human fibroblasts predominantly exhibited neuronal properties such as bipolar or multipolar morphologies, GABAergic neurons with expression of VIP. Our study reveals a critical contribution of these TFs to the development of vasoactive intestinal peptide (Vip) expressing neurons in the SCN, suggesting the regenerative potential of neuronal subtypes contained in the SCN for future SCN regeneration and disease remodeling.
PubMed: 38384840
DOI: 10.1016/j.isci.2024.109051 -
Folia Histochemica Et Cytobiologica 2024Nitric oxide (NO) is present in various cell types in the central nervous system and plays a crucial role in the control of various cellular functions. The diurnal...
INTRODUCTION
Nitric oxide (NO) is present in various cell types in the central nervous system and plays a crucial role in the control of various cellular functions. The diurnal Mongolian gerbil is a member of the rodent family Muridae that exhibits unique physiological, anatomical, and behavioral differences from the nocturnal rat and mouse, which render it a useful model for studying the visual system. The purpose of this study was to confirm the distribution and morphology of neurons that contain nitric oxide synthase (NOS) and their pattern of co-expressing NOS with neuropeptide Y (NPY), somatostatin (SST), and gamma-aminobutyric acid (GABA) in the visual cortex of Mongolian gerbils.
MATERIALS AND METHODS
Mongolian gerbils were used in the study. We confirmed the localization of NOS in the visual cortex of Mongolian gerbils using horseradish peroxidase immunocytochemistry, fluorescent immunocytochemistry, and conventional confocal microscopy.
RESULTS
NOS-immunoreactive (IR) neurons were present in all layers of the visual cortex of the Mongolian gerbil, with the exception of layer I, with the highest density observed in layer V (50.00%). The predominant type of NOS-IR neurons was multipolar round/oval cells (60.96%). Two-color immunofluorescence revealed that 100% NOS-IR neurons were co-labeled with NPY and SST and 34.55% were co-labeled with GABA.
CONCLUSIONS
Our findings of the laminar distribution and morphological characteristics of NOS-IR neurons, as well as the colocalization patterns of NOS-IR neurons with NPY, SST, and GABA, indicated the presence of species-specific differences, suggesting the functional diversity of NO in the visual cortex. This study provides valuable data on the anatomical organization of NOS-IR neurons and, consequently, a better understanding of the functional aspects of NO and species diversity.
Topics: Rats; Mice; Animals; Gerbillinae; Neurons; Nitric Oxide Synthase; Visual Cortex; gamma-Aminobutyric Acid
PubMed: 38563048
DOI: 10.5603/fhc.99227