Hidden in the white matter: Current views on interstitial white matter neurons.

The mammalian brain comprises two structurally and functionally distinct compartments: the gray matter (GM) and the white matter (WM). In humans, the WM constitutes approximately half of the brain volume, yet it remains significantly less investigated than the GM. The major cellular elements of the WM are neuronal axons and glial cells.

D-ꞵ-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance.

The brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KBs) when less glucose is available. Neuronal KB uptake, which does not rely on glucose transporter 4 (GLUT4) or insulin, has shown promising clinical applicability in alleviating the neurological and cognitive effects of disorders with hypometabolic components. However, the specific mechanisms by which such interventions affect neuronal functions are poorly understood.

-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance.

The brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KBs) when less glucose is available. Neuronal KB uptake, which does not rely on glucose transporter 4 (GLUT4) or insulin, has shown promising clinical applicability in alleviating the neurological and cognitive effects of disorders with hypometabolic components. However, the specific mechanisms by which such interventions affect neuronal functions are poorly understood.

Understanding the Role of the Glial Scar through the Depletion of Glial Cells after Spinal Cord Injury.

Spinal cord injury (SCI) is a condition that affects between 8.8 and 246 people in a million and, unlike many other neurological disorders, it affects mostly young people, causing deficits in sensory, motor, and autonomic functions. Promoting the regrowth of axons is one of the most important goals for the neurological recovery of patients after SCI, but it is also one of the most challenging goals.

Recent Insights into the Functional Role of AMPA Receptors in the Oligodendrocyte Lineage Cells In Vivo.

This review discusses the experimental findings of several recent studies which investigated the functional role of AMPA receptors (AMPARs) in oligodendrocyte lineage cells in vivo, in mice and in zebrafish. These studies provided valuable information showing that oligodendroglial AMPARs may be involved in the modulation of proliferation, differentiation, and migration of oligodendroglial progenitors, as well as survival of myelinating oligodendrocytes during physiological conditions in vivo. They also suggested that targeting the subunit composition of AMPARs may be an important strategy for treating diseases.

Technical approaches and challenges to study AMPA receptors in oligodendrocyte lineage cells: Past, present, and future.

Receptors for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPARs) are ligand-gated ionotropic receptors for glutamate that is a major excitatory neurotransmitter in the central nervous system. AMPARs are located at postsynaptic sites of neuronal synapses where they mediate fast synaptic signaling and synaptic plasticity. Remarkably, AMPARs are also expressed by glial cells.

Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?

Despite significant advances in our understanding of the pathophysiology of multiple sclerosis (MS), knowledge about contribution of individual ion channels to axonal impairment and remyelination failure in progressive MS remains incomplete. Ion channel families play a fundamental role in maintaining white matter (WM) integrity and in regulating WM activities in axons, interstitial neurons, glia, and vascular cells. Recently, transcriptomic studies have considerably increased insight into the gene expression changes that occur in diverse WM lesions and the gene expression fingerprint of specific WM cells associated with secondary progressive MS.

[The experiment of searching a biological origin traces with an expert light source].

The aim of the work is assessment of the efficiency of detection the biological traces by various sources of expert light. Hidden traces of blood, saliva, semen and urine were detecting on various types of carrier objects. Was described the biological appearance depended on both the nature of the material and the properties of the carrier object: color, the presence of luminescent substances in the composition, the nature of the surface (smooth, fleecy), thickness, ability to adsorb and conduct liquid.

Glutamate receptors and glutamatergic signalling in the peripheral nerves.

In the peripheral nervous system, the vast majority of axons are accommodated within the fibre bundles that constitute the peripheral nerves. Axons within the nerves are in close contact with myelinating glia, the Schwann cells that are ideally placed to respond to, and possibly shape, axonal activity. The mechanisms of intercellular communication in the peripheral nerves may involve direct contact between the cells, as well as signalling via diffusible substances.

Glutamatergic signaling between neurons and oligodendrocyte lineage cells: Is it synaptic or non-synaptic?

Fast chemical synaptic transmission is a major form of neuronal communication in the nervous system of mammals. Another important, but very different, form of intercellular communication is volume transmission, which is a slower non-synaptic signaling. The amino acid glutamate is the most abundant excitatory neurotransmitter in the nervous system, which mediates both synaptic and non-synaptic signaling via ionotropic and metabotropic glutamate receptors.

In Vivo Regulation of Oligodendrocyte Precursor Cell Proliferation and Differentiation by the AMPA-Receptor Subunit GluA2.

The functional role of AMPA receptor (AMPAR)-mediated synaptic signaling between neurons and oligodendrocyte precursor cells (OPCs) remains enigmatic. We modified the properties of AMPARs at axon-OPC synapses in the mouse corpus callosum in vivo during the peak of myelination by targeting the GluA2 subunit. Expression of the unedited (Ca permeable) or the pore-dead GluA2 subunit of AMPARs triggered proliferation of OPCs and reduced their differentiation into oligodendrocytes.

Glutamate Activates AMPA Receptor Conductance in the Developing Schwann Cells of the Mammalian Peripheral Nerves.

Schwann cells (SCs) are myelinating cells of the PNS. Although SCs are known to express different channels and receptors on their surface, little is known about the activation and function of these proteins. Ionotropic glutamate receptors are thought to play an essential role during development of SC lineage and during peripheral nerve injury, so we sought to study their functional properties.

Different patterns of neuronal activity trigger distinct responses of oligodendrocyte precursor cells in the corpus callosum.

In the developing and adult brain, oligodendrocyte precursor cells (OPCs) are influenced by neuronal activity: they are involved in synaptic signaling with neurons, and their proliferation and differentiation into myelinating glia can be altered by transient changes in neuronal firing. An important question that has been unanswered is whether OPCs can discriminate different patterns of neuronal activity and respond to them in a distinct way. Here, we demonstrate in brain slices that the pattern of neuronal activity determines the functional changes triggered at synapses between axons and OPCs.

N- and L-Type Voltage-Gated Calcium Channels Mediate Fast Calcium Transients in Axonal Shafts of Mouse Peripheral Nerve.

In the peripheral nervous system (PNS) a vast number of axons are accommodated within fiber bundles that constitute peripheral nerves. A major function of peripheral axons is to propagate action potentials along their length, and hence they are equipped with Na(+) and K(+) channels, which ensure successful generation, conduction and termination of each action potential. However little is known about Ca(2+) ion channels expressed along peripheral axons and their possible functional significance.

Effects of the jimpy mutation on mouse retinal structure and function.

The Jimpy mutant mouse has a point mutation in the proteolipid protein gene (plp1). The resulting misfolding of the protein leads to oligodendrocyte death, myelin destruction, and failure to produce adequately myelinated axons in the central nervous system (CNS). It is not known how the absence of normal myelination during development influences neural function.

Hyperpolarization-activated cation current Ih of dentate gyrus granule cells is upregulated in human and rat temporal lobe epilepsy.

The hyperpolarization-activated cation current I(h) is an important regulator of neuronal excitability and may contribute to the properties of the dentate gyrus granule (DGG) cells, which constitute the input site of the canonical hippocampal circuit. Here, we investigated changes in I(h) in DGG cells in human temporal lobe epilepsy (TLE) and the rat pilocarpine model of TLE using the patch-clamp technique. Messenger-RNA (mRNA) expression of I(h)-conducting HCN1, 2 and 4 isoforms was determined using semi-quantitative in-situ hybridization.

Depression of release by mGluR8 alters Ca2+ dependence of release machinery.

The ubiquitous presynaptic metabotropic glutamate receptors (mGluRs) are generally believed to primarily inhibit synaptic transmission through blockade of Ca(2+) entry. Here, we analyzed how mGluR8 achieves a nearly complete inhibition of glutamate release at hippocampal synapses. Surprisingly, presynaptic Ca(2+) imaging and miniature excitatory postsynaptic current recordings showed that mGluR8 acts without affecting Ca(2+) entry, diffusion, and buffering.

Fate of neuron-glia synapses during proliferation and differentiation of NG2 cells.

Progenitor cells expressing proteoglycan NG2 (also known as oligodendrocyte precursor cells or polydendrocytes) are widespread in the grey and white matter of the CNS; they comprise 8-9% of the total cell population in adult white matter, and 2-3% of total cells in adult grey matter. NG2 cells have a complex stellate morphology, with highly branched processes that may extend more than 100 μm around the cell body. NG2 cells express a complex set of voltage-gated channels, AMPA/kainate and/or γ-aminobutyric acid (GABA)(A) receptors, and receive glutamatergic and/or GABAergic synaptic input from neurons.

The fate of synaptic input to NG2 glial cells: neurons specifically downregulate transmitter release onto differentiating oligodendroglial cells.

NG2-expressing oligodendrocyte precursor cells (OPCs) are ubiquitous and generate oligodendrocytes throughout the young and adult brain. Previous work has shown that virtually every NG2 cell receives synaptic input from many axons, but the meaning of this signaling is not understood. In particular, it is unclear whether neurons specifically synapse onto OPCs or whether OPCs merely trace adjacent neurotransmitter release sites and are not recognized by the presynaptic neuron.

Kainate receptors and signal integration by NG2 glial cells.

It is well established that NG2 cells throughout the young and adult brain consistently detect the release of single vesicles filled with glutamate from nearby axons. The released neurotransmitter glutamate electrically excites NG2 cells via non-NMDA (N-methyl-D-aspartic acid) glutamate receptors but the individual contribution of AMPA and kainate receptors to neuron-NG2 cell signalling, is not well understood. Here we pharmacologically block AMPA-type glutamate receptors and investigate whether hippocampal NG2 cells also express the kainate subtype of glutamate receptors and what may be their contribution to synaptic connectivity.

Synapses on NG2-expressing progenitors in the brain: multiple functions?

Progenitor cells expressing the proteoglycan NG2 represent approximately 5% of the total cells in the adult brain, and are found both in grey and white matter regions where they give rise to oligodendrocytes. The finding that these cells receive synaptic contacts from excitatory and inhibitory neurons has not only raised major interest in the possible roles of these synapses, but also stimulated further research on the developmental and cellular functions of NG2-expressing (NG2(+)) progenitors themselves in the context of neural circuit physiology. Here we review recent findings on the functional properties of the synapses on NG2(+) cells in grey and white matter regions of the brain.

Glial cells are born with synapses.

In postnatal rodent brain, certain NG2-expressing oligodendroglial precursor cells (OPCs) are contacted by synaptic terminals from local neurons. However, it has remained elusive whether and when NG2(+) cells are integrated into neuronal circuits. Here we use patch-clamp recordings from mitotic cells in murine brain slices to show that, unlike any other cell in the central nervous system (CNS), cortical NG2(+) cells divide and relocate while being linked to synaptic junctions.

TBOA-sensitive uptake limits glutamate penetration into brain slices to a few micrometers.

Removal of neurotransmitter from the extracellular space is crucial for normal functioning of the central nervous system. In this study, we have used high-affinity metabotropic glutamate receptors (mGluRs) expressed by hippocampal CA1 pyramidal cells to test how far bath-applied glutamate penetrates into slice tissue before being removed by uptake mechanisms. Activation of group I mGluRs by 100 microM DHPG produced an inward current of -48+/-10pA (I(mGluR)), which was blocked by application of group I mGluR antagonists.

Vesicular glutamate release from axons in white matter.

Vesicular release of neurotransmitter is the universal output signal of neurons in the brain. It is generally believed that fast transmitter release is restricted to nerve terminals that contact postsynaptic cells in the gray matter. Here we show in the rat brain that the neurotransmitter glutamate is also released at discrete sites along axons in white matter in the absence of neurons and nerve terminals.