Catecholamine neurons of the locus coeruleus (LC) in the dorsal pontine tegmentum innervate the entire neuroaxis, with signaling actions implicated in the regulation of attention, arousal, sleep–wake ...cycle, learning, memory, anxiety, pain, mood, and brain metabolism. The co‐release of norepinephrine (NE) and dopamine (DA) from LC terminals in the hippocampus plays a role in all stages of hippocampal‐memory processing. This catecholaminergic regulation modulates the encoding, consolidation, retrieval, and reversal of hippocampus‐based memory. LC neurons in awake animals have two distinct firing modes: tonic firing (explorative) and phasic firing (exploitative). These two firing modes exert different modulatory effects on post‐synaptic dendritic spines. In the hippocampus, the firing modes regulate long‐term potentiation (LTP) and long‐term depression, which differentially regulate the mRNA expression and transcription of plasticity‐related proteins (PRPs). These proteins aid in structural alterations of dendritic spines, that is, structural long‐term potentiation (sLTP), via expansion and structural long‐term depression (sLTD) via contraction of post‐synaptic dendritic spines. Given the LC's role in all phases of memory processing, the degeneration of 50% of the LC neuron population occurring in Alzheimer's disease (AD) is a clinically relevant aspect of disease pathology. The loss of catecholaminergic regulation contributes to dysfunction in memory processes along with impaired functions associated with attention and task completion. The multifaceted role of the LC in memory and general task performance and the close correlation of LC degeneration with neurodegenerative disease progression together implicate it as a target for new clinical assessment tools.
In the Alzheimer's Brian, degenerated LC input reduces hippocampal plasticity and impairs memory, whereas it promotes plasticity and memory in a health brain. Graphical artwork was done by Annabel Driussi.
The fluorescence viewing of mitochondria is commonly performed by MitoTracker, a lipophilic cationic dye that is taken up by the mitochondria. In this forum, we highlight several issues that may ...occur with MitoTracker, including staining of other organelles. Our aim is to offer alternative dyes and discuss their advantages and disadvantages. We also offer options for software with alternatives to MitoTracker to expedite future experimental design.
This review provides an overview of the current methods for quantifying mitochondrial ultrastructure, including cristae morphology, mitochondrial contact sites, and recycling machinery and a guide to ...utilizing electron microscopy to effectively measure these organelles. Quantitative analysis of mitochondrial ultrastructure is essential for understanding mitochondrial biology and developing therapeutic strategies for mitochondrial-related diseases. Techniques such as transmission electron microscopy (TEM) and serial block face-scanning electron microscopy, as well as how they can be combined with other techniques including confocal microscopy, super-resolution microscopy, and correlative light and electron microscopy are discussed. Beyond their limitations and challenges, we also offer specific magnifications that may be best suited for TEM analysis of mitochondrial, endoplasmic reticulum, and recycling machinery. Finally, perspectives on future quantification methods are offered.
•Suggestions for transmission electron microscopy measurement of mitochondria, their contact sites, and recycling machinery.•Measurement techniques for mitochondria, their contact sites, recycling machinery, endoplasmic reticulum, and Golgi Apparatus.•Critique of the current literature regarding TEM quantification and considerations for future 3D analysis.•TEM from our laboratory across a range of tissues demonstrating the functional impact of these literature-backed suggestions.
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 (Ca2+ permeable) or the pore-dead GluA2 subunit of AMPARs triggered proliferation of OPCs and reduced their differentiation into oligodendrocytes. Expression of the cytoplasmic C-terminal (GluA2(813-862)) of the GluA2 subunit (C-tail), a modification designed to affect the interaction between GluA2 and AMPAR-binding proteins and to perturb trafficking of GluA2-containing AMPARs, decreased the differentiation of OPCs without affecting their proliferation. These findings suggest that ionotropic and non-ionotropic properties of AMPARs in OPCs, as well as specific aspects of AMPAR-mediated signaling at axon-OPC synapses in the mouse corpus callosum, are important for balancing the response of OPCs to proliferation and differentiation cues.
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•AMPA receptors (AMPARs) with modified properties are expressed in OPCs in vivo•Channel-pore mutations of AMPARs affect functional properties of axon-OPC synapses•Expression of Ca2+-permeable AMPARs alters proliferation and differentiation of OPCs•Introducing the C-tail of the GluA2 subunit of AMPARs reduces differentiation of OPCs
In the brain, oligodendrocyte precursor cells (OPCs) receive glutamatergic AMPA-receptor-mediated synaptic input from neurons. Chen et al. show that modifying AMPA-receptor properties at axon-OPC synapses alters proliferation and differentiation of OPCs. This expands the traditional view of synaptic transmission by suggesting neurons also use synapses to modulate behavior of glia.
ABSTRACT
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. Intriguingly, neurons establish glutamatergic synapses also with oligodendrocyte precursor cells (NG2+‐glia). Moreover, neuronal activity and glutamate receptors play an important role in the development and functionality of oligodendrocytes and their precursors in vivo. Yet, molecular characteristics and functional significance of neuron–glia synapses remain poorly understood, and it is unclear how glutamate receptors mediate the effects of neuronal activity on the oligodendrocyte lineage cells. In this review, we discuss what is known with regard to synaptic and non‐synaptic glutamatergic signaling between neurons and oligodendrocyte lineage cells, what can be suggested based on the current state of knowledge, and what is fully unknown and requires new research.
Main points
Oligodendroglia express glutamate receptors which may be activated by synaptically released glutamate or volume transmission.
Glutamatergic neuron‐oligodendroglia signaling is important for development and functionality of oligodendrocytes and their precursors.
Mitochondrial dysfunction has long been implicated in the development of insulin resistance, which is a hallmark of type 2 diabetes. However, recent studies reveal ethnicity-related differences in ...mitochondrial processes, underscoring the need for nuance in studying mitochondrial dysfunction and insulin sensitivity. Furthermore, the higher prevalence of type 2 diabetes among African Americans and individuals of African descent has brought attention to the role of ethnicity in disease susceptibility. In this review, which covers existing literature, genetic studies, and clinical data, we aim to elucidate the complex relationship between mitochondrial alterations and insulin stimulation by considering how mitochondrial dynamics, contact sites, pathways, and metabolomics may be differentially regulated across ethnicities, through mechanisms such as single nucleotide polymorphisms (SNPs). In addition to achieving a better understanding of insulin stimulation, future studies identifying novel regulators of mitochondrial structure and function could provide valuable insights into ethnicity-dependent insulin signaling and personalized care.
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. We established a novel preparation of living peripheral nerve slices with preserved cellular architecture and used a patch-clamp technique to study AMPA-receptor (AMPAR)-mediated currents in SCs for the first time. We found that the majority of SCs in the nerves dissected from embryonic and neonatal mice of both sexes respond to the application of glutamate with inward current mediated by Ca
-permeable AMPARs. Using stationary fluctuation analysis (SFA), we demonstrate that single-channel conductance of AMPARs in SCs is 8-11 pS, which is comparable to that in neurons. We further show that, when SCs become myelinating, they downregulate functional AMPARs. This study is the first to demonstrate AMPAR-mediated conductance in SCs of vertebrates, to investigate elementary properties of AMPARs in these cells, and to provide detailed electrophysiological and morphological characterization of SCs at different stages of development.
We provide several important conceptual and technical advances in research on the PNS. We pioneer the first description of AMPA receptor (AMPAR)-mediated currents in the PNS glia of vertebrates and provide new insights into the properties of AMPAR channels in peripheral glia; for example, their Ca
permeability and single-channel conductance. We describe for the first time the electrophysiological and morphological properties of Schwann cells (SCs) at different stages of development and show that functional AMPARs are expressed only in developing, not mature, SCs. Finally, we introduce a preparation of peripheral nerve slices for patch-clamp recordings. This preparation opens new possibilities for studying the physiology of SCs in animal models and in surgical human samples.
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. In this study, we pharmacologically blocked GLUT4 to investigate the effects of exogenous KB D-ꞵ-hydroxybutyrate (D-ꞵHb) on mouse brain metabolism during acute insulin resistance (AIR). We found that both AIR and D-ꞵHb had distinct impacts across neuronal compartments: AIR decreased synaptic activity and long-term potentiation (LTP) and impaired axonal conduction, synchronization, and action potential properties, while D-ꞵHb rescued neuronal functions associated with axonal conduction, synchronization, and LTP.
The aim of the study was to investigate the impact of air pollution and meteorological conditions
on visibility in Zakopane, the most popular tourist destination in southern Poland. To achieve
this ...objective, correlation analysis, multiple linear regression analysis and random forests were
used. In addition, an analysis was performed of the occurrence of episodes of elevated pollutant
concentrations and basic statistical characteristics of visibility, meteorological conditions and air
pollution. Meteorological parameters (air temperature, relative humidity, total precipitation, wind
speed, atmospheric pressure and visibility) and concentrations of air pollutants; particulate matter
(PM₁₀) and gaseous pollutants (SO₂, NO₂) were recorded from 2010 to 2019. The data came from
a monitoring station located in Zakopane-MpZakopaSien. It was found that high concentrations
of air pollutants SO₂ and PM₁₀, along with relative humidity (RH), were the most important
parameters affecting visibility limitation in Zakopane. Concentrations and indirectly also visibility
were largely influenced by increased automobile traffic due to tourist activity, as well as emissions
from apartment/building heating (combustion of various fuels). Understanding the relationship
between air pollutant concentrations, meteorological conditions and visibility is a prerequisite and the basis for the scientific formulation of air pollution prevention and control policies in places
where monitoring is particularly important.
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