02-NeuronsGlia-Fall2024.pdf

Neurons & Glia Chapter 2  – Discuss the historical context & histological methods that lead to the neuron doctrine Learning – Learn about the basic cell biology of neurons and their classifications objectives – Understand the role of glial cells in t...

Neurons & Glia Chapter 2  – Discuss the historical context & histological methods that lead to the neuron doctrine Learning – Learn about the basic cell biology of neurons and their classifications objectives – Understand the role of glial cells in the central nervous system (CNS) and peripheral nervous system (PNS)  – Histology (histos, tissue) is the microscopic study of tissue structure. – Two types of histology techniques (stains) paved the way for our modern understanding of neuroscience: – Nissl stain / Cresyl Violet (named after Franz Nissl) – stains blue Histology – Facilitates the study of cytoarchitecture in the CNS Nissl stain of ventral horn – looks at spacial area – Golgi stain (named after Camillo Golgi) – Allow you to look at the structure – Allows differentiation of soma and perikaryon – Neurites: axons and dendrites Golgi stain of subiculum  – Histology (histos, tissue) is the microscopic study of tissue structure. – Two types of histology techniques (stains) paved the way for our modern understanding of neuroscience: – Nissl stain / Cresyl Violet (named after Histology Franz Nissl) – Facilitates the study of cytoarchitecture in the CNS – Golgi stain (named after Camillo Golgi) – Allows differentiation of soma and perikaryon – Neurites: axons and dendrites Basic parts of a neuron  – Various dyes (such as cresyl violet) target negatively-charged molecules – namely, DNA & RNA – Accumulation of DNA & RNA molecules in ribosomes & endoplasmic reticulum of neuronal cell bodies are called “Nissl bodies” Nissl stains – Nissl bodies therefore “drink up” lots of dye Nissl stain of ventral horn – 40x magnification vs. 5x and are easily visualized with this staining technique – Good for figuring out anatomical neuronal cell body distribution / density – Where they are – How they are spaced  – Silver nitrate + potassium dichromate are applied to preserved (“fixed”) tissue – Random cells in the area will pick up the chemicals and get completely filled with micro-crystalized silver chromate (think of wax mold) – Good for figuring out detailed cell morphology (shape/structure) Golgi stains From Dr. Zhou’s 2020 paper: https://elifesciences.org/articles/55569  – Neuron doctrine – fundamental ”doctrine” of neuroscience – Neurons adhere to cell theory: individual neurons are the smallest anatomical building blocks of the nervous system – Neural circuitry: way and which the neurons communicate with each other are the key – Neurons communicate by contact, not continuity not physically linked to each other (in contrast to Golgi’s ideology) – Santiago Ramon y Cajal figured this out after using Golgi staining to study The Neuron neuroanatomy Doctrine Basic parts of a neuron  – Discuss the historical context & histological methods that lead to the neuron doctrine Learning – Learn about the basic cell biology of neurons and their classifications objectives – Understand the role of glial cells in the central nervous system (CNS) and peripheral nervous system (PNS)  – Neurons (nerve cells) are structural units of nervous system – Large, highly specialized cells that conduct impulses – Special characteristics – Extreme longevity (lasts a person’s lifetime) Cells of the – Amitotic, with few exceptions: Can’t make new neurons nervous – High metabolic rate: requires continuous supply of system oxygen and glucose – All have cell body (soma) and one or more processes  – Also called the perikaryon or soma – Biosynthetic center of neuron – Contains spherical nucleus with nucleolus – In most, plasma membrane is part of receptive The neuron region that receives input info from other neurons cell body – Most neuron cell bodies are located in CNS (soma) – Nuclei: clusters of neuron cell bodies in CNS – Ganglia: clusters of neuron cell bodies in PNS  – The soma or cell body contains: – Cytosol: watery fluid inside the Components cell of the – Organelles: membrane-enclosed structures within the soma neuronal – Cytoplasm: contents within a cell membrane (e.g., organelles, soma excluding the nucleus) Internal structure of a typical neuron  – Inside the soma we have the nucleus which is responsible for: – Gene expression – Transcription – RNA processing Components – Neuronal genes are special due to genetic variation and genetic of the engineering neuronal – Neurons differ from other cells because of specific genes. soma – Sequencing of human genome – Genetic basis of many diseases of the nervous system – Role of genetic engineering and gene targeting Internal structure of a typical neuron  – We also have ribosomes in the soma: – Major site of protein Components synthesis of the – Studded on rough endoplasmic reticulum neuronal (ER) – Protein synthesis also soma on free ribosomes; polyribosomes  – Smooth ER and Golgi apparatus are also in the soma – Sites for preparing/sorting proteins for delivery to different cell regions (trafficking) and regulating substances Components of the neuronal soma Components – ~Mitochondria is the powerhouse of the cell of the (soma)~ – Site of cellular respiration (energy generation) neuronal – Krebs cycle / electron transport chain soma – ATP is cell’s energy source  – Central component of electrical functioning in the nervous system – Barrier that encloses the entire neuron The neuronal – ~5 nm thick – Protein concentration in membrane membrane varies. – Structure of discrete membrane regions influences neuronal function. Neuronal membrane channels & their role in electrical activity  – The cytoskeleton – Not static (squirming structures!) – Internal scaffolding of neuronal membrane – Made up of three structures: – Microtubules – Thick hollow-walled pipes made of tubulin “beads” that can polymerize The together to form various shapes – Microtuble-associated proteins cytoskeleton (MAPs) implicated in dementia – Microfilaments – Tiny tubes of actin protein that constantly change shape as needed – Neurofilaments – Like the bones & ligaments of the neuronal skeleton – the strongest & most rigid  – The cytoskeleton – Not static (squirming structures!) – Internal scaffolding of neuronal membrane – Made up of three structures: – Microtubules – Thick hollow-walled pipes made of tubulin “beads” that can polymerize The together to form various shapes – Microtuble-associated proteins cytoskeleton (MAPs) implicated in dementia – Microfilaments – Tiny tubes of actin protein that constantly change shape as needed – Neurofilaments – Like the bones & ligaments of the neuronal skeleton – the strongest & most rigid Also from Dr. Zhou’s 2020 paper: https://elifesciences.org/articles/55569  – Armlike processes that extend from cell body – CNS contains both neuron cell bodies and their processes – PNS contains chiefly neuron processes – Tracts Parts of the – Bundles of neuron processes in CNS neuron – – Nerves – Bundles of neuron processes in PNS neuron – Two types of processes processes – Dendrites – Axon  – Dendrites – Motor neurons can contain 100s of these short, tapering, diffusely branched processes – Contain same organelles as in cell body – Receptive (input) region of neuron Parts of the – Convey incoming messages toward cell body as graded potentials (short distance signals) neuron – – In many brain areas, finer dendrites are highly specialized to collect information dendrites – Contain dendritic spines, appendages with bulbous or spiky ends Parts of the neuron – dendrites Structure of a motor neuron digitally reconstructed at 1000x magnification  – The axon: structure – Each neuron has one axon that starts at cone-shaped area called axon hillock – In some neurons, axons are short or absent; in others, axon comprises almost entire length of cell – Some axons can be over 1 meter long – Long axons are called nerve fibers Parts of the – Axons have occasional branches called axon collaterals neuron – the – Axons branch profusely at their end (terminus) axon – Can number as many as 10,000 terminal branches – Distal endings are called axon terminals or terminal boutons  – The axon: functional characteristics – Axon is the conducting region of neuron – Generates nerve impulses and transmits them along axolemma (neuron cell membrane) to axon terminal – Terminal: region that secretes neurotransmitters, which are released into extracellular space – Can excite or inhibit neurons it contacts Parts of the – Carries on many conversations with different neurons neuron – the at same time – Axons rely on cell bodies to renew proteins and axon membranes – Quickly decay if cut or damaged  – The axon: functional characteristics (cont.) – Axons have efficient internal transport mechanisms – Molecules and organelles are moved along axons by motor proteins and cytoskeletal elements – Movement occurs in both directions Parts of the – Anterograde: away from cell body – Examples: mitochondria, cytoskeletal elements, membrane components, enzymes neuron – the – Retrograde: toward cell body axon – Examples: organelles to be degraded, signal molecules, viruses, and bacterial toxins  – The axon: functional characteristics (cont.) – Axons have efficient internal transport mechanisms – Molecules and organelles are moved along axons by motor proteins and cytoskeletal elements – Movement occurs in both directions Parts of the – Anterograde: away from cell body – Examples: mitochondria, cytoskeletal elements, membrane components, enzymes neuron – the – Retrograde: toward cell body axon – Examples: organelles to be degraded, signal molecules, viruses, and bacterial toxins  – Certain viruses and bacterial toxins damage neural tissues by using retrograde axonal transport- can determine which dendrites are communicating with eachother Axoplasmic – Example: polio, rabies, and herpes simplex viruses, and tetanus toxin transport – Research is under way to investigate using retrograde transport to treat genetic diseases – Viruses containing “corrected” genes or microRNA to suppress defective genes can enter cell through retrograde transport Rabies virus labeled neurons  – Synaptic transmission is the fundamental way in which neurons communicate with each other – Usually occurs between an axon à subsequent dendrite of next neuron, but other types of synapses exist which we’ll learn about later The synapse – Electrical-to-chemical-to-electrical transformation – Synaptic transmission dysfunction leads to mental disorders.  – Structural classification – Three types grouped by number of processes 1. Multipolar: three or more processes (1 axon, others dendrites) – Most common and major neuron type in CNS 2. Bipolar: two processes (one axon, 1one dendrite) – Rare (ex: retina and olfactory mucosa) eyeball, nose 3. Unipolar: one T-like process (two axons) – Also called pseudounipolar Classifications – Peripheral (distal) process: associated with sensory receptor of neurons – Proximal (central) process: enters CNS Classifications of neurons Classifications of neurons  – Functional classification of neurons – Three types of neurons grouped by direction in which nerve impulse travels relative to CNS 1. Sensory – Transmit impulses from sensory receptors toward CNS – Almost all are unipolar Functional 2. – Cell bodies are located in ganglia in PNS Motor classifications – Carry impulses from CNS to effectors – Multipolar of neurons – Most cell bodies are located in CNS (except some autonomic neurons) 3. Interneurons – Also called association neurons – Lie between motor and sensory neurons – Shuttle signals through CNS pathways – Most are entirely within CNS – 99% of body’s neurons are interneurons Functional classifications of neurons  – Classification of neurons based on gene expression is one of the “newest” ways we can categorize them – Creation of transgenic mice – Transgenic = genes inserted into the organism’s genome that weren’t originally there, often used to genetically “tag” cells – Green fluorescent protein Genetic – Classification based on classifications neurotransmitter type – “Cholinergic” of neurons – ”Serotonergic” – ”Dopaminergic” Also from Dr. Zhou’s 2020 paper: https://elifesciences.org/articles/55569  – Discuss the historical context & histological methods that lead to the neuron doctrine Learning – Learn about the basic cell biology of neurons and their classifications objectives – Understand the role of glial cells in the central nervous system (CNS) and peripheral nervous system (PNS)  – Four main neuroglia support CNS neurons – Astrocytes – Microglial cells – Ependymal cells Glia are the – Oligodendrocytes “support” cells of the nervous system  – Astrocytes – Most abundant, versatile, and highly branched of glial cells – Cling to neurons, synaptic endings, and capillaries – Functions include: – Support and brace neurons – Play role in exchanges between capillaries and CNS Glia neurons – Guide migration of young neurons – Control chemical environment around neurons – Respond to nerve impulses and neurotransmitters – Influence neuronal functioning – Participate in information processing in brain  – Microglial cells – Small, ovoid cells with thorny processes that touch and monitor neurons CNS Glia – Migrate toward injured neurons – Can transform to phagocytize microorganisms and neuronal debris  – Ependymal cells – Range in shape from squamous to columnar – May be ciliated – Cilia beat to circulate CSF – Line the central cavities of the brain and spinal column – Form permeable barrier between cerebrospinal fluid (CSF) in cavities and tissue fluid bathing CNS cells CNS Glia  – Oligodendrocytes – Branched cells – Processes wrap CNS nerve fibers, forming insulating myelin sheaths in thicker nerve fibers CNS Glia  – Composed of myelin, a whitish, protein- lipid substance – Function of myelin – Make sure no particles are leaking out – Protect and electrically insulate axon – Increase speed of nerve impulse Myelin sheath transmission – Myelinated fibers: segmented sheath surrounds most long or large-diameter axons – Nonmyelinated fibers: do not contain sheath – Conduct impulses more slowly  – Myelin sheaths in the CNS – Formed by processes of oligodendrocytes, not whole cells – Each cell can wrap up to 60 axons at once – Myelin sheath gap is present – No outer collar of perinuclear cytoplasm – Thinnest fibers are unmyelinated, but covered by long extensions of adjacent neuroglia – White matter: regions of brain and spinal cord with dense collections of myelinated fibers – Usually fiber tracts Myelin sheath – Gray matter: mostly neuron cell bodies and nonmyelinated fibers  – Two major neuroglia seen in PNS – Satellite cells – Surround neuron cell bodies in PNS – Function similar to astrocytes of CNS – Schwann cells (neurolemmocytes) – Surround all peripheral nerve fibers and form myelin sheaths in thicker nerve fibers – Similar function as oligodendrocytes – Vital to regeneration of damaged peripheral nerve fibers PNS Glia  – Myelination in the PNS – Formed by Schwann cells – Wraps around axon in jelly roll fashion – One cell forms one segment of myelin sheath Myelin sheath – Outer collar of perinuclear cytoplasm (formerly called neurilemma): peripheral in the PNS bulge containing nucleus and most of cytoplasm – Plasma membranes have less protein – No channels or carriers, so good electrical insulators – Interlocking proteins bind adjacent myelin membranes Myelin sheath in the PNS  – Myelination in the PNS (cont.) – Myelin sheath gaps – Gaps between adjacent Schwann cells – Sites where axon collaterals can emerge – Formerly called nodes of Ranvier Myelin sheath – Nonmyelinated fibers – Thin fibers not wrapped in myelin; surrounded in the PNS by Schwann cells but no coiling; one cell may surround 15 different fibers Quiz hint! – Types of glia & their general functions Questions?