2. Neuroscience: Neuron Structure and Function

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Questions and Answers

What role do microfilaments primarily play in neurons?

Maintaining membrane integrity and cell morphology (correct)

Myelination of axons

Facilitation of neurotransmitter release

Transporting organelles along the axon

What is the difference between fast and slow axonal transport?

Fast transport is slower than slow transport.

Fast transport is mediated exclusively by microfilaments.

Fast transport occurs at approximately 400 mm/day. (correct)

Slow transport involves a known recognition mechanism.

Which factor stimulates myelination in neurons?

Decreased ATP availability in axons

Increased oxidative stress in oligodendrocytes

Inhibition of action potential generation

Release of Leukaemia Inducing Factor (LIF) (correct)

Which of the following is a symptom of multiple sclerosis?

Cognitive deficits (rarely) Signup and view all the answers

What makes oligodendrocytes particularly vulnerable in the central nervous system?

High metabolic demand and oxidative stress Signup and view all the answers

Which type of neuronal firing pattern consistently produces action potentials?

Tonic / regular firing Signup and view all the answers

What is the primary function of the soma in a neuron?

Protein synthesis and degradation Signup and view all the answers

Which component of the neuronal cytoskeleton is primarily involved in cellular transport?

Microtubules Signup and view all the answers

Neurofilaments are most commonly found in which part of a neuron?

Axons Signup and view all the answers

What neurological disorders are associated with the dysfunction of microtubules?

Alzheimer’s and Charcot-Marie-Tooth disease Signup and view all the answers

What is the primary function of GABAergic interneurones?

Prevent overactivity in neuronal circuits Signup and view all the answers

Which neuronal type typically has long axons that project to other parts of the CNS?

Projection neurones Signup and view all the answers

What is the diameter range of proximal dendrites?

1-5 μm Signup and view all the answers

How are neurotransmitters classified in neurons?

By their chemical structure and function Signup and view all the answers

What type of neurones are typically found in the central nervous system with a cell soma and multiple processes?

Multipolar neurones Signup and view all the answers

Which neurotransmitter is primarily associated with inhibitory neurotransmission?

GABA Signup and view all the answers

What distinguishes relay neurones from projection neurones?

Relay neurones have shorter axons Signup and view all the answers

Which of the following is a non-classical neurotransmitter?

ATP Signup and view all the answers

What is one of the key roles of ependymal cells in the central nervous system?

Produce and regulate cerebrospinal fluid Signup and view all the answers

Which type of glial cell is specifically associated with the myelination of peripheral nerves?

Schwann cells Signup and view all the answers

What role do radial cells play in neural development?

Serve as progenitor cells for neurons and glia Signup and view all the answers

What major function do astrocytes provide in the central nervous system?

Metabolic and structural support Signup and view all the answers

Which glial cells are considered the main immune cells of the central nervous system?

Microglia Signup and view all the answers

What are the primary types of cells in the brain?

Neurones and Glia Signup and view all the answers

What key components make up a neurone?

Dendrites, soma, axon Signup and view all the answers

Which of the following classification methods for neurones is NOT mentioned?

Location Signup and view all the answers

Which staining technique identifies the entirety of a cell?

Golgi stain Signup and view all the answers

What type of neurone relays signals between other neurones?

Interneurones Signup and view all the answers

What is the approximate somatic diameter range of a neurone?

5-50μm Signup and view all the answers

Which of the following pairs of neurones is correctly matched with their function?

Sensory neurones - Afferents to the CNS Signup and view all the answers

Which theory of neuronal organization was proposed by Ramon y Cajal?

Neurone doctrine Signup and view all the answers

Study Notes

Cellular Organisation of the CNS: Neurones & Glia

The brain primarily comprises two cell types: neurones and glia.
Neurones carry signals; glia provide support.
Neurones exhibit diverse morphologies, functions, neurotransmitter types, and electrical activity.
Neuronal classification is complex. Factors to consider include function, morphology, electrical activity, neurotransmitters, and gene expression.

Neurones

Neuronal size: somatic diameter ranges from 5 to 50 µm.
Dendrites: typically 1-10, originating from the soma, ranging in diameter from 1-5 µm (proximal) and 0.2-1 µm (distal); extending ~10-500μm.
Axons: generally thicker and longer than dendrites, typically 1-10 µm in diameter (up to 20 µm); lengths vary significantly (micrometers to millimeters to meters).

Neuronal Classification

Sensory neurones: afferents to the CNS.
Motor neurones: efferents from the CNS.
Interneurones: relay signals between neurones.
- This classification primarily applies to the peripheral nervous system, not the CNS.
Neuronal classification is multifaceted, considering function, morphology, electrical properties, neurotransmitters, and gene expression.

Neurone Doctrine

Historical debate between the reticular and neurone theories of brain structure. Reticular theory proposed continuous network; neurone theory favoured discrete neurones.
Camillo Golgi championed the reticular theory.
Santiago Ramón y Cajal championed the neurone theory, highlighting synaptic junctions.
The neurone doctrine, supporting the concept of discrete neurons communicating via synapses, became firmly established in the 1950s with the discovery of synapses in the brain.

Advances in Histology & Microscopy

Nissl stain (1885): highlighting nucleic acid-rich areas, predominantly endoplasmic reticulum (ER), for cellular identification.
Golgi stain (1873): silver staining that visualizes the entire neuronal structure.

Fluorescence Microscopy

Conventional fluorescence microscopy (late 1970s): utilized for visualizing a wide variety of aspects in biological tissues and cells to improve resolution.
Multiphoton microscopy (1990s): advanced fluorescence techniques revealing enhanced resolution and depth penetration.

Electron Microscopy

High-resolution visualization of cellular structures (e.g., neurons and glia) down to the nanometer region.

Neuronal Structures

Multipolar neurones: the most common type in the CNS; possess numerous dendrites and a single axon.
Bipolar neurones: have two processes, 1 dendrite and 1 axon.
Pseudo-unipolar neurones: single axon that divides into two branches, one extending to the periphery and the other to the CNS.
Unipolar neurones: single process that splits into two branches.

Projection & Local Neurones

Projection neurones: transmit signals across long distances within the CNS; exhibit long axons.
Local/relay neurones: transmit signals within a confined brain region; characterized by short axons.
Projection and relay cells often use neurotransmitters like glutamate, GABA, serotonin, and dopamine.
Interneurones are a type of relay neurone predominantly GABAergic; occasionally are cholinergic or dopaminergic.

GABAergic Interneurones

Inhibitory neurones contributing to the majority of interneurones in the CNS.
Crucial for preventing excessive neuronal activity (e.g., epilepsy).
Regulate signal precision (e.g., visual acuity) and coordinate activity across multiple neurones (e.g., oscillations).

Neuronal Circuit Example

Simple illustration of a projection neurone, a relay neurone (both sending signals in the same direction), and an inhibitory interneurone (sending signals in the opposite direction).

Classification by Neurotransmitter

Major neurotransmitters include glutamate, GABA, acetylcholine, dopamine, serotonin, glycine, noradrenaline, and histamine (collectively, "classical" primary neurotransmitters). Other are comparatively less prevalent.

Classification by Electrical Properties

Firing patterns: categorization by neuronal firing frequency or regularity; include tonic (regular), phasic (burst), and fast spiking.

Neuronal Compartments

Neurones are highly compartmentalized, having different functions in specific regions (e.g., soma for protein synthesis, dendrites for signal reception, axons for signal transmission).

Soma ("Perikaryon")

The cell body containing standard organelles such as the nucleus, Golgi apparatus, and lysosomes.
Unique protein synthesis and degradation site in neurones.

Neuronal Cytoskeleton

Similar to other eukaryotic cells; composed of microtubules, neurofilaments, and microfilaments.
Essential for cell structure, growth, and transport.

Microtubules

Contribute to neuronal transport by facilitating kinesin- and dynein-mediated movement of vesicles and other components.

Neurofilaments

Significant role in structural maintenance and growth of axonal structure.

Microfilaments

Formed from actin; present in dendrites, axons, and growth cones.
Essential for the maintenance of cell shape, membrane integrity, organization of membrane proteins and interaction with the extracellular environment.

Neuronal Cytoskeleton & Transport

Illustrates cellular components of neurones.

Axonal Transport

Transportation of molecules to different parts within the axon and synapse.
Fast axonal transport: high speed, primarily used for organelles and vesicles to move along microtubules, using kinesin and dynein motors.
Slow axonal transport: slower speeds, mainly used for components (e.g., proteins) that move continuously.

More Histology

Stains are carried along axonal transport, for example horseradish peroxidase.
Reverse transport of stains (retrograde transport) enables mapping of neuronal circuits.

Cytoskeleton & Transport in Nervous Pathologies

Key cytoskeletal proteins involved in neurodegenerative diseases (e.g., tau protein in Alzheimer's disease, neurofilaments in Charcot-Marie-Tooth disease).

Dendrites

Start as extensions of the perikaryon, tapering and branching as they extend.
Primary receptive area of the neuron.
Dendritic spines are numerous, small protrusions on dendrites, important areas of synapse formation.

Dendritic Spines

Membranous extensions of dendrites forming postsynaptic parts of synapses.
Essential for proper synaptic function.
Structure and contents crucial for synaptic function.
Compartmentalisation (the spine neck) restricts movement between the spine and dendrite.
Contain organelles (e.g., ribosomes, some ER)

Dendritic Spine Structure

Contain abundant microfilaments (actin).
Lack microtubules and intermediate filaments.
Vary in shape, including thin, stubby, and mushroom-like, influencing synapse efficacy.

Dendritic Transport

Dendritic transport shares similarities with axonal transport; motor proteins (e.g., kinesin, dynein) along microtubules propel various components.
Dendrites are rich in microtubules.
Components such as receptors, lysosomes, etc., undergo anterograde and retrograde transport within the dendrites.

Summary

Neurones and brain cells exhibit significant diversity in their size, shape, function, neurotransmitter usage, and electrical activity.
Neuronal diversity reflects multifaceted control of communication.
Soma are a key site for protein synthesis and cellular processes.

Glia

Glial cells are the supporting cells of the Central Nervous System (CNS).
Glial cells comprise multiple types, including astrocytes, oligodendrocytes (Schwann cells within the periphery), microglia, ependymal, and radial glia.
A key ratio between glia and neurons is approximately 1-to-1.

Astrocytes

Form a substantial proportion (20-40%) in the brain; crucial for structural and metabolic functions.
Regulate ion homeostasis (primarily potassium).
Contribute to transmitter uptake and metabolism (glutamate, GABA, dopamine, etc.).
Release nutrients/lactate to provide energy (e.g., glycogenolysis & gluconeogenesis).
Interact with neurones and blood vessels extensively.
Play a role in neuroprotection; astrogliosis (reactive astrocytosis) is the adaptive cellular response to CNS damage.
Participate in signalling; associated with calcium waves.
Intertwined with blood vessels; critical to maintaining function.
Astrogliosis (neuronal dysfunction) arises from CNS issues.

Astrocytic Domains

Three dimensional reconstruction of astrocytes in a specific brain region (e.g., the dentate gyrus).
Reveals overlap between astrocytes and neurons (visual distinction from glial cells).

Metabolic Support (Astrocytes)

Participate in ion homeostasis and transmitter metabolism.
Support energy requirements of neurons (e.g., release of lactate from astrocytes to meet energy demands).
Crucial in energy homeostasis; release of neurotransmitter precursors into extracellular space.

Astrocytes & CNS Disorder

Proliferation and modification of astrocytes are associated with CNS damage.
Astrocytoma, a glioma, is the most frequent type of brain cancer in adults.

Astrogliosis

A protective reaction, initially beneficial, that may become maladaptive and contribute to neurological disorders if prolonged.
Triggered by many factors, including injuries such as trauma, strokes, diseases, and infections.

Astrocytes & Blood Vessels

Extensive contact between astrocytes (in particular, astrocytic end-feet) and blood vessels.
These contacts facilitate the exchange of nutrients and waste products between blood and brain tissue.
The end-feet wrap around blood vessels and maintain the integrity of the blood-brain barrier; this separation prevents immune cells and proteins from the blood from entering the brain unnecessarily.

Functional Hyperemia

Mechanisms in response to the brain's elevated energy demands.
Brain's ability to increase blood flow in response to elevated activity.
Signaling from neurons (via nitric oxide, NO), and astrocytes (e.g., phospholipase A2, PLA2) plays an important role in regulating blood flow.

Mechanisms of Vasomodulation

Illustration of the physiological processes involved in regulating blood flow in the brain. Mechanisms involve an astrocyte response triggered by changes in neuronal activity and oxygen availability, initiating signalling cascade to adjacent blood vessels, ultimately regulating their dilation and constriction.

Just Support Cells?

Astrocytes and other glial cells, in response to neurotransmitters, may regulate or conduct signals alongside neurons.

Astrocyte Signalling

Astrocytes communicate via connexin hemichannels; although not like a clear syncytium, astroglial cells may function independently in the brain.
Ca2+ waves (initially implicated by IP3 receptors) accompany neurotransmitter release and subsequent neuronal activation.

Astrocytic Calcium/Sodium Waves

Illustration of the calcium (Ca2+) and sodium (Na+) waves observed in astrocytes in response to a specific stimulus (e.g., glutamate).

Gliotransmission

Transmission between astrocytes and neurons involve the release of neurotransmitters, such as glutamate, D-serine, ATP, and adenosine from astrocytes.
ATP may trigger astrocytic Ca2+ wave responses in the brain.

Astrocytes & Synapses

Interactions between astrocytes and synapses play a critical role in synaptic function from their origin (in the retina).

Extrasynaptic Signalling

Slow inward and outward currents (SICs and SOCs) likely arise from astrocyte-mediated release of neurotransmitters (Glutamate, GABA) and result in neuron activation.
Astrocytic signals may influence neuronal synchronicity — the simultaneous activation of multiple neurons.

SICs & Neuronal Synchronisation

Large, slow inward currents in neurons, potentially driven by astrocytic gliotransmitter release.
Activation of NMDA receptors may involve these neuronal signals or currents.
Neuronal activation may occur across multiple neurons, even distant ones, influenced by glial signalling.

CNS Immune System

The unique "privileged" immune system in the CNS involves the separation from the peripheral system.
Separated by the blood-brain barrier (BBB).
Immune cells (e.g., microglia) play a crucial role in the CNS's immune response.

Microglia

Microglia are resident immune cells in the CNS.
Normally found in the ramified state, surveying the CNS for signs of damage, and in an activated state, exhibiting proliferation and an amoeboid form in response to activation.
Non-phagocytic phase characterised by soma enlargement and process shrinkage; phagocytic phase involves complete amoeboid transformation.

Microglia Activation

Microglia transform from a ramified shape to an activated ameboid morphology in response to various cues (e.g., damage).
Activated microglia can recruit additional immune cells across the blood-brain barrier (BBB) if necessary.

Microglial Immune Signalling

Activating triggers involve infection, injury, and neurodegenerative disorders.
Similar signalling molecules are used across diverse CNS immune cells.
Microglia respond to potentially damaging molecules like LPS, amyloid-beta, and others.
Inflammatory mediators (e.g., IL-1, IL-6, TNFα) are released.

Pathological Immune Responses

Chronic immune responses in the brain can become detrimental.
Associated with neurodegenerative disorders and epilepsy.
Release of cytotoxic molecules (e.g., ROS, glutamate) may lead to neuronal damage; exacerbated by recruitment from the peripheral immune system.

Oligodendrocytes

Responsible for myelin formation in axons of the CNS.
Pathology: multiple sclerosis leads to oligodendrocyte damage and demyelination.

Oligodendrocyte Myelination

Myelination process is regulated by electrical activity and other molecules.
Myelination is impacted by factors like axonal ATP release and various components of axonal membrane proteins (e.g., adhesion molecules).

Oligodendrocyte Pathologies

Oligodendrocytes are particularly susceptible to detrimental factors such as oxidative stress, high metabolic demand for myelination, iron concentration buildup, and low expression of antioxidant and associated receptors.
This vulnerability contributes to neurodegenerative/inflammatory damage.
Death from surrounding neuronal or astrocytic cells can contribute to damage and degeneration in oligodendrocytes.

Multiple Sclerosis

An immune-mediated CNS disorder characterized by inflammation and demyelination, culminating in neuronal damage.
Symptoms include muscle weakness, decreased coordination, sensory deficits, and autonomic disturbances.

Ependymal Cells

Line the ventricles of the brain and are rod-shaped and ciliated.
Crucial in the production and regulation of cerebrospinal fluid (CSF).

Radial Glia

Crucial during development; their role is in directing neuronal migration.
The progenitor cells facilitate proper architecture of the developing brain.

Other Glial Cells

Bergmann glia: cerebellar radial glia found in adults; act similarly to astrocytes.
Muller glia: retinal radial glia; perform similar roles as astrocytes.
Schwann cells: peripheral myelinating glia analogous to oligodendrocytes.
Satellite glia: support neurons in the autonomic ganglia.

Summary (Glia)

Astrocytes: provide metabolic and structural support, protection, and signalling.
Microglia: participate in the CNS's immune response.
Oligodendrocytes: essential for myelination.

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