Microanatomy of the nervous system Flashcards
Why did Santiago Ramon y Cajal and Camillo Golgi were jointly awarded the Nobel Prize of physiology and medicine in 1906?
For their discovery that the brain is not a single continuous system, but composed of individual cell units
We now know those are Neurons and supporting glial sub-types
How Neurons communicate?
What makes the different types of neurons?
What are these types?
Neurons communicate by passing electrical signals along their elongated form and then converting these into chemical signal to activate an electrical signal in the next neuron
Many forms of neurons specialised for their particular function within the nervous system
- Model neuron: receives signals from / sends signals to other neurons and has a long extended shape
- Sensory neurons: can be activated by changes in skin cells
- Motor neurons: stimulate muscle movement
- Local interneurons: send and receive signals with multiple other neurons
What are the glial subtypes?
- Astrocytes
- Microglia
- Oligodendrocytes
- Ependymal cells
What is the role of ependymal cells?
Line the ventricles of the brain and the central canal of the spinal cord.
What is the relation between neurons and glial cells?
Neurons are supported by different types of glia.
What is the role of astrocytes?
- Physical scaffolding framework for neurons
- Distribute nutrients from the blood supply to neurons
- Help maintain blood-brain barrier
- Tissue repair -> glial scars
- Regulation of synaptic activity by direct contact with synapses (tripartite synapse)
- Astrocyte-astrocyte signalling via gap junctions
- Help maintain optimal microenvironment around neurons
- potassium (K) buffer after depolarisation
- metabolize and recycle NTs: especially Glu (toxic extracellularly)
What is the role of microglia?
- Smaller than the astrocytes (as per name)
- CNS macrophages
- Resident immune cells of brain = immunosuppressed stable population
- Clear cellular debris -> degrade synapses
- essential for synaptic pruning during development, BUT makes matters worse by preventing recovery when neurons undergo chronic stress during disease
- apoptosis
- Recruit other cells to sites of damage
- assist activated T cells
- Aid in tissue repair
What are macrophages?
Primary mediators of granulomatous inflammation
- M1 macrophages are activated for cell mediated immune response to provide host defence
What are T cells?
T cells are central regulators of the immune response
- modulate the function of other immune cells
- affect the behaviour of endothelial and parenchymal cells
- express membrane-bound molecules and secrete soluble mediators -> control antibody responses, activate innate immune cells, and lyse target cells
What is the role of oligodendrocytes?
- Support and insulate neuronal axons by generation of myelin sheath in CNS (vs. Schwann cells in PNS)
- increased speed of neuronal signaling through saltatory conduction
- Provide metabolic support to neurons (aided by their proximity)
What is the difference between oligodendrocytes and Schwann cells?
> Oligodendrocytes form myelin sheath on neuronal axons in the Central Nervous System (CNS)
> Schwann cells form myelin sheath on neuronal axons in the Peripheral Nervous System (PNS)
What is the impact of demyelinating diseases, such as multiple sclerosis?
Cause degeneration of the myelin sheath, which prevents the brain from communicating properly with the body.
What is characteristic of the difference between acute and chronic neuroinflammation?
There is a delicate balance between:
- an Acute neuroinflammation inducing a defence response,
- and a Chronic neuroinflammation inducing an over/aberrant activation of astrocytes and microglia
Altered function of glial cells -> disturbed synaptic transmission
=> Dysfunction can result in vulnerability to neurodevelopment and neurodegenerative diseases
What does the extent of dendritic branching reflect?
The neurone’s required level of input: dendrites are the main site of neuronal input
What does axonal length determine?
Which neurons have long axons?
The distance of ouput in the network: motor neurons have long axons
e.g. longest axon from lower motor neuron cell body in spinal cord to control the muscles in your big toe = 1m
What are dendritic spines?
Small protrusions on dendrites which form the postsynaptic side of a synapse, receiving input from another neuron
- their shape and size will affect the receive and transmit input
- spines with larger surface area form stronger, more stable synapses
- spines are ‘plastic’: increase in size during learning and memory
What is characteristic of microglial morphology?
Microglial change morphology when they become activated or ‘reactive’:
- progressively become round and phagocytic
- reactive microglia release more cytokine to attract more microglia to the site of perceived injury
- in phagocytic mode, they consume any perceived debris, which can include synapses
Morphology can be used to score and infer neuroinflamation
What is a phagocyte?
Type of cell with ability to ingest and digest foreign particles (e.g. bacteria, dust, dye)
What are cytokines?
Polypeptides secreted by leukocytes and other cells that act principally on hematopoietic cells
- the effects of which include modulation of immune and inflammatory responses
- their concentrations vary during the course of a disease
- pro- or anti-inflammatory effects, and these effects can be contextual
What is characteristic of astrocytic morphology?
What is astrocytosis?
Astrocytic morphology is highly variable, even at rest
Activation is therefore often inferred through astrocytosis: an increased number of cells in a given location (due to recruitment or proliferation of astrocytes)
How can microglial and astrocytic morphologies be used?
To score and infer neuroinflammation (Ghazi-Noori et al., 2012):
> the mouse model of frontotemporal dementia shows progressive neuroinflammation (vs. non-transgenic mouse control) when stained with anti-microglial (Iba1) antibody
> Increased coverage of staining for an astrocytic marker (GFAP) infers astrocytosis in a mouse model of frontotemporal dementia (vs. non-transgenic mouse control)
What is common of all cells? What are the 2 broad categories of cells?
All cells have a cell membrane, a cytoplasm (belly fluid), and DNA
- Eukaryotic cells
- they have a nucleus and membrane-enclosed organelles (‘little organs’)
- they are complex cells found in plants and animals
(e. g. neurons) - Procaryotic cells -> unicellular organisms (e.g. bacteria)
- no nucleus or membrane-enclosed organelles
- they have DNA, but not contained in a nucleus
What are the neuronal substructures (organelles)?
- Nucleus - genetic information store
- Endoplasmic reticulum - proteins produced, sorted and processed for delivery to their required location
- Golgi apparatus - additional sorting and processing centre
- Mitochondria - energy generator (synthesise ATP molecules for energy); also has roles in calcium buffering and cell signaling)
- Lysosome - degrades proteins and organelles when faulty; “garbage collectors”: filled with enzymes that breakdown cellular debris
- Cell membrane - lipid bilayer containing receptors for cellular communication
What are the two types of endoplasmic reticulum?
What is its function?
- Rough endoplasmic reticulum (rER): with ribosomes
- Smooth endoplasmic reticulum (sER): no ribosomes
- Produce proteins, sort and process them for delivery to their required location