lecture 2 - Cells of the Nervous system Flashcards
the neurone
Four functional regions:
Input
Integrative
Conductive
Output
Most but not all neurons share all these features:
* Local interneurons often lack a conductive component
Input:
Electrical signal, integral to the cell
Integrative
Electrical signal, integral to the cell
Conductive:
Electrical signal, integral to the cell
Output
Chemical signal, where the chemical substance is ejected by the cell into the
synaptic cleft.
The neuron – morphological
variation - Identify the dendrites, axon and cell body
Classifying neurons based on
morphology
Neurons can be classified as unipolar, bipolar or multipolar based on the number
of processes that originate from the cell body
Neurons can be classified
based on:
Morphology
* Major functional categories
- Sensory neuron
- Motor neuron
- Interneuron:
- Relay
- Local
* Physiology
* Neurotransmitter
* Gene expression profile
* Location
Classifying neurons table
Glial cells
Astrocytes
- Astrocytes are star-shaped glia found in all areas of the brain.
- They constitute nearly half the number of brain cells.
- They have large numbers of thin processes that enfold all the blood vessels of the brain, and
ensheath synapses or groups of synapses.
By their physical association with synapses and blood vessels, they play key roles in: - Nourishing neurons
- BBB.
Blood-brain barrier
- A key structure protecting the brain from systemic insults
- The BBB is formed by:
1. Endothelial cells (EC), which are interconnected by very complex interendothelial tight junctions
2. Pericytes (PC), smooth muscle-like cells.
3. Astrocytic projections called endfeet (AE). - The BBB tightly regulates the movement of ions, molecules, and cells between the blood and the brain, which is essential for neuronal homeostasis and protects the brain tissue from toxins and pathogens.
- Astrocytes take up glucose from the circulation and deliver energy substrates to
neurons.
Tri-partite synapse
- Astrocytes extend their processes to surround the synaptic connection between two neurons, forming a tripartite synapse
- Using high-affinity transport channels, they rapidly uptake released neurotransmitters
- The neurotransmitters are then converted, and the end-product is transferred back to neurons
- High concentration of extracellular
neurotransmitters can lead to excitotoxicity, and the death of neurons. - Astrocytes can also release gliotransmitters to modulate synaptic signalling.
Astrocytes
By their physical association with synapses and blood vessels, they play key roles in:
- Nourishing neurons
- BBB.
- Regulating extra-cellular concentrations of ions, neurotransmitters and other molecules.
- K+ buffering
- Accumulation of Cl- ions and water.
- Neurotransmitter recycling.
- Modulating synaptic signaling.
- The astrocyte network is thought to modulate nearby neuronal activity by triggering the release of nutrients
and regulating blood flow. - The development of synapses.
- Astrocytes release neurotrophic and gliotrophic factors that promote the development and survival of neurons and oligodendrocytes
Two glial cells responsible for myelination:
- Oligodendrocytes in the CNS
- Schwann cells in the PNS
- Allows for the rapid conduction of electrical signals along
the axon - These cells produce thin sheets of myelin that wrap
concentrically, many times, around segments of
axons. - One Schwann cell produces a single myelin sheath for one
segment of one axon - One oligodendrocyte produces myelin sheaths for
segments of as many as 30 axons
Myelinating Glial Cells
- Oligodendrocytes and Schwann cells produce myelin only for segments of axons.
- The regularly spaced segments of the myelin sheath can differ in length and/or size, providing individual neurons with unique myelin profiles.
- These segments are separated by ∼1 µm unmyelinated gaps called nodes of Ranvier, where the plasma membrane of the axon is exposed to the extracellular space.
- Nodes have a high density of Na+ channels.
Myelin and Conduction
- Myelination increases the speed of conduction (saltatory conduction) and prevents the action potential from decaying, allowing it to travel over long distances.
- The number of myelin layers on an axon is proportional to the diameter of the axon.
- Larger axons have thicker sheaths, while very small-diameter axons are not myelinated.
- Nonmyelinated axons conduct action potentials much more slowly due to their smaller diameter and lack of myelin insulation.
Microglia - Origin & Function
- Unlike neurons, astrocytes, and oligodendrocytes, microglia derive from the bone marrow and enter the CNS early in development.
- Their morphology is non-uniform and changes depending on the physiological or pathological context.
- The most characteristic feature of microglial cells is their rapid activation in response to environmental changes in the CNS.
Microglia - Immune & Synaptic Roles
- Of all the cells of the CNS, microglia are the best at processing and presenting antigens to lymphocytes and secreting cytokines and chemokines during inflammation.
- Thus, they bring immune cells to the CNS.
- They can also become macrophages and clear debris in the CNS.
- They actively participate in the modulation of neuronal function by regulating synaptic pruning in both physiologic and pathologic processes.
Choroid plexus and ependymal cells
- All ventricles of the brain are lined with the ependyma, a single layer of
ciliated cuboidal cells - Ependyma helps move cerebrospinal fluid (CSF) through the ventricular
system. - The CSF is produced by the choroid plexus epithelial cells. It encases the brain
and provides nourishment, protein and ion homeostasis as well as protects the
brain from physical trauma.
Satellite glial cells
- Satellite glial cells (SGCs) wrap around neuronal cell bodies, in most cases forming a complete
envelope. - SGCs are found exclusively in peripheral ganglia — sensory, parasympathetic and sympathetic
ganglia - The close contact between SGCs and neurons enables them to control neuronal homeostasis, but
very little is known on this topic. - SGCs express K+ channels and glutamate transporters → Probably control glutamate and K+ levels at synapses.
What are model organisms?
- A model organism is a specie that has been
widely studied, usually because it is easy to
maintain and breed in a laboratory setting
and has particular experimental
advantages - Help understand fundamental mechanisms applicable to more complex systems, including humans.
What should an ideal model provide the
researcher?
- Accurately mimic the desired function or disease
- Data extrapolatable to man
- Species availability
- Be available to multiple investigators
- Be handled easily by most investigators
- Survive long enough to be functional
- Fit available animal housing facilities
- Be of sufficient size to provide multiple samples
Be polytococous (multiparous) so that multiple offspring
are produced for each gestation
- Be of sufficient size to provide multiple samples
- Ethically approved for use
Data extrapolatable to man
Extrapolatable refers to the ability to infer the unknown from the known: predict human data by relying on
animal data.
Two main characteristics: fidelity and discrimination
* Fidelity is how close a model is to the organism or condition we are studying in our target species.
* Discrimination means the extent to which the model reproduces one particular propertyof the original, in
which we happen to be interested.
Mammal model: Rodents
Mouse Mus Musculus
Rat Ratus Norvegicus
Mus musculus is the experimental model organism that permits the most diverse strategies
of assessing the role of specific genes and the phenotypic manifestation of genetic
variation in mammals.
In rats, genetic modifications are more difficult to perform however they are particularly
useful in the study of complex behaviours (stress, anxiety, depression, aggressivity,
learning..)
Advantages:
- Complex behaviours
- Organs homologous to humans
- Genetic similarity to humans
Limitations:
- Very expensive husbandry costs
- Experimental cycle long
- Ethical constraint
non mammalian vertebrate model: Danio Rerio
Zebrafish Danio Rerio
One reason that zebrafish are an important biomedical model is because zebrafish embryos are
transparent and develop outside of the uterus. This unique developmental process allows scientists to study
the details of development starting from fertilization and continuing throughout development
Advantages:
- High reproductive rate
- Development is external
- Genetic similarity to humans
- Embryos and larvae are
transparent
- Possibility to study complex
behaviours
Limitations:
- Moderate predictivity
- Moderate translational value
Invertebrate model: Drosophila Melanogaster
Fruit Fly Drosophila Melanogaster
Drosophila has been used productively as a model organism for over a
century to study a diverse range of biological processes including
genetics and inheritance, embryonic development, learning, behaviour,
and aging.
Advantages:
- Easy to work with
- Short generation time (10days from fertilized egg to adult)
- Low cost of maintenance
- Small genome, 4 chromosomes
- Useful model to study behaviours such as aggression, sex drive,
motivation and insomnia
Limitations:
- Genetically distant from humans
- Relatively simple anatomy (100000 neurons, also an advantage!)
- No adaptive immune system
Non-human primates
Non-human primates are better positioned to provide relevant translational information because
of their higher brain complexity and homology to humans.
However, among others, lack of resources and formal training, strict legislation, and ethical issues
impede broad access to large animals.
Ethical Considerations : The 3 Rs
The 3Rs are principles of good science designed by scientists to improve animal welfare
and scientific accuracy.
What about in vitro models?
They differ in terms of:
* Their architecture and dimension, (2D or
3D)
* The absence of scaffolds for spheroids and
organoids
* The presence of biomaterials
representative for scaffold-based cultures
* The compartmentalization of the cells
culture
* Presence of physical and chemical cues such
as fluid flow offered by microfluidic devices.
What about in vitro models?
What about in vitro models?
