Introduction to cellular neuroscience Flashcards
What is the goal of cellular neuroscience
Understand how the nervous system works from a bottom up approach, starting from a knowledge of cellular structure and physiology , leading to knowledge of systems and how they work together to underpin cognitive functions
What is the hardware of the nervous system
ie cells- constrain how the system mediates behaviour and function
What does the nervous system do
Coordinates physiology and behavior through 3 principle processes- sensation, integration and action
Nervous system principle processes- sensation
Gathering info about the internal (happy, hungry) and external environment (threat, surroundings)
Nervous system principle processes-integration
Determining appropriate response based on multisensory info (different representatinos of internal/external environment) and past experience
Nervous system principle processes-response
Conveying coordinated signals from CNS to the muscles and glands
Why do multicellular organisms need a nervous system
For fast long-range communication
What are nerves
Bundles of fibres emanating from the brain and central cord that branch repeatedly to innervate every body part,, and carry info from senses into CNS to effector organs to enact motor responses
What does the nervous system include in vertebrates
The brain, spinal cord, nerves and sense organs
What are the 2 defining features of neurons
Electrical excitability (can emit fast, electrical impulses), formation of synapses
What cells in the body other than neurons can show excitability
Cells in the heart and muscles
What do synapses do
Connect neurons, convert an electrical signal into a chemical signal to an electric signal, for fast intercellular communication
What are the typical features of neurons
Dendritic arbours, soma, axon,
What are dendrites
Provide the major site for convergent synaptic input from other neurons, and propagate the signal all the way down to the common branch
How does the no of synaptic inputs received by each neuron differ
Varies from about 1-100,000
No of inputs a neuron receives is reflected in the complexity of its dendritic arbor
What is the soma
Cell body- contains machinery for translating and transcribing proteins (nucleus, ER, ribosomes, Golgi), mitochondria for generating energy stores and other organelles essential for cellular function
Integrates dendritic inputs
Where are dendritic inputs integrates
Soma
What does the axon do
Generates and propagates fast electrical impulses to targets, can branch to contact multiple postsynaptic cells
Output cables of neurons
How long can axons be
Can be up to several m in length to transfer info over long distances
What is the nervous system defined by
The presence of neurons which form synaptic connections for high speed communication
Examples of cells specialised for transduction of sensory stimuli
Hair cells in auditory and vestibular systems
Photoreceptors in the retina
Merkel cells in the skin
What does the estimated ratio of glia to neurons in the nervous system vary from
100:1 to around 1:1
What types of glia cells are in the CNS
Astrocytes, ependymal cells, oligodendrocytes, microglia
What type of glia cells are in the PNS
Satellite cells, Schwann cells
What do glia play key roles in
Development, maintaining and supporting neural activity, pathogenesis of neurological disorders
Where are ependymal cells located
Line the ventricles and central canal of the spinal cord
What do ependymal cells do
Have beating cilia that direct movement of cerebral spinal fluid- cushions against shock to skull and spinal cord, washes away waste products, delivers metabolised ions
What is the result of issues with ependymal cell function
Disturbances in the flow of cerebral spinal fluid leads to hydroencephaly (build up of water in the brain, extra pressure can be very damaging)
What do astrocytes and satellite cells do
Regulate the external chemical and physical environment of neurons
Astrocytes fill most of the space between neurons
What functions do astrocytes carry out to regulate the external chemical and physical environment of neurons
Ionic homeostasis, neurovascular coupling, maintaining synaptic functioning
How do astrocytes control ionic homeostasis
Regulate the ionic concentration of extracellular sites around neurons via connections that allow molecules taken in by one astrocyte to diffuse to another
How do astrocytes control neurovascular coupling
Link between brain activity and blood flow to that region, can cause blood vessels to dilate to increase oxygen supply
How do astrocytes maintain synaptic function
End feet wrap around synaptic junctions that regulate what happens to the transmitters once they’re released from the presynaptic neuron, restricting the extracellular space
What do oligodendrocytes and Schwann cells do
Generate and maintain the myelin sheath that surround and insulate axons to allow high speed conduction of action potentials
How do oligodendrocytes and Schwann cells differ
Oligodendrocytes- CNS, provide mylination for many axons
Schwann cells- PNS, only wrap around one axon
What are microglia
Immune effector phagocytic cells of the CNS- become active and destroy any invading agent
Clear away dead cells and remodel synapses during development
Why are microglia largely inactive under normal physiological conditions
CNS is very well protected by the blood brain barrier from invading agents
What directly underlies fast and adaptive behaviour
High speed communication in neuronal networks
What do glia do for the neurons they surround
Insulate, support and nourish them
What is Nissl stain
Stains clumps of material surrounding neuron nuclei called Nissl bodies, useful distinguishing neurons and glia (neurons have more RER), allow study of the neuronal arrangement in the brain
What is Golgi stain
Makes a small percentage of neurons entire;y darkly covered
What can axons and dendrites both be classified as types of
Neurites- thin tubes extending from the soma
What is the neuron doctrine
Cajal- follows cell theory that the individual cell is the elementary functional unit of all animal tissues, neurites are not continuous but communicate by contact
What is reticular theory
Golgi- the brain is an exception to cell theory, neurites of different cells are fused together to form a continuous reticulum
When was the neuron doctrine vs reticular theory conflict solved
The increased resolving power of the electron microscope in the 1950s revealed the neuron doctrine was correct- neurites are within 0.02um of each other
What is the diameter of the soma
About 20um
What is the cytoplasm
Refers to everything within the cell membrane including organelles excluding the nucleus
How do the ribosomes on the RER gives neurons their information-processing abilitiies
They produce special membrane proteins
What do different sections of the SER do
Some fold proteins that jut out from the RER, some regulate the internal concentration of substances like calcium
What is the Golgi apparatus’ role
Sorting proteins for delivery to different parts of the neuron eg axon and dendrites
What do mitochondria do
Pull inside pyruvic acid and oxygen from the cytosol, Krebs cycle produces energy that via the electron transport chain along the cristae results in ADP + P -> ATP
How many ATP molecules are released for every model of pyruvic acid taken in by the mitochondria
17 ATP molecules
How thick is the neuronal membrane
5nm thick
How does the membrane’s protein composition vary across location
Varies depending on whether it is the soma, dendrites or axon
What does the cytoskeleton consist of
Microtubules, microfilaments and neurofilaments
What are the diameter of microtubules, microfilaments and neurofilaments
Microfilaments- 5nm
Neurofilamets- 10nm
Microtubules- 20nm
What do microtubules do
Polymerisation/depolymerisation of microtubules and hence neuronal shape can be regulated by signals in the neuron
What regulates the assembly and function of microtubules
Microtubule associated proteins (MAPS)
What do microfilaments do
Involved in changing cell shape, especially numerous in the neurites
What do neurofilaments do
Very mechanically strong, resemble the bones and ligaments of the skeleton
What are the different segments of the axon called
Axon hillock forms initial segment of axon branching off from the soma, middle section is axon proper, end of axon is the axon terminal
Rough ER in axon vs soma?
No rough ER extends into the axon, so all axon proteins produced by protein synthesis originate in the soma- axons cannot be sustained without the cell body providing proteins
Ribosomes in axon vs soma
Mature axons contain few free ribosomes, so no protein synthesis and all axon proteins are made in the soma
Why does protein composition of the axon membrane differ from the soma membrane
Allows the axon to act as a wire sending info over long distances
What are axon collaterals
Axon branches that return to communicate with the same cell they branched
What are recurrent collaterals
Axon branches that return to communicate with dendrites of neighbouring cells
What does the axon terminal do
Branches out to other synapses to form the terminal arbor
Can also form synapses at boutons en passant than terminate elsewhere
Forms synapses with other cells to provide innervation
How does the axon terminal cytoplasm differ from axon cytoplasm
Microtubules don’t extend into terminal
Contains synaptic vesicles, small bubbles of membrane
Inside surface of the terminal membrane facing the synapse has a dense covering of proteins
Numerous mitochondria indicating high energy demand
What is the synaptic cleft
The space between the presynaptic and postsynaptic membrane
What does a synapse consist of
Presynaptic and postsynaptic membrane, synaptic cleft
What is axoplasmic transport
Flow of materials from the soma to the axon terminal
Who demonstrated slow axoplasmic transport
Weiss in 1940s- tying off an axon led to material building up on the soma side of the knot, when untied material moved down the axon at 1-10mm a day
How was fast axoplasmic transport shown
Seen in 1960s- by tracking the movement of radioactive amino acids injected into neuron somata as they were assembled into radioactive proteins and travelled to the axon terminal, rate of transport found to be 200-400mm a day
What is anterograde transport
Movement of material from the soma to the terminal by kinesin
What is retrograde transport
Movement of material up the axon from terminal to soma using dynein
How is anterograde transport carried out
Vesicles carrying material ‘walk down’ the axon’s microtubules to the terminal, using kinesin ‘legs’ fuelled by ATP
How is retrograde transport carried out
Material is moved up the axon from the terminal to the soma using dynein ‘legs’
What is thought to be the goal of retrograde transport
Thought to provide signals to the soma about changes in the axon terminal’s metabolic needs
What study shows the need for axons to be provided proteins by their soma
Wallerian degeneration- the degeneration of axons when they are cut, shown by Waller in mid-19th century
What are dendritic spines
Some dendrites have dendritic spines on them that receive synaptic input- thought to isolate various chemical reactions triggered by some types of synaptic activation, their structure thought to be sensitive to the type/amount of synaptic activity
Study showing the importance of dendritic spines
Padilla et al (1974)- intellectually disabled children had fewer dendritic spines, or unusually long and thin dendritic spines, with extent of change correlated with degree of intellectual disability
Classification of neurons by number of neurites
Unipolar, bipolar, multipolar (most neurons in the brain)
Classification of neurons by dendrites
Dendritic arbors vary widely across different types of neurons eg cerebral cortex contains 2 broad classes (stellate and pyramidal cells), spiny vs aspinous
Classification of neurons by connections
Primary sensory neurons- have neurites in sensory surfaces
Motor neurons-form synapses with muscles
Interneurons- form connections with other neurons only (most of nervous system)
Classification of neurons by axon length
Golgi type I/projection neurons extend beyond brain areas via long axons, Golgi type II/local circuit neurons have short axons that don’t extend beyond the cell body vicinity
What are most differences between neurons explainable by
Explainable at the genetic level eg different gene expression -> different shapes of pyrimidal and stellate cells
How can transgenic mice allow investigation of neurons in a genetic class
eg green fluorescent protein (GFP) is commonly used as allows visualisation of the neuron it is expressed in when illuminated with the appropriate wavelength
What leads to differences in the neurotransmitter used by a neuron
Differences in the expression of proteins involved in transmitter synthesis, storage and use
Classification of neurons based on neurotransmitters
eg motor neurons used in voluntary movemet release acetylcholine so are cholinergic (express the genes that enable use of this particular neurotransmitter)
What is the resting membrane potential of astrocytes
Negative
What is in astrocytic membranes
Neurotransmitter receptors that can trigger electric and biochemical events inside the cell
What are the nodes of Ranvier
Short exposed sections of the axonal membrane where there are periodic gaps in the myelin sheath
What is vasculature in the brain
Arteries/veins/capillaries that deliver essential minerals and oxygen to neurons via the blood
What are the 3 main groups of transmitters
Amino acids, amines, peptides
What does the brain turn into what
Turns patterns of stimulation (S) into patterns of response (R)
How are patterns of stimulation turned into patterns of response in the brain
A pattern of of energy at one neuronal level is transformed into a different pattern in the next, meaning S is modified as it is transmitted across the levels, until it becomes a completely different pattern as R
What does each neuron on each neuronal level in the brain only respond to
A particular pattern of activity aong the neurons on the level immediately above it
What is the blood brain barrier
The tight junctions (no pores) held between astrocytes that separate neurons from cerebral capillaries, a highly selective border lining blood vessels
What is the plasma membrane of the axon called
The axolemma
What is the difference in location of boutons on motor neurons vs sensory neurons
Sensory neurons have few presynaptic boutons on its cell body or axons, whereas motor neurons have 95% of their boutons on their dendrtitic branches
How is the myelin sheath arranged
Arranged in concentric layers of membrane, with lipid layers interspersed with protein layers
70% lipid, 30% protein
What are genes in Schwann cells vs oligodendrocytes
that encode myelin turned on by
Schwann cell- presence of axons
Oligodendrocytes- presence of astrocytes
How does MS demonstrate the importance of myelin
MS is a demyelinating disease, involves problems with sensation and movement because the transmission of nerve signals is slowed causing problems with sensory perception and proper motor coordination
Mice demonstration of the importance of myelin
Mice with the shiverer (shi) mutatino have greatly deficient myelination in the CNS, leading to tremors, convulsions and early death
