Neuroscience - IS - lec1-5 - basics Flashcards
Soma
The central region of the neuron containing the nucleus. Also called the cell body.
Dendrite
Extend from the cell body to receive synaptic contacts from other neurons.
Axon
Most neurons have a single axon that carries signals to interconnected target cells and also provides a transport route to terminals
Synapse
Presynaptic membrane is closely apposed to the postsynaptic cell. ◻ Sites for interneuronal communication that contain specific proteins essential for transmitter release
Neurotransmitter
A chemical that is release from presynaptic terminal upon stimulation and activates postsynaptic receptors.
Receptors
A specialised protein that detects chemical signals and initiates a cellular response.
Glial cells
10-50x more abundant – neuroglia • astrocytes: mechanical support, growth factors • oligodendrocytes: myelin sheath • microglia: cf. macrophages • ependymal cells: lining of the ventricles a) structural support b) Schwann cells provide myelin c) Act as scavengers d) Buffer potassium and uptake of neurotransmitters e) Guide migration of neurons in development. f) Impermeable tight junctions, blood brain barrier g) Nutritive functions?? h) Communication & signalling role
Threshold for APs
APs are all or nothing events Occur only when the equilibrium potential is shifted so that the permeability of sodium is greater than potassium
Put the stages of an action potential in order and outline each: Hyperpolarisation, Threshold, depolarisation, depolarisation, Return to resting Em, Overshoot
Threshold - the equilibrium potential where enough voltage gated Na Channels ‘pop’ open so the PNa>Pk (^conductance ‘g’Na) Depolarisation - when the inside of the cell is negative there is a large force driving Na ions in Overshoot - where Em is greater than 0mV and approaches E Na Repolarisation - Voltage gated Na channels inactivate. Delayed opening of voltage gated K ions. K rushes out. - ^gK Hyperpolarisation - Undershoot Em goes towards Ek until K channels close Em returns to resting value determined by leak K.
What is the absolute refractory period and when does it occur?
The period of time measured from the onset of the action potential, during which another action potential cannot be triggered - Na+ channels inactivated - K+ channels open
What is the relative refractory period and when does it occur?
The period of time following an action potential during which more depolarising current is required to achieve threshold than normal - Some Na+ channels still inactivated - K+ channels open Need ↑ stimulus to overcome large gK i.e. threshold is higher)
What 2 factors does conduction velocity depend on?
- Diameter of axons (^=faster) 2. Myelination unmyelinated - 0.1 metres / sec myelinated - 100 metres / sec
What is saltatory Conduction?
Some axons have a myelin sheath (glial cell) wrapped around them that increases the speed of action potential transduction as it is now propagated between nodes of ranvier
What affects to local/regional anaesthetics have on nerves?
◻ Delay to threshold ◻ slow rate of rise of action potentials ◻ reduce rate of action potential conduction ◻ eventual failure of action potentials LAs inc; Cooling to low temperatures will block APs, ethanol, cocaine - initially discovered to cause numbing of the tongue used as a topical anaesthetic for opthamological surgery in 19th century.
TETRODOTOXIN
specifically blocks the pore of Na+ channels in the membranes of excitable cells. ■ Symptoms include: prickling or tingling of the mouth;diarrhoea; Numbness; Weakness; Hypotension; Rapid weak pulse; Respiratory distress/arrest; Death.
Scorpio Toxin
Increase the probability of sodium channel opening (open at lower threshold) and inhibit inactivation.
Describe the therapeutic action of local anaesthetics
Blocking Na channels should prevent pain, reduce cardiac arrhythmia and control convulsions. They are organic agents that reversibly block Na channels and therefore block nerve conduction
Phenytoin
is used in the control of epileptic convulsions other neurological disorders.
Side effects of local anaesthetics
■ Mainly on the CNS and CVS ■ Initially may cause CNS stimulation (euphoria with cocaine); restlessness, tremor and convulsions. ■ Later causes CNS depression with a risk of respiratory depression. ■ CVS effects: cardiac depression and vasodilatation with the possibility of severe falls in blood pressure.
An axodendritic synapse makes
connections from axon terminal to dendrites of neighbouring cell
An axosomatic synapse makes
axon terminal to soma of neighbouring cell
An axoaxonic synapse makes
axon terminal to axon of neighbouring cell
Asymmetrical synapses are
(grays type 1) - excitatory
Symmetrical synapses
(grays type II) - inhibitory
Convergence
when many presynaptic terminals from different cells connect to form synapses on a single postsynaptic neurone
Divergence
when a single presynaptic neurone forms many synaptic connections on different postsynaptic neurones
Name an excitatory neurotransmitter
Glutamate – most abundant excitatory neurotransmitter in the brain, present in all cells.
Name the inhibitory neurotransmitters the spinal cord
Glycine
How are amine and amino acid neurotransmitters synthesised, transported and stored?
GABA and the amines synthesised from metabolic precursors by enzymes in the terminal. AA and amines are concentrated in vesicles by transporters
How are peptide neurotransmitters synthesised, transported and stored?
Synthesized in rough ER and cleaved in the Golgi apparatus Secretory granules transported down axon to terminal by axoplasmic transport.
Put these stages of exocytosis NT release in order; ■ Fusion of synaptic vesicles with presynaptic membrane at the active zone. ■ The depolarisation opens voltage gated Ca2+ channels. ■ Contents are released into synaptic cleft. ■ Increased presynaptic [Ca2+]i. ■ AP invades the presynaptic terminal.
■ AP invades the presynaptic terminal. ■ The depolarisation opens voltage gated Ca2+ channels. ■ Increased presynaptic [Ca2+]i. ■ Fusion of synaptic vesicles with presynaptic membrane at the active zone. ■ Contents are released into synaptic cleft.
Describe how they work and give 2 examples of Transmitter gated ion channels
◻ Conformational change on transmitter binding allowing pore to open. ◻ Depolarising EPSP eg glutamate and Na+. ◻ Hyperpolarising IPSP eg GABA and Cl-.
What is a Quanta?
Smallest unit in which NT is released Number of quanta may vary but quantal size is fixed Quantal events are the building blocks of evoked synaptic potentials.
Define temporal summation
The summation of PSPs generated in rapid succession at the same synapse.
Define spacial summation
Summation of PSPs generated at more than one synapse on the same cell
What affects the effectiveness of an action potential triggering an EPSP?
In a passive dendrite membrane depolarisation falls exponentially with distance. - the distance of synapse from spike initiation zone. - properties of dendrite.
What is presynaptic modulation and how does it work?
■ Receptors on the presynaptic terminal may regulate the release of the neurotransmitter. ■ Activation of presynaptic receptor may hyperpolarise the presynaptic terminal so that APs cannot promote calcium influx. ■ By inhibiting calcium channels or activating potassium channels.
What are the 2 classes of presynaptic receptors:
Each of which can either be inhibitory of facilitatory, give some examples
◻ autoreceptors where the receptor recognises the transmitter that is released from that terminal
◻ heteroreceptors which recognise other transmitters which are different from that released by that terminal
Inhibitory autoreceptor - GABAb
Facilitatory autoreceptor - b2 (NADR)
Inhibitory heteroreceptor - H3 (histamine) D2 dopamine
Facilitatory heteroreceptor - angiotensin II, nicotinic ACh
Label this diagram:
- Action potentials arrive at the axon terminal
- Voltage gated calcium channels open
- Calcium enters the cell
- Calcium signals to vesicles
- Vesicles move to the membrane
- Docked vesicles release NT to the membrane by exocytosis
- Neurotransmitter diffuses across the synaptic cleft and binds to receptors
Describe electrical synapses
■ 3 nm gap spanned by connexons which form a pore.
■ Gap junctions.
■ Allow direct transfer of ionic current.
■ Brain development, neuronal synchrony.
Label this image of an axon
From top left round anticlockwise;
dendrites - the branching structure of a neuron that receives messages (attached to the cell body)
axon terminals - the hair-like ends of the axon
myelin sheath - the fatty substance that surrounds and protects some nerve fibers
axon - the long extension of a neuron that carries nerve impulses away from the body of the cell.
node of Ranvier - one of the many gaps in the myelin sheath - this is where the action potential occurs during saltatory conduction along the axon
Schwann’s cells - cells that produce myelin - they are located within the myelin sheath.
nucleus - the organelle in the cell body of the neuron that contains the genetic material of the cell
cell body - the cell body of the neuron; it contains the nucleus (also called the soma)
Where do alpha motor neurones recieve input from:
Upper motor neurones of the brain
sensory inputs from muscle spindles
spinal interneurones
- They are directly responsible for the generation of force from muscle
- Alpha motor neurone + muscle = motor unit.
- Alpha motor unit communicates with muscle fibre at the neuromuscular junction (NMJ).
Label diagram from top to bottom:
- Motor Neurone Axon
- Synaptic Folds
- Synaptic vesicles
- Post synaptic receptors on muscle plasma membrane
5 Mitochondrion within muscle (motor) end plate
Outline the role of calcium in neurotransmitter release (at the NMJ)
Depolarisation during AP in presynaptic terminal opens voltage-gated Ca 2+ channels (i.e. ↑ PCa)
Ca2+ enters nerve terminal down electrochemical gradient
Fusion of vesicles with presynaptic membrane - Acetylcholine (ACh) released!
Outline the role of acetylcholine in generating the end-plate potential (excitatory postsynaptic potential)
The Em of a muscle cell is about -90mV
ACh binds to receptor (nicotinic AChR) on postsynaptic membrane (end-plate)
- ligand-gated ion channel
Opening of channel permeable to Na+ and K+
Na+ influx > K+ efflux
Depolarisation of end-plate to −20 mV
Features of end-plate potentials
Time from pre-synaptic AP to EPP < 1 msec
EPP generated by ligand-gated channels
→ opening voltage-gated channels (generate AP)
EPP is very large compared to other EPSPs (high density of nAChRs)
Threshold for AP generation easily passed
(high density of voltage-gated Na+ channels at end-plate)
What are the 5 subunits of a nicotinic acetylcholine receptor and to which does ACh bind?
2 alpha to which ACh binds
1 beta
1 y gamma
1 d delta
What is Myaesthenia Gravis?
Autoimmune disease - get the generation of antibodies against nACh receptors. These bind to receptors interfering with normal function and leading to degeneration of the NMJ.
Effective treatment involves inhibition of AChE prolonging the lifetime of released ACh e.g. neostigmine
