FOUNDATIONS: FUNCTION OF NERVOUS SYSTEM Flashcards
What is the absolute refractory period?
Minimum time it takes for the action potential to be generated
What are channel rhodopsins?
Membrane channels that allow neurons to be excited by light
What is channel rhodopsin-2 opened by and where did it come from originally?
Comes from green algae and opens (depolarises) in response to blue light (BLUE #2)
What is halorhodopsin (NpHr) activated by and where did it originate from?
Comes from prokaryotic archaea bacterium (African Salt Lakes) and is activated by yellow light. When yellow light is shone, Cl- is pumped INTO the cell so that it HYPERPOLARISES (EVEN WHEN [CL-] INSIDE CELL IS HIGHER- against conc. gradient)
What is the purpose of optogenetics?
To see how different regions of the brain work and if behaviour changes in parts of the brain
How does the process of optogenetics work?
- genes cloned NpHR and Rhodopsin-2
- Then transfected into cells via a viral vector
- Genes linked to channel specific promoter active only in certain cells like neurons
- Viral vector injected into region of brain so neurons in that region take in Rhodopsin or NpHR and express either of them
- transfected cells glow green and GFP gene is bound to ch2 or NpHr gene
What happens to neuron if the NpHr gene is present?
- ## It will be INHIBITED by yellow light due to hyperpolarisation (Cl- influx into the cell irrespective of intracelular concentration)
What happens to neurons if the Rh-2 gene is present?
Neuron will be ACTIVATED by blue light and will DEPOLARISE causing an ACTION POTENTIAL
What is the function of general glia?
Support neuronal function
What do Oligodendria and Schwann cells do and what are they?
Oligodendria are in the CNS and Schwann cells are in the PNS
- Generate myelin which increases axonal conduction velocity
What do astrocytes do and where are they found ?
- most numerous and diverse in the brain
- Supports synaptic signalling
- Fill spaces between neurons and vessels
- Influence neurite growth
- K+ buffering
- Metabolic support for neurons
- maintain blood brain barrier
How do astrocytes regulate chemical content?
- Removing neurotransmitter in the synaptic cleft
- Releasing modulatory substances and ensurer a good neurotransmission
What is the function of microglia?
They are the garbage system
- remove debris with dead cells
- fight inflammation
What do ependymal cells do?
They LINE the ventricles (lateral ventricles)
- produce CSF
- control fluid release between brain tissue and CSF in ventricles
- Form choroid plexus
Why are aquaporins important?
For things like Edemas (build up of fluids), Hydrocephallis (water on the brain) and critical for maintaining correct ionic concentration
What does it mean to be in equilibrium in the context of mempot?
Concentration gradient balances out the electric field
In the NERST equation, what is the equilibrium potential independent of?
Permeability and ionic conductance
What is the ionic equilibrium potential?
Voltage across membrane that counteracts movement of ions due to its concentration gradient
In context of GHJK equation, what determines permeability of membrane?
The density of channels
What maintains the resting membrane potential?
The |
- ATP pump!
What does the Na/k-ATP pump do?
Pushes sodium out of the cell and potassium in (both against concentration gradients)
Is the Na/K- ATP pump active all the time?
YES! Because it must maintain the ion concentraitons and continue to try and get the membrane back to restinf concnetrations
What are the 5 steps of the ATP Na/K-ATP pump?
- Open on inside of cell, pump binds ATP and 3 Na+ ions from inside
- ATP hydrolysed then pump is phosphorylated and ADP released
- Phosphorylation changes conformation releasing Na+ ions to extracellular space
- Pump then binds 2 K+ ions OUTSIDE CELL then dephosphorylation occurs and a SECOND CONFROMATIONAL change
- ATP binds and K+ ions released
What are K2P channels?
2 pore loop domains that are always open so they ‘leak’ K+
Has a high permeability to potassium at rest
What are Kv channels?
Voltage gated potassium channels
- open state depends on mempot
- normally closed and a common drug target
What are Nav channels?
Voltage gated sodium channels
- Open when membrane potential depolarises
What happens at -65mV in terms of Nav channel?
Channel is closed
What happens at -40mV in terms of Nav channels?
Channels open for 1ms and Na+ comes in
What does the inactivation stage involve for Nav channels?
The open pore is blocked by a globular portion of protein
What occurs in the reactiviation stage with regards to Nav channels?
Channels REACTIVIATE so globular protein unblocks channel but the channel still remains closed
As you increase the permeability to sodium ions,….
you move closer to + 62 mV
As you increase permeability to potassium ions….
You move clsoer to -80mV
What are Kv channels also known as?
Delayed rectifier channels - because they return the mempot to resting membrane level and they also take some time to open
What is the difference between absolute permeability and relative permeability?
ABSOLUTE permeability is the number of channels open within a membrane and the RELATIVE PERMEABILITY is the permeability of potassium relative to the permeability of sodium e.g. AT REST the relative membrane perm. of potassium is much higher than sodium.
In the resting state, what are the typical permeabilities of K+ and Na+?
Low perm. to Na+ and high perm to K+
In the open channel state, what are the typical permabilities?
Extremely high RELATIVE PERMEABILITY to Na+
Low relative permeability to K+
What is a signal?
A change in voltage (deviatons in the resting potential)
What is passive communication?
- no additional energy is put in
- diffusion of ions through cytosol (like in dendrites)
- ## not a reliable form of signalling
What is active signalling ?
-requires energy but AP propagates much better
What factor in neurons determines the WAY that they encode information?
THE RATE OF APs e.g. Retinal ganglion cells encode colour such as a high rate of APs for green stimulus
What does the membrane potential move towards when threshold is reached?
The Na equilibrium potential
What causes initial depolarisation?
PHYSICALLY gated Na_ channels can open from stretch sensitive Na channels in skin
OR depolarisation can be from somewhere else in the neuron or from another neuron
What causes the mempot to decrease after the overshoot?
K2P leak channels
What causes the undershoot in the AP?
Kv (voltage gated K+ channels)
Are APs all uniform?
NO!! Channel openings are stochastic (random) and can’t predict how many Na+ will move through each channel - it only looks uniform because there are thousands of channels together
What is the driving force?
Difference between the REAL membrane potential and the equilibrium potential
Where does the initiation of the AP start?
At the axon hillock
What is the axon hillock?
Also known as the ‘spike initiation zone’
- Region of the axon close to the cell body that has the HIGHEST DENSITY OF NAV channels
Why does an AP travel in only one direction?
Because the inactivated Nav channels prevent back propagation of AP
What happens if you have too much myelin?
The signal will decay overtime
What affects conduction velocity?
Thickness, Temperature, myelination
What are electrical synapses?
Direct electrical coupling between the cytosol of two neurons -there is a jap junction between the two neurons
What are gap junctions?
Part of electrical synapse process
- Membranes must come 3.5nm apart
- Made of 6 connexin subunits joining
- It is bidirectional
What are the three types of axon neurons with regards to chemical synapses?
Axo dendritic
- Axo-somatic
- Axo-axonic
Are electrical synapses bidirectional?
Yes they are and they are also faster than chemical synapses
What is an axo dendritic synapse?
Most common type of synapse where the axon terminal is meeting the dendrite
What is an axo somatic synapse?
Where the axon attaches onto the soma (body)
- This is inhibitory
What is an axo-axonic synpase?
Axon attaches onto axon which is attached to axon
- can modulate signal before transmission
What is grays type I synapse?
Based on molecular structure
- Assymetrical
- Round vesicles
- Electron dense
- EXCITATORY
- contact dendritic spines e.g neurotransmitter glutamate
What is grays type II synapses?
Based on molecular strucutre;
- Symmetrical
- Oval vesicles
- Less electron dense
- INHIBITORY
- contact dendritic shaft/cell body e.g. GABA
If there is a 1:1 connection with one terminal will it be stronger or weaker than a 1:1 connection with two presynpatic terminals on the post syn?
It will be weaker as the more synapses there are, the stronger the signalling will be
What are the 4 criteria for neurotransmitters?
- Synthesised in presynaptic neuron
- Defined action on the post synaptic neuron/effector after release from presynaptic neuron
- Exogenous (outside-artificially applying it) administration mimics actions of endogenous (natural) transmitter
- Specific mechanism exists for removing substance from synaptic cleft
What are the three types of neurotransmitters?
Amino acids (Glutamate, GABA, Glycine)
Amines ( Dopamine, Acetylcholine, histamine)
Peptides e.g. dynorphin
How are 2/3 neutrotransmitters ( glutamate and glycine) synthesised?
ALREADY SYNTHESISED IN CELLS - just need to be packaged in terminal
How is GABA (1/3 of aas) and amines synthesised?
They need ENZYMES for synthesis and are TRANSPORTED actively in larger packages by kinesin molecule
Where does neurotransmitter load into vesicles for glutamate?
In the axon terminal
What is a metabotrophic receptor?
Requires a signal cascade associated with a G protein
- This is SLOWER and longer acting
- Has broader, more distributed effects
What is a ionitropic receptor?
Ligand gated
- Fastest receptor but is brief
- Less selective
What is a Post synaptic potetial?
Transient change in membrane poteniral due to neurotransmitter mediated channel opening
(EPSP- Na+ channels opening)
Why is there no y axis on EPSP or IPSP graph?
Because membrane potential depends on number of vesicles released
What does the amount of neurotransmitter released dictate?
How many channels are opened
What are three ways to turn the signal off??
- Diffusion away from synapse (but is not controlled and wasteful)
- Reuptake- neurotransmitter re enters the pre synaptic neuron terminal
- Enzymatic destruciton (e.g. acetylcholinerASE breaks down Ach)
How do we get Ca2+ out of the axon terminal?
Na+/ Ca2+ exchanger (NCX)
- 3 Na + in cell versus 1 Ca 2+ out of cell
What affects the decay of signals?
- Internal resistance (internal diameter)
2. Membrane resistance (which is affected by density of open channels- so the leakiness)
In what situation will charge propagate most easily?
When there is a larger diameter and fewer leaky (K2P) channels open
Do signals propagate bidirectionally in dendrites?
YES!
Synapses clsoer to the soma….
..have a greater influence on the spiking probability (for PSPs of the same size)
Synapses further from the soma…
…have more neurotransmitter receptors (so larger PSP)
Do dendrites always have passive conduction?
NO!! Apparently not..
- Depends on voltage gated channels which boost membrane depolarisations
- It just improves the probability that an EPSP actually leads to the soma
- Don’t cause a large depolarisation and aren’t as reliable
Do dendrites need a lot of inputs to generate an AP?
YES!! Because they are leaky (K2P) channels
What happens if there is a short time constant?
Charge leaks across the membrane very slowly
- Depolarisation stimulus is for longer (so more likely for AP to be generated in downstream neuron)
What happens if there is a short time constant?
Charge leaks across the membrane very QUICKLY and is less conserved (so LESS likely to generate AP)
As you get further from the soma, what happens to the amplitude of the EPSP?
It INCREASES e.g.synapses releasing neurotransmitter on the distals parts of dendrites lead to VERY LARGE EPSPs
What occurs at the ‘trigger zone’?
Siking threshold (minimum potential that an AP will occur at - Trigger zone has a high density of Nav channels
Can EPSPs and IPSPs sum?
YES!!
What is shunting inhibition?
Inhibiting current flow from soma to axon hillock
- If excitatory synapse comes in on dendrite you can ‘shunt’ the charge out closer to the cell body via the chloride ion channels (so there is no net change in mempot)
What is vesicle release probability ?
Probability that vesicles will be released after AP arrives at axon terminal
- Varies between areas
- For example, motor neurons P(release)= 1 (NMJ)
and also cerebellar pyramidal cells 0.1-0.9
What do axo axonal synapses do?
They can regulate Ca2+ entry into the axon terminal
What is paired pulse facilitation?
Two electrical stimuli separated by 100ms lead onto tow distinct waves of Ca2+ influx
In paired pulse facilitation, what is the arrival of the second stimulus associated with?
- Higher intracellular calcium in the presynaptic axon terminal
- Greater neurotransmitter release for second stimulus (so larger EPSP)
What happens if the P release is low?
Paired pulse faciliatation occurs
What happens if Pr is high?
few vesicles ready for release in response to second spike so we get a depression (second change in mempot is smaller)
What is the third way you can modify Pr?
There are autoreceptors (neurotransmitter) that are on the PRESYNAPTIC MEMBRANE (they monitor levels of neurotransmitter in synpatic cleft)
- can also change the rate of neurotransmitter uptake into presynaptic neuron
Is an EPSP closer or further from the cell body larger?
Usually EPSP of more distal synapse will be larger
- but effects at the soma are weaker
What are synpases onto dendritic spines (excitatory or inhibitory)?
Excitatory
What are synapses directly onto the dendritic shaft or dendrite of cell body?
Inhibitory (open Cl- channels)
What are axoaxonic synapses?
Excitatory or inhibitory- modullatory synpase
- controls the probability of neurotransmitter being released by changing how easy it is for Ca2+ channels to open
What is the EPSP size measured close to the synapse affected by?
- amount of presynaptic neurotransmitter released
- amount of presynaptic Ca2+ influx
- no. of post synaptic receptros
- Rate of neurotransmitter re-uptake
What is the size of the EPSP when measured at the CELL BODY affected by?
Membrane space constant
Time constant
Whether active conduction occurs in dendrite (if there are voltage gated channels in dendrite)
