Nerves Flashcards
What are the subdivisions of the nervous system
- CNS: Brain, Spinal cord
- PNS: Autonomic (symoathetic/parasympathetic/enteric), Somatic
See diagram
Lable parts of brain (name them)
See sheet for diagram
- Meninges
- Gyrus vs. sulcus
- Cerebellum
- Cerebrum- frontal lobe, temporal lobe, parietal lobe, occipital lobe
- Diencephalon- thalamus, hypothalamus
- Brainstem- midbrain, pons, medulla oblongata
Number of pairs of spinal nerves
31
give the arrangement of spinal nerves
- 8 cervical (although 7 vertebrea)= neck, shoulders and arms
- 12 thoracic= chest and abdomen
- 5 lumbar= hips and legs
- 5 sacral= genitalia and gastrointestinal tract
- 1 coccygeal
Lable the spinal chord cross section
See diagram
Nerve afferent
Sensory info (go in)
Nerve efferent
Motor (go out)
What is grey matter/what makes it grey
cell bodies
Why is white matter white
myelin - white fibres
Anatomy of a neuron
- dendrites- receive information
- cell body (soma)- contains the nucleus
- initial segment (axon hillock)- triggers action potential
- axon- sends action potential
- axon (presynaptic) terminals- releases neurotransmitter
see picture
Types of neuron
Afferent (sensory) neurons PNS —> Interneurons CNS —> efferent (motor) neurons PNS
Moorphology of neurons
- afferent (sensory) neurons= bipolar, pseudounipolar
- interneurons= multipolar, anaxonic
- efferent (motor) neurons= multipolar
what are glia
Cells that support neurons (non-neuronal cellsof the brain/nervous system)
Types of glia cells in CNS
astrocytes, oligodendrocytes, microglia, ependymal cells
What do astrocytes do
- Maintain external environment for the neurons
- Surround blood vessels and form blood brain barrier
What do oligodendrocytes do
Form myelin sheaths in the CNS
what do microglia do?
macrophages of the CNS, hoover up infection
What do ependymal cells do?
produce the cerebrospinal fluid
Tyopes of glial cells in PNS
Schwann cells and satellite cells
What do Schwann cells do?
form myelin sheath in PNS
What do satellite cells do?
support neuron cell bodies
What does a neuron look like?
see picture
How do neurons send electrical signal
Action potentials= transmit signals over long distances
Graded potentials= decide when an action potential should be fired
Resting membrane potentials= keeps cell ready to respond
What is the resting membrane potential
- Inside potential of cell relative to outside
- Outside taken as 0mV and inside relative to this (usually -70mV in neurons)
- Aka potential difference
- Inside is negative
How do we create a resting membrane potential
- Phospholipid bilayer impermeable to water and ions
- Assume equal concentrations of NaCl and KCl inside and outside the cell
- Everything is balanced inside and outside the cell - No membrane potential
Then…
- Na/K pump uses ATP to pump K into and Na out of the cell
- charges still balanced (ish) - still no membrane potential
Then…
- Add “leaky K” channel
- Some K leaks out cell down its conc gradient
- Builds up electrical gradient
- Equilibrium is reached when electrical gradient is equal and opposite to conc gradient
- Have resting membrane potential
Explain the movement of K+ in terms of conc and electrical gradient
- Conc gradient - K+ beign pulled out
- Electrical grad - K+ being pulled in
How is resting membrane potential determined
By size of initial conc gradient:
* Small conc grad = small resting membrane potential
* Large resting membrane potential = need lots of K+ to leak out to reach equilibrium
What is the equilibrium potential
The equilibrium potential is the membrane potential at which the electrical gradient is exactly equal and opposite to the concentration gradient
Nernst equation
equation predicts the equilibrium potential for a single ion species
see picture
What is the nernst equation usually at 37 degrees
for K+, approx -90 mV, for most neurons it is closer to -70 mV due to other “leaky” channels, especially Na+ and Cl-
What does the Goldman-Hodgkin-Katz (GHK) equation do
Predict the equilibrium potential generated by several ions
see picture
why is the Na/K+ ATPase not completely responsible for generating the resting membrane potential?
- Exchanges 3 Na+ for 2 K+ meaning it is Electrogenic (makes the inside of the cell slightly negative)
- Only contributes about 5 mV Na+/K+ pump is needed to set up the ion gradients
- Without leaky K+ channels, only a small membrane potential would be generated
What is resting membrane potential dominated by
The permeability of the resting membrane to K+
briefly summarise leaky K+ channels
K+ continually leaks out the cell down its conc gradient (against electric grad), which was established by Na/K pumps. Why resting membrane potential close to K+ equilibrium potential - only close due to other leaky channels
Blood-brain barrier
Capillaries in brain which prevent polar substances from crossing through/between endothelial cells. Protects brain from changes in plasma ion conc
What does the resting membrane potential produce
Evoked potentials (graded or action)
2 types of potential
- graded
- action
Graded potential
any change in electric potential of a neuron that is not propagated along the cell (as is an action potential) but declines with distance from the source
What do graded potentials decide?
Jotted down, might not be “true”
Whether a cell is depolarised past a threshold to fire an action potential - decide when action potential is fired
examples of graded potentials
- Generator potentials- at sensory receptors
- Postsynaptic potentials- at synapses
- End plate potentials- at neuromuscular junction
- Pacemaker potentials- in pacemaker tissues (heart)
How do graded potentials respond to small and large stimuli
- Small stimulus opens a few channels and evokes a small response (small depolarisation)
- Strong stimulus opens many channels and evokes a large response (large depolarisation)
What does this mean graded potentials can also signal (what other bit of info can they share)
Stimulus intensity in their amplitude
What is a key propety of graded potentials
think how they change
They are decremental
Why are graded potentials decremental?
Become smaller as they travel along the membrane, therefore only useful over very** short distances**, this is why graded potentials are also called local potentials
What 2 things can graded potentials be
Depolarising or hyperpolarising
explain depolarising and hyperpolarising of graded potentials
Neurotransmitters can open channels that depolarise the cell, or different channels that hyperpolarise the cell. Since firing an action potential depends on reaching a firing threshold. Graded potentials at synapses can therefore excite or inhibit a cell
What does depolarising a cells do/mean
graded potentials
Less negative value - Exitory postsynaptic potential (EPSP)
What does hyperpolarising a cell do
graded potentials
Away form threshold (less likely to fire action potiential) - Inhibitory postsynaptic potential (IPSP)
What can multiple graded potentials do together?
Summate
how can graded potentials summate?
- A single neuron has lots of synapses, evoking their own postsynaptic potential - 1 neuron can have hundreds of neurons attached on dendrites
- If two occur at the same time, they can add to together
- This is important for synaptic integration
Ionic bases of graded potentials
summary
- We already know that at rest there are lots of leaky K+ channels - continually allow K+ into cell down conc grad (generates resting membrane potential)
- That explains why the RMP is close to the K+ equilibrium potential of -90 mV
- The opening of other ion channels generates other ion gradients
- We can predict what would happen in each case
What can happen with ion channels in relation to graded potential
Can open/close them to hyperpolarise or depolarise the cell
Ionotripic receptor
ligand gated ion channels (ion channel + receptor) - through which ions pass in response to a neurotransmitter
Metabotropic recepor
metabotropic receptors require G proteins and second messengers to indirectly modulate ionic activity in neurons
what are the properties of graded potentials?
graded, decremental, depolarising or hyperpolarising, can summate
What causes a fast IPSP (hyperpolarising)
ionotropic receptor (Cl- into cell)
What causes a slow IPSP
metabotropic receptor (K+ out)
Non-specific monovalent cation channel
For aqueous pathway for single positively charged ions to flow down their electrochemical gradient into/out of a cell
What causes fast EPSP
ionotropic receptor (for Na/K…)
What causes a slow EPSP
metabotropic receptor (stops movenet of K+ out of cell - closes)
What does the G-protein act as with metabotropic receptors
Doorman: to find and close “leaky” K channels (Na/K pump still going so cell depolarises
How are EPSPs generated?
EPSPs generated by opening (non-specific monovalent) Na+/K+ channels or closing leaky K+ channels
how are IPSPs generated?
IPSPs generated by opening Cl- channels or opening K+ channels
What is EPSP
an excitatory postsynaptic potential, a local depolarization of the cell membrane of the neuron. Summation of EPSPs can lead to the generation of an action potential.
What is an IPSP
inhibitory post synaptic potential,
hyperpolarization of cell membrane of neuron
What is the principle inhibitory neurotransmitter in the CNS?
GABA
Would GABA hyperpolarise or depolarise neurons
As an** inhibitory neurotransmitter**, GABA usually causes hyperpolarization of the postsynaptic neuron to generate an inhibitory postsynaptic potential (IPSP) while
Glutamate - neurotranmitter action
glutamate causes depolarization of the postsynaptic neuron to generate an excitatory postsynaptic potential (EPSP)
What are GABA and glutamate
GABA - princible inhibitory neurotransmitter in CNS
Glutamate - principle exitory neurotransmitter in CNS
Can GABA/Glutamate act on more than one type of recepor (gating an ion channel)
Yes
Is depolarising EPSP or IPSP
EPSP
Is hyperpolarising EPSP or IPSP
IPSP
What does each neuron have hundreds of
exitory and inhibitory synapses
What does each exitory/inhibitory synapse evoke
Fast or slow EPSP’s and fast or slow IPSP but each is only a few mV high
What does adding together all the tiny EPSP/IPSPs do
Either push cell to threshold and fire an action potential or keeps cell away from threshold and tells it to shutup
Synaptic integration definition
The summation of the synaptic inputs to decide in the initial segement will reach threshold and fire action potential
What happens for synapses that are distant from the initial segment (axon hillock) in terms on firing activity/
Have less of an influence on the firing activity of the cell than those that are closer.
When are action potentials used
over long distances
Steps in firing of an action potential
- Depolarisation
- Repolarisation
- Undershool (more -ve) and then hyperpolarise
Give the steps of firing an action potential in more detail
- Leaky K+ channels maintain membrane potential
- Voltage-gated Na+ channels open, leading to a influx of Na+ into the cell
- Rapid depolariseation of cell occurs
- Voltage-gated K+ channels open (letting K+ out) and Na+ ones close, allowing for a slow repolarisation of the cell
- K+ channels open when reach -55mV
- K+ channels close and cell returns to resting membrane potential
+ ball and chain blocking channels where appropriate
How does the ball and chain function in action potentials
Closes voltage-gated Na/K channels, preventing the entry/exit of ions into the cell
What are the 2 periods in the firing of an action potential - describe both
- Absolute refractory period - Is the period of time during which a second action potential ABSOLUTELY cannot be initiated, no matter how large the applied stimulus is
- Relative refractory period - Is the interval immediately following the Absolute Refractory Period during which initiation of a second action potential is INHIBITED, but not impossible.
Properties of action potentials
- Have a threshold
- All-or-none (always same amplitude)
- Self-propagating - keeps going
- Have refractory period - ball/chain inactivation gate
- Travel slowly
What can action potentials only encode
Stimulus intensity in firing frequency, not amplitude
What are all action potentials mediated by
Voltage-gated channels (as opposed to ligand-gated channels that generate postsynaptic potentials)
What will a stronger stimulus show in an action potential
More action potentials fire
Explain the movement of action potentials down the axon
- Cell -ve at rest
- Na+ channels open, allowing influx of Na+ into cells at that point on the membrane—> depolarisation
- Now, neighbouring Na+ channels open, depolarising this part of the membrane
- Initial Na+ channels blocked by ball and chain, close off, stopping influx of Na+ - clamps channels closed and stops signals going the wrong way down the neuron
- Process continues and signal moves all the way along the neuron
What mediates the depolarising, repolarising and hyperopolarising phase
- Depolarising - Voltage-gated Na+ channels
- Repolarising - Voltage-gated K+ channels
- Hyperpolarising - Voltage-gated K+ channels
Benefit but also drawback of action potentials
Self-propagating = grate but slow
How can we spped up conduction velocity of action potentials
2 ways
- Larger diameter axons
- Myelination
Explain how large (diameter) axons increase conduction velocity
- Current flows more easily along large axon where axial resistance is lower
- Allows the Na+ channels to be more spaced out along the membrane
Explain how myelination increases conduction velocity
- Schwann cells in PNS and oligodendrocytes in CNS
- Wrap layers of myelin arounf axons
- Inc membrane resistance - less current leaks out of membrane
- Dec membrane capacitance -less current wasted charging up membrane
- Action potential spreads passively from nod to node and still reach threshold
- Known as saltatory conduction
Essentially, what does myelination do?
Allows action potentials to “jump” from one node to the next
What are some consequences of demyeination
- multiple sclerosis in CNS and Guillain-Barre syndrome in PNS
- both demyelinating diseases that attack the myelin sheath
- Dec membrane resistance and inc membrane capacitance
- ** Conduction fails** - depolarisation fails to spread
How can nerve fibres differ?
nerve fibre types
Axons different:
* small and large unmyelinated and myelinated axons
all conduct at different velocities, genertes a compound action potential
Give nerve fibre types going from fastest to slowest
- Large myelinated (Aa) - proprioception, motor neurons
- Large myelinated (AB) - Touch, pressure
- Small myelinated (Ay) - motor neurons of muscle spindles
- Smallest myelinated (A#) - touch, cold, “fast” pain
- Unmyelinated (C) - warmth, “slow” pain
What do extracellular recording from a nerve (bundle of axons) generate
A compound action potential - looks nothing like an action potential
Compare action potential to compound action potential
Action potential:
* Intracellular recording
* microelectrode through membrane
* relative to outside the cell
Compound action potential:
* extracellular recording
* electrodes outside axons
* relative to earth
* each action potential very small but add up to large waves
thus, differennces in axon anatomy will lead to differences in …
Conduction velocity
What correlates with an axons function
Anatomy and conduction velocity
Nodes of Ranvier
specialized regions in the axonal membrane that are not insulated by myelin
Briefly summarise the neuromuscular junction and why we have it
Synapse between motor neuron and skeletal muscle
First step in triggering muscle contraction is to evoke an action potential in the skeletal muscle membrane (the sarcolemma)
Describe the anatomy of the nmj moving across the junction
- Preynaptic terminal filled with vesicles containing acetylcholine (ACh)
- Synaptic cleft
- Postsynaptic end plate of the skeletal muscle fibre
Fold in end plate - allows greater uptake
What does depolarisation of a motor neuron do
Depolarises skeletal muscle (nmj) —> action potenital being evoked leading to contraction of muscle
Give steps of firing of the nmj
12 steps
- Action potential in motor neuron - mediated by voltage-gated Na channels (depolarises)
- Opens voltage-gated Ca2+ channels in presynaptic terminal - Ca2+ pulled in by conc and elec gradient
- Fusion of vesicles (Ca2+ dependent exocytosis)
- ACh diffuses across synaptic cleft
- ACh binds to ACh (nicotinic) receptors - ionotropic (non-specific cation channels)
- opens ligand-gated Na+/K+ channles —> pull into cell
- Evokes end plate potential (graded potential), very large
- (Always) depolarises membrane to a threshold
- Opens voltage-gated Na+ channels
- Evokes action potential
- Action potential propagated along muscle cell membrane leading to muscle contracts
- Acetylcholine (ACh) cleared up by acetylcholinesterase
Describe acetylcholine (ACh) receptors
Contain integral ion channel - ligand gated (non-specific monovalent cation channel) - muscarinic or nicotinic
What are some key characteristics of the nmj
- Ligand gated Na/K (2 diff channels) channels evoke the end plate potential
- Very large graded potential which is always bid enough to reach threshold
- Thus, no synaptic integration - nmj acts like a switch
- Post-junctional folds inc number of voltage-gated Na+ channels close to where it is evoked
What is the end plate potential (with nmj)
very large
What do post-junctional folds allow for
The end plate potential has a short distance to travel to the voltege-gated Na+ channels
how is the sequence of events similar/different in CNS synapses to that in NMJ
Same, however CNS synapses have added complexities
CNS synapses compared to NMJ in terms of neurotransmitters
NMJ: acetylcholine
CNS: many inc amines (adrenaline/noradrenaline/dopamine, serotonin (5HT), histamine), amino acids (glutamate, GABA, glycine), peptides (endorphins, cholecystokimim. substance P), purines (ATP, adenosine), gases (nitric oxide)
How can postsynaptic potentials be in the CNS
exitory, inhibitory, fast or slow
(e.g. slow IPSP or fast EPSP)
this range allows for complex synaptic integration
How may postsynaptic potentials are there in the NMJ
1
How can CNS synapses be arranged (3)
- Axo-dendritic - typically exitory
- Axo-somatic - typically inhibitory
- Axo-axonal - can be both but usually inhibitory (work by regulating how much neurotransmitter is released)
How is CNS synapse anatomy different to that of NMJ
CNS: 3 arrangements
NMJ: 1
How can are synapses connected in the CNS and how does this differ to the NMJ
- Divergence - influences cells further down
- Convergence
NMJ: Only have divergence (1 motor neuron synaps onto multiple muscle fibres)
Do NMJ have feedback inhibition
No
Explain feedback inhibition in relation to CNS synapses
- When action potential fired, collateral (branch) activates an inhibitory interneuron
- Inhibitory neurotransmitter released
- Initial neuron hyperpolarises
- it is prevented from repeated firing
Net effect: initial neuron inhibited from repeated firing of action potential
Give an overview of the complexity of pathways in the CNS
Monosynaptic reflex: stereotyped: detect stimuli and fire action potential, limited scope for synaptic integration or for the behaviour of motor neuron to be influenced bu convergent pathways (simple)
Polysynaptic reflex: multiple sites of peotential synaptic integration so multiple neurons where behaviour will be influenced by convergent pathways. Much more complex decisions made and less likely to be stereotyped (same every time)
Explain inhibitory reflex pathways in the CNS
Inhibitory interneuron releases inhibitory neurotransmitter (e.g. GABA) and stops efferent (motor) neuron intitiating a response
What is synaptic plasticity
- Ability of synapses to change their strength.
- can be activity-dependent
- Many diff types of synaptic plasticity:
Long-term potentiation (LTP involved in learning and memory)
Long-term depression
Overall, what makes CNS synapses more complicated than the nmj?
- Range of neurotransmitters
- Range of postsynaptic potentials
- Arrangement of synapses
- Arrangement of wiring
Synaptic pathway
hormones are produced in the neuron, secreted, and travel along the axon to the synapse where they are released and taken up by a nearby neuron with the appropriate receptors to exert an effect, enter via afferent (sensory) neuron and leave via afferent (motor) neuron
how do we classify nerve fibre types
divided into three types on the basis of the relationship between their diameter and conduction velocity: group A, group B and group C nerve fibres.
What is a synapse in basic terms
Jucntion between neurons and a way of communicating between neurons
Common exitory neurotransitter
Glutamate
Common inhibitory neurotransitter
GABA
What can we call the process of 1 neuron releasing a neurotransmitter at its synapse which evokes a reponse in the next neuron
signal transduction
Where are interneurons found
The CNS only
function of acetylcholinesterase
to terminate neuronal transmission and signaling between synapses to prevent ACh dispersal and activation of nearby receptors. - breaksdown ACh
Function of graded potential (postsynaptic, generator potential, end-plate potential)
to determine when/weather a cell will fire its action potential
Where does Acetylcholinesterase remove ACh from
Acetylcholinesterase does not directly remove ACh from the receptors. Instead it continuously removes ACh from the synaptic cleft so there is less chance of ACh activating the receptors.
Synaptic integration in the CNS
In the CNS the EPSP evoked at a single synapse is likely to be in the order of 1-5mV. It is therefore not going to let the cell reach threshold. Instead, summation of EPSPs from many synapses is required. This is the concept of synaptic integration.
Also IPSP’s so add/subtract
When does the equilibrium potential for an ion occurs
when the concentration gradient for the ion is matched by an equal and opposite electrical gradient
Multiple sclerosis
demyelinating disease which impairs the ability of the action potential to be conducted from one node of Ranvier to the next
Can action potentials summate?
No (graded postsynaptic potentials can)
What effect would inc extracellular [K+] have on the resting membrane potential
Will decrease the K+ concentration gradient. This will sustain a smaller electrical potential at equilibrium and therefore depolarise the resting membrane potential.
effect of poisining Na/K pumps
The electrogenic nature of the Na+/K+ pump (pumping 3 Na+ ions for every 2 K+ ions) makes only a small contribution (about 5mV) to the resting membrane potential. Setting up the K+ concentration gradient is far more important. Poisoning the pump will therefore only cause a small immediate decrease in membrane potential. The remainder of it decays slowly as the K+ concentration gradient gradually runs down.
What could we say is at the NMJ (in terms or 1 motor neurone innervatign multiple muscle fibres)
Divergence
