Electophysilology I: Spikes, Graded Potentials & Synaptic Integration

Question 1

What is used to evaluate the electrical activity in the brain?

Answer 1

Electroencephalogram (EEG) - electrodes (5-10mm in diameter) attached to the scalp with standardised placement

Question 2

What is an Electroencephalogram (EEG)?

Answer 2

An amplified recording of the waves of electrical activity that sweep across the brain’s surface. These waves are measured by electrodes placed on the scalp.

Question 3

What are the Frequency elements of EEG?

Answer 3

The EEG pattern contains frequency elements, which are categorised into four states:

Delta: 0.5-4Hz
-deep sleep

Theta: 4-8Hz
-drowsiness

Alpha: 8-14Hz
-relaxed, alert

Beta: 14-30Hz
-highly alert

Question 4

What is an evoked potential?

Answer 4

An evoked potential (event-related potentials) is an average EEG waveform with respect to stimulus onset

Question 5

What is required to resolve evoked potentials?

Answer 5

Because evoked potential amplitudes tend to be low, signal averaging is usually required to resolve these low-amplitude potentials against any background ‘noise’

Question 6

What is signal averaging?

Answer 6

signalling process technique used to increase the strength of a desire signal relative to the unwanted background ‘noise’ that is obscuring it

noise is the unwanted sound that would usually overpower the signal if you took just one measurement
-by taking an average, the signal-to-noise ratio (SNR) will be increased

Question 7

How does signal averaging work?

Answer 7

obtained by ‘time-locking’ the EEG recording with a presentation of a stimulus (e.g. auditory click)

assumption is that the signal, triggered by a stimulus, will stay relatively constant over multiple trials, and all the other signals would occur randomly across trials

so, when averaging several trials, the desired signal will stand out whereas the noise will average to zero

Question 8

What does a signal-to-noise ratio compare?

Answer 8

compares level of a desired signal to level of background noise

Question 9

What is the challenge of EEG technology?

Answer 9

electrical activity generated by the brain is miniscule, so scalp-recorded electrical activity consists of brain signals combined with noise generated by other parts of the body (e.g. heart activity, facial muscle movements and eye movements)

Question 10

What are the major sources of noise in EEG signals?

Answer 10

There are two major sources of noise in EEG signals:

• general background noise that comes from outside the brain
• natural brain noise which originates inside our brains as our brains are doing many things at once

Question 11

How is the geometry of cortical neurones within the cortex advantageous for EEG imaging?

Answer 11

Cortical neurones are perpendicular to the surface, meaning that signals flowing due to synaptic activity and action potentials will be oriented in the extracellular space, and therefore signals have the opportunity to ‘sum up’ across neighbouring neurones.

This geometry allows for the possibility that the local current generated in the extracellular medium by neuronal signalling can sum and get conducted and ultimately picked up and amplified by EEG.
-if they were all at different random orientations, the extracellular current would tend to cancel ou

Question 12

What is an electrocorticogram?

Answer 12

Electrocorticography (ECoG), or intracranial electroencephalography (iEEG), is a type of electrophysiological monitoring that uses electrodes placed directly on the exposed surface of the brain to record electrical activity from the cerebral cortex

Question 13

What is the Local Field Potential (LFP)?

Answer 13

electrical field generated by the summed, synchronised activity of a large number of neurones, typically recorded by using micro-electrodes (metal, silicon or glass micropipettes) inserted through grey matter

Question 14

What is the difference between LFP and EEG?

Answer 14

LFP recordings are invasive, and they sample relatively localised populations of neurones, whereas EEG samples larger populations of neurones

Question 15

What is the highest level of electrical resolution in the brain?

Answer 15

Intracellular recording from single cells
-records potential difference across membrane (membrane potential)

fine glass pipettes with a very fine tip are inserted into the cortical grey matter and the idea is that the intracellular electrode will actually pierce the cell membrane and the electrode tip will record the voltage difference between the inside of the cell and a reference electrode which will be in the extracellular fluid

Question 16

What is the difference between extracellular and intracellular recording from single cells?

Answer 16

Extracellular:

• Cannot record voltage difference across membrane (membrane potential, Vm)
• Spikes in nearby neurones cause local extracellular current flow, which can be detected as transient voltage change

Intracellular:

• Electrode tip is actually inserted through the membrane and so record voltage difference across cell membrane (Vm)
• concept of having second electrode to inject current

Question 17

How is the intracellular membrane potential recorded?

Answer 17

Microelectrode inserted through the cell membrane so that the electrode tip is inside the cell. Reference electrode will be in the extracellular medium. The amplifier is measuring the voltage difference that is picked up by the electrode inside the cell and the electrode outside the cell. Whatever the voltage is outside will just be set to 0 arbitrarily.

While the electrode is still in the extracellular medium it would read 0mV, then when it penetrates the membrane you get a drop-in voltage to whatever the resting potential (~-70mV).

If you keep on increasing the depolarising stimulus, at some point the neurone will fire an action potential. At this point, we have departed from the passive graded potentials and achieve action potentials. This is not graded because it is all-or-nothing. The frequency of action potentials also increases with increasing stimulation (not amplitude).

Question 18

What are graded potentials?

Answer 18

temporary localised changes in membrane potential, the characteristics of which depend on the size of the stimulus

Question 19

Give some Examples of graded potentials.

Answer 19

In an experiment
-subthreshold changes in Vm due to intracellular current injection

Physiologically
-EPSPs and IPSPs, which are small voltage changes generated at synapses

In sensory neurones
-receptor potentials from sensory transduction

Question 20

What is the difference between graded potential and action potential?

Answer 20

Graded potentials are brought about by external stimuli (in sensory neurones) or by neurotransmitters released in synapses, where they cause graded potentials in the post-synaptic cell.

-amplitude is proportional to the strength of the stimulus, which can either be depolarising or hyperpolarising

Action potentials are triggered by membrane depolarisation to threshold

• amplitude is all-or-nothing
• strength of the stimulus is coded in the frequency of all-or-nothing action potentials generated
• therefore, with increasing stimulus, frequency of APs increases but amplitude stays the same

Question 21

What are neuronal outputs?

Answer 21

Neuronal outputs are action potentials (spikes) that are actively propagated down the axon

They reach synaptic terminals and evoke synaptic transmission onto target neurones

Question 22

Where are neuronal outputs typically generated?

Answer 22

soma

-then actively propagated along the axon

Question 23

What are neuronal inputs?

Answer 23

Neuronal inputs are synaptic potentials (graded potentials) which determine whether a neurone generates an action potential or not

• Physiologically, the inputs to neurones would be via EPSPs and IPSPs which are generated at dendritic spines in response to spikes in presynaptic neurones. They are passively propagated from dendrites to soma
• In an artificial experiment, the input could be a graded potential that we depolarise up to threshold to generate an AP

Question 24

What are EPSPS?

Answer 24

Excitatory Post-synaptic Potentials

• caused by the influx of Na+ or Ca2+
• increases likelihood of postsynaptic cell to fire an action potential

Question 25

What are IPSPs?

Answer 25

Inhibitory Post-synaptic Potentials

• caused by the influx of Cl- or efflux of K+
• makes the cell less likely to have an action potential

Question 26

Explain the Process of Synaptic Transmission.

Answer 26

Action potential in pre-synaptic neurone triggers a post-synaptic potential in a post-synaptic neurone.

• neurotransmitter secreted from pre-synaptic binds to receptor on post-synaptic membrane, opening ion channels and allowing local current flow
• results in local change in Vm, which may be de- or hyperpolarising
• changes in Vm due to single PSPs are usually small (in the mV range)
• PSPs are graded potentials: they can summate and produce voltage changes large enough to bring the membrane to threshold for action potential generation (or not)

Question 27

What is spatial summation?

Answer 27

many pre-synaptic neurones with synapses on different spatial locations on the post-synaptic neurone are activated simultaneously, in which case the individual PSPs can summate to determine the membrane potential of the post-synaptic cell

Question 28

What is temporal summation?

Answer 28

summing several graded potentials from one pre-synaptic neurone

• time course of an action potential is slower than PSP
• if spikes occur in sequence, the PSP from the first spike will not have decayed by the time the second PSP is generated, therefore it summates until enough to reach threshold

Question 29

What is the difference between action potentials and synaptic potentials?

Answer 29

Action potentials (spikes):

• Large (~100mV)
• Faster (c. 1ms)
• All-or-nothing
• Cannot summate (don’t interact with each other)
• Active
• Voltage change

Synaptic potentials (graded potentials):

• Smaller (≤1mV)
• Slower (c. 10ms)
• Graded
• Can summate
• Passive
• Chemical

Question 30

What is synaptic integration?

Answer 30

Over any given (brief) time window spatial and temporal summation determine the value of Vm.

If the sum of all inputs (EPSPs and IPSPs) that have occurred in that time add up to a value of Vm that is more positive than threshold, an action potential is generated, otherwise not

Question 31

What determines summation?

Answer 31

electrical properties of the neuronal membrane

Question 32

What are the electrical properties of the neuronal membrane which determine summation?

Answer 32

Space Constant (Length Constant) ƛ

• increases with diameter
• increases with membrane resistance

*space constant is the length along the membrane that it takes the voltage to decline 37% of its initial value

Time Constant, t
-t= RC

• R is the membrane resistance, and C (constant) is the membrane capacitance
• time constant is the amount of time it takes the voltage to fall to some specified level from the initial level

Question 33

Long length/space constant means…

Answer 33

a potential generated at one point along the membrane will decline less with distance than if there is a short length constant
-voltage decay with distance will be less than if it is a small number

Question 34

Long time constant means…

Answer 34

the voltage will fall slowly

Question 35

Short time constant means…

Answer 35

the voltage will fall rapidly

Question 36

How can we change the time constant?

Answer 36

t= RC

Because C (membrane capacitance) is a constant, to change the time constant we depend on R (membrane resistance)

We can change the number of open channels, which will decrease the membrane resistance

• this gives a faster time constant and therefore a faster neurone
• however, this is more metabolically expensive because more open channels are required and active transport is needed to maintain the concentration gradient

Question 37

How are space/length and time constant linked to summation?

Answer 37

Space constant is conceptually linked to spatial summation.

• With a long space constant, two neurones activated simultaneously can summate enough to trigger to a spike over threshold and generate an action potential
• With a short space constant, they both decay a lot and despite the summation, they are still not going over threshold

Time constant is conceptually linked to temporal summation

• With a long time constant, the EPSP will slowly decay and the second EPSP comes a short time later and summates, triggering an action potential
• With a short time constant, the EPSP decays rapidly and by the time the second EPSP comes it has decayed to baselines and so we don’t have summation