Neurotransmission - Lecture notes Week 3 PDF

Preview

Summary

How do Neurons Transfer InformationResting potentialAction PotentialMyelinationThe synapseNeurotransmittersProperties of the neuron that are important for within neuron communicationWhat causes there to be a membrane potential - the movement of particles across a membrane due to 2 forcesThe equilibr...

Description

The equilibrium potential

The resting membrane potential

What causes there to be a membrane potential - the movement of particles across a membrane due to 2 forces

Conductance

Positive potentials

Action potential

Hyperpolarisation and Demoralisation The Nernest equation

Properties of the neuron that are important for within neuron communication

Voltage gated channels

The action potential

Voltage clamp experiments

Sodium-Potassium pump

Gaba A receptor neural integration: boosting ESPS GABA glutamate

Neural integration interaction of Controlling excitatory and neuronal inhibitory inputs communication

ers

class of neurotransmitters

amplification

metabotrophic receptor

myelin sheath

neurotransmitter action overview neurotransmitter release

neurotransmitter deactivation

How do Neurons Transfer Information

Overview of processes at the chemical synapses

Autoreceptors

ionotropic receptors

post synaptic action of the neurotransmitter

Unmyelinated propagation of the action potential along the axon

Types of synapse

Toxins

se

Chemical synapses

Multiple sclerosis Synapse location Importance of synapse location

oligodendrocytes and Schwann cells

Advantages of myelinated axon

myelinated propagation of the action potential along the axon

Cells of the Nervous System

l and peripheral nervous systems - In the CNS, astrocytes, oligodendrocytes and microglia support neurons by creating an environment conducive to neuronal function, providing a myelin sheath, and activating immune responses - In the PNS, Schwann cells provide myelin and assist with neural regeneration

- The central nervous system (CNS) is located in the brain and spinal cord - The peripheral nervous system (PNS) is outside the brain and spinal cord - The PNS communicates with the CNS via nerves that relay sensory and motor information between the brain and spinal cord and the rest of the body

al

- Neurons include four basic structures: —> the soma: contains the nucleus and many of the organelles —> dendrites: branched structures attached to the soma that receive messages from other neurons —> axon: long thin extension of the soma that conveys electrical message to the terminal buttons —> terminal buttons: extensions of the axon that receive an electrical message and convert it to a chemical message by releasing neurotransmitters into the synapse - Other important structures include: —> cell membrane —> cytoskeleton Provide shape and support for the cell as well as serving additional functions —> cytoplasm —> internal organelles: help the cell survive and include the nucleus, endoplasmic reticulum, Golgi apparatus and mitochondria.

: - The blood brain barrier protects the CNS, selectively permitting only some substances to enter - The barrier is made of capillary walls and helps regulate the composition of fluids in the brain, protecting neuronal transmission - The blood-brain barrier is more permeable in the area postrema, permitting the neurons in the region to detect the presence of toxic substances in the blood.

Communication within a Neuron - A simple withdrawal reflex is made up of a sensory neuron that detects the stimulus, a spinal interneuron that excites a neuron, and a motor neuron that causes the withdrawal behaviour - This reflex can be inhibited by input from the brain that can prevent that withdrawal behaviour by inhibiting the motor neuron

- Resting potential in most neurons is ~ -70mV, or 70 units (mV) more negative inside the neuron compared to outside it - Hyperpolarisation occurs when the inside of the neuron becomes more negative (eg. -100mV) - Depolarisation occurs when the inside of the cell becomes more positive (eg. +20mV) - An action potential occurs when a neuron is depolarised beyond its threshold of excitation - An action potential is a burst of depolarisation followed by hyperpolarisation that proceeds like a wave along the axon, starting at the point where the axon meets the soma and proceeding to the terminal buttons.

- The difference in charge between the inside and the outside of the axonal membrane is generated by the force of diffusion, electrostatic pressure and the activity of sodium-potassium pumps - The force of diffusion describes the process by which molecules distribute themselves evenly throughout the medium they are dissolved in - Electrostatic pressure describes the phenomenon in which like charges repel and opposite charges are attracted to each other - The sodium-potassium pump helps maintain the resting membrane potential by pumping three sodium ions out and two potassium ions into the cell with each molecule of ATP (adenosine triphosphate)

s d - After reaching the threshold of excitation, the voltage-gated sodium channels open, allowing sodium to enter the cell - Sodium’s movement into the cell is driven by forces of diffusion and electrostatic pressure - this depolarises the axonal membrane - After approximately 1msec, the sodium channels become refractory - The positive charge inside the cell opens voltage-gated potassium channels - Potassium exits the cell due to the force of diffusion and electrostatic pressure due to the now positive charge on the inside of the cell - As potassium exits and diffuses away from the cell, the cell becomes hyperpolarised and eventually becomes even more negatively charged inside the cell than resting potential - The potassium channels close, halting exit of potassium ions out of the cell - The sodium-potassium pumps become active, moving three sodium ions out of the cell and two potassium ions in

- After initiating at the point where the axon joins the soma, the action potential propagates towards the terminal buttons according to the all-or-none law - The all-or-none law states that an action potential either occurs or does not occur, and (once triggered) it is transmitted down the axon to its end - In an unmyelinated axon, the action potential proceeds along the axon, but it is subject to decremental conduction - In a myelinated axon, the action potential is conducted via salutatory conduction, which speeds the message, reduces decremental conduction, and renews the action potential at the nodes of Ranvier - To vary the strength of the message conveyed by the action potential, the rate law explains that although each action potential ever to is identical, a stronger message can be conveyed by firing action potentials at a higher rate

n Dendrites: Dendron = tree; recipient of information from other neurons; large receptive field Soma: cell body; contains the machinery that controls processing in the cell and integrates information; contains the nucleus which houses genetic material Axon: carries information (action potential) from the soma to the terminal boutons and hence to other cells; axons can branch to contact multiple neurons Terminal buttons/boutons: found at the end of the axon; location of the synapse; communication point with other neuron

Neuronal Membrane - Boundary of soma, dendrites, axon and terminal buttons - Separates the extracellular and intracellular environment from the intracellular environment - Membrane = lipid belayer (5nm - very thin) - It keeps certain substances so specific information can reach the neuron - Most chemicals in our body are hydrophilic (loves water) which stops most of the substances coming through - Hydrophobic (doesn’t like water) and hydrophilic molecules create a nice membrane that separates things very well - Ion channels in the membrane allow ions to come in - Receptors can receive signals from neurotransmitters which are released and they can detect substances outside the cell (gated: chemical or electrical)` - Cytoskeletal proteins give structure to the cell

Properties of the neurons that are important for within neuron

- Membrane Potential: electrical charge across the membrane —> at rest: difference between the inside and the outside of the neurons is approximately 65-70mV (millivolts) —> at rest: inside is more negatively charged than the outside, inside of the membrane is -65 to -70mV

Resting Potential What causes there to be a membrane potential? - The movement of particles across a membrane due to 2 forces: 1) Force of diffusion: molecules move from an area of high concentration to an area of low concentration - Salt (NaCl) splits into two particles: Na+ and Cl2) Forces of electrostatic pressure: particles with a similar charge repel, while particles with an opposite charge attract - Cations (Na+) => positive ions (pink) - Anions (Cl-) => negative ions (green)

n - Cell with a plasma lipid/bi layer membrane inside a neuron - Lots of sodium outside (positive) - Lots of potassium inside (positive) - A little bit more chloride in outside but not really important - Large organic anions (very negative) stay in the cell and influence the cell to become more negative (acetate and pyruvate) - Resting membrane potential results from this difference in charge across the membrane

1) Positive ions move across the membrane by diffusion force (high concentration to low concentration) 2) As positive ions move there is an increase in electrical potential across the membrane (more positive on one side, more negative on the other size) 3) Eventually a point is reached when diffusion = electrostatic force —> equilibrium potential Equilibrium potential: outward movement = inward movement - Initial concentration difference is important, because high concentration will produce large equilibrium potential and vice versa - Very few ions need to move to achieve this.

- In an axon, you have resting leak channels, that are like a hole in a pipe, they will always be open and allow things to leak out - There are more potassium channels than sodium channels so the opportunity for potassium to leak out of the cellis much bigger compared to sodium leaking into the cell - Each ionic species wants to be the boss and achieve their equilibrium potential - More potassium channels so it will dominate and attempt to reach its equilibrium potential - But a little bit of sodium will leak in and raise the equilibrium potential slightly so it is more positive than potassium’s resting potential

n - The equilibrium can be calculated for any ion (eg Na+ or K+) using the Nernst equation - At body temperature (37.C), can be influenced by temperature (it will change how ionic species move) - 61 is a constant (includes factors like temperature and other constants) - This equation allows you to make predictions and operationalise things such as equilibrium potential - The bigger the concentration difference, the bigger the equilibrium potential (bigger for potassium than sodium because of this)

S

p

- Sodium-potassium pump maintains the ionic concentration gradients (Na+ and K+) across the membrane and therefore resting membrane potential - Uses energy inside cell - This is why we have a high sodium concentration outside all the time in a normal cell and a high concentration of potassium inside the cell the pump is forcing it - Takes energy molecule (ATP) and breaks it down, which releases energy that forces the ions to move against their concentration gradient - Takes sodium from inside to outside and takes potassium from outside to inside the cell, which makes sure there is a high concentration gradient for both ions

- A nerve impulse - Allows communication within the neuron, along the axon - Generated at the axon hillock - Generated either by the summation of converging inputs from the dendrites or by electrical stimulation (experimentally)

Action Potential

Resting membrane potential is around -65 to -70mV

C - Small depolarisation to a neuron - Following a small stimulation there is a small degree of depolarisation that decays along the length of the neuron (decremental conductance) - The closer you are to the injection site, the bigger these depolarisations are, if you are injecting a positive current.

If you inject a negative current, the membrane potential is going to be more negative than the resting membrane potential - this process is called hyperpolarisation - you can also get hyperpolarisation if positive ions move out of the cell (potassium) or negative ions move in (chloride)

If you inject a positive current, the membrane potential will become more positive than the resting membrane potential, so it goes towards zero - depolarisation - you can also get this if more positive ions move in (sodium)

- Increase the size of the stimulation and therefore the degree of depolarisation - Once a threshold of depolarisation has been reached, an ACTION POTENTIAL is fired - This is all or non response (once the threshold is crossed, there’s the point of no return)

- Channels are voltage-gated: opened when the membrane becomes depolarised (controlled by the voltage) - Different to leak/rest channels, as they are always open even at rest, and are like leaky holes in a pipe - Different degrees of depolarisation open the channels - Look at properties using voltage clamp experiments - Positive membrane potentials (very high degrees of depolarisation) results in an inactivation of the Na+ channels

V

s

- At rest, the voltage-gated sodium channels are closed (not doing anything) - Then if there is enough depolarisation, they open a little bit and sodium comes in, the inside of the cell becomes more positive - If there are more positive ions coming in (and so more depolarisation), eventually i reaches the refractory state - at this stage, more depolarisation doesn’t change anything , it is not letting sodium ions pass through anymore (they can’t go in) - The voltage gated sodium ions behave this way because of activation and inactivation gates (biophysical property o these channels) - Diagram on the right shows this process

V

s

- Use an amplifier to artificially inject current into an axon and create a membrane potential to your liking - You can you can artificially stimulate a condition with high degrees of the polarisation or low degrees - If you were to make a neuron a bit more polarised than rest, this means the current is flowing inside first and then a little outside - If you depolarise the neuron a lot towards zero, you still get a current going inside then outside - Eventually the inward curve drops and you only get the outward current - This is what neurophysiologists and electrophysiologists do to study how a current moves under artificial conditions - to better examine what drives the opening and closing of the voltage-gated ion channels and the action potentials

V

- Researcher artificially made it depolarised and looked at the ion conductance (how fast an ion travels through a channel) - When a neuron becomes depolarised, you get an inward current at the beginning and it’s followed by a slow outward current - this is because, what initially happens is that there is a lot of sodium ions going in to the cell really fast through the voltage gated sodium channels, and the outward current occurs because potassium is slowly coming out of the neuron through these voltage gated potassium channels

s

- Closed at rest, but also closed with a little depolarisation - They finally open up when there is lots of depolarisation (almost at zero) - It takes more depolarisation to open up voltage gated potassium channels compared to the sodium channels - Important to the learn the differences in the behaviour of the ion channels to better understand the process of action potential - At a very high depolarisation, the gates are still open (during sodium’s refractory state) - No inactivation gate like with sodium, but they will eventually close at a certain membrane potential

Action Potential - step by step breakdown

1) At resting membrane potential, the majority of the channels are closed

2) Small depolarisation opens a few sodium channels. Sodium begins to move into the neuron (diffusion and electrostatic forces) leading to further depolarisation

3) If the stimulation is large enough (above the action potential threshold) the majority of the sodium channels open and more sodium moves into the neuron (diffusion and electrostatic forces) again leading to further depolarisation

4) As the neuron continues to depolarise, some potassium channels are opened, allowing potassium to leave the neuron (diffusion). The potassium effluent will slow down the rate of depolarisation but at this point more sodium channels are open and sodium is the boss (it wants to sit at the equilibrium potential of +62mV)

5) At positive potentials, the sodium channels become deactivated (refractory) so that no sodium can pass through. the remaining potassium channels open and potassium continues to leave the neuron driven by both diffusion and electrostatic forces (as inside the neuron is now positive). When sodium becomes refractory, potassium becomes the boss and wants to sit at -90mV

6) Potassium continues to leave the neuron (diffusion). The membrane to entail decreases and becomes negative. This is known as repolarisation.

7) The potassium channels begin to close and the sodium channels return to their closed normal state. The membrane potential drops to below the resting membrane potential due to a few remaining open potassium channels and the high concentration of potassium channels outside the neuron. This is known as hyperpolarisation. During this time, another action potential is difficult to elicit.

8) The final potassium channels close and external potassium is diffused away. The membrane potential returns to the resting membrane potential. Sodium and potassium pumps work like mad to restore resting membrane potential

: unmyelinated - The action potential is the same size at each point along the axon: all-or-none response (no matter where you measure on the axon, you will get the same action potential - Propagation of the action potential along the axon is unidirectional

In an unmyelinated axon, if an action potential is propagating, you get a depolarisation and a peak of action potential but it is already spreading to the adjacent area, and then the other area - looks like a rope that has been whipped - and the impulse is spreading.

*** electrical impulses gather in the axon hillock to generate an action potential

Myelination : fatty tube placed around the axon by either an oligodendrocyte or a Schwann cell

Propagation of the action potential along the axon asymmetrical, forms myelin around axons in brain and spinal cord

- Unmyelinated vs myelinated axons

s: asymmetrical, wraps around peripheral nerves to form myelin

- The generation if an action potential requires energy (sodium-potassium activation) and time - Less action potentials are needed to send a nerve impulse along a myelinated neuron than an unmyelinated neuron - The action potentials jump and impulses are quicker, it doesn’t have to occur in many places - Communication can become more synchronous, your movements become fast so it is important for coordination - Some neurons in the brain do not have myelin but they serve different purposes (eg pain transmission, which needs to be slower to be effective)

- Action potentials can only occur at the nodes of Ranvier as this is the only place where potassium and sodium can pass through the channels - This is because depolarisation decays along the length of the myelinated sections - The depolarisation is built up at the nodes of Ranv...