Lecture 29. Synaptic transmission and neural integration

Question 1

what signals are predominant in the mammalian brain?

Answer 1

chemical

in infants- can be electrical

Question 2

How is a message transmitted between neurons

Answer 2

the pre-synaptic neuron transmits AP through its axon. At the end of the axon and before the dendrites of the next neuron there is axodendritic synapse. Neurotransmitters are released generating a signal in the next neuron

Also happens neuron to muscle fibre

Question 3

Neuromuscular junction ‘End plate’

Answer 3

the synapse in the muscle fiber

Question 4

Chemical events of signal transmission

Answer 4

1. AP arrives at the presynaptic terminal
2. It opens V-gated Ca2+ channels, allows Ca2+ into the terminal
3. Ca2+ makes the neurotransmitter vesicles merge with the cell membrane-> release the neurotransmitter into the synaptic cleft
4. Neurotransmitter binds to the receptors on the post-synaptic terminal and opens ligand-gated ion channels
5. Cations(Na+ and K+) flow
   6, This Generates potential in the muscle cell- N-plate potential
6. N-plate potential will travel both ways and create AP both ways

Question 5

N-plate potential

Answer 5

the potential( not AP) generated in a muscle fiber (induced by a neuron)

Question 6

What neurotransmitter is used in muscle?

Answer 6

Acetylcholine

The ONLY one in human neuromuscular junction

Question 7

What is special about the neuromuscular transmission in humans?

Answer 7

• End-plate potential is always suprathreshold (always triggers an AP). Once triggered, AP is transmitted along the muscle fibre.

Once the neurotransmitter is released the AP will always be formed in a muscle fibre

Question 8

What diseases affect the generation of AP in muscle fiber?

Answer 8

Myasthenia gravis
Acetylcholine gated channel gets damaged
-> less channels-> End plate potential is not suprathreshold-> AP does not get generated

Question 9

Are there inhibitory synapses in the neuromuscular junction?

Answer 9

no

Question 10

2 main types of chemical synapses in CNS

Answer 10

• Excitatory

- Inhibitory

Question 11

Excitatory synapse

Answer 11

Depolarisation( more +ve) of the postsynaptic membrane called the Excitatory Postsynaptic Potential (EPSP)

Question 12

Inhibitory synapse

Answer 12

Hyperpolarisation ( more -ve) of the postsynaptic membrane called the Inhibitory Postsynaptic Potential (IPSP)

Question 13

What are the main neurotransmitters forming an excitatory post synaptic potential(EPSP)

Answer 13

Glutamic acid( glutamate) or acetylcholine(Ach)

Question 14

What is the mechanism of EPSP?

Answer 14

Transient opening of channels permeable to Na+, K+ and sometimes Ca2+
on the post-synaptic neuron

Question 15

What is the most common inhibitory neurotransmitter( IPSP)?

Answer 15

GABA or glycine

Question 16

What is the mechanism of GABA( IPSP)?

Answer 16

transient opening of K+ channels

K flows out-> more -ve inside the cell-> hypopolirazation

Question 17

2 types of neurotransmitters

Answer 17

Small molecule neurotransmitters ( classical)

Neuropeptide( ‘neuromodulators’)

Question 18

Small molecule neurotransmitters ( classical)

Answer 18

• Usually fast action (~millisecs) and direct on postsynaptic receptors
- Amino acids: glutamate, GABA, glycine
- Acetylcholine (ACh)
- Amines: serotonin (5-HT), noradrenaline,
dopamine

Question 19

Neuropeptide( ‘neuromodulators’)

Answer 19

• Large molecule chemicals that are slow (~ secs to mins) and usually a more diffuse action.( acts on a wider area)
• Have an indirect (‘metabotropic’) action on postsynaptic receptors or modulatory action on the effects of other neurotransmitters
-Do not directly bind to receptors and change the membrane potential. But they either increase the number of neurotransmitters or the number of receptors

• Several dozens of neuropeptides have been identified which may be involved in
  communication between neurons
• e.g. Neuropeptide Y (NPY), Substance P, Kisspeptin, Enkephalin

Eg. Binding of a ligand then leads to cascades and second messengers

Question 20

What disease is caused by too little dopamine?

Answer 20

Parkinsons

Question 21

What factors determine synaptic action?

Answer 21

1) The type of neurotransmitter/neuromodulator
2) The type of neurotransmitter receptor/channel complex expressed in the
postsynaptic membrane
3) The number of neurotransmitter receptors present in the postsynaptic membrane – ‘ Synaptic plasticity’: Long Term Potentiation (LTP) or Long Term Depression (LTD)

Question 22

Can neurotransmitters bind to different receptors?

Answer 22

Yes.

A neurotransmitter can bind to different receptors and different neurotransmitters can bind to the same receptor

Question 23

Synaptic plasticity

Answer 23

increasing stimulation can lead to an increase of receptors for that signal and thus sensitive( long term potentiation)
But can also downregulate receptors-> less responsive to a stimulus( long term depression)

Question 24

How can neurotransmitter be inactivated?

Answer 24

• Diffusion away from the synapse
• Enzymatic degradation in the synaptic cleft (eg. Acetylcholine esterase degrades Ach)
• Re-uptake for most of the amino acids and amines and re-cycling
Involvement of specific neurotransmitter transporters in the
presynaptic membrane; e.g. glutamate transporters, dopamine
transporters or serotonin transporters

Question 25

Integration of synaptic inputs by neurons

Answer 25

All the signals combine and diffuse down the neuron to the axon initial segment Each individual synapse, when activated, produces only a very small (only ~ 0.1 mV) postsynaptic potentials at the axon initial segment THESE ARE GRADED POTENTIALS potentials decay when they are passively conducted from dendrites In order to depolarise the initial segment to threshold, the EPSPs need to be enhanced

Question 26

Temporal and Spatial summation of postsynaptic potentials at axon initial segment

Answer 26

Temporal- excitatory neuron needs to fire more rapidly/frequently to generate AP(the size of the stimulus depends on the frequency) Spatial- multiple excitatory neurons fire at the same time

Question 26

Temporal and Spatial summation of postsynaptic potentials at axon initial segment

Answer 26

Temporal- excitatory neuron needs to fire more rapidly/frequently to generate AP(the size of the stimulus depends on the frequency) Spatial- multiple excitatory neurons fire at the same time

Question 27

excitotoxicity

Answer 27

Inhibitory neurotransmitters do not work properly ```  Increased release of neurotransmitters  Example: glutamate  This leads to increased Ca2+ accumulation Ca2+ leads to more glutamate  Activates enzymes that kill the cell ```

Question 28

What happens to the neuron when they lack GABA receptors?

Answer 28

- will not respond to GABA - will be more depolarised more +ve - Increase firing of AP - overstimulation- more active

Question 29

Examples of diseases arising from overstimulation of neurons

Answer 29

Schizophrenia | Tetanus: inhibits GABA->paralysis

Question 30

What are graded potentials?

Answer 30

The magnitude of the change in potential is proportional to the signal intensity of the signal or the number of neurotransmitters that bind These are generated at synapses and are then accumulated and diffused down the axon to generate AP