synaptic transmission

what are the stages of synaptic transmission?

1. action potential in axon of presynaptic neurone & depolarisation of nerve terminal

2. opening of voltage-gated Ca2+ channels in terminal membrane

3. calcium enters cell

4. secretion of neurotransmitter from vesicles in presynaptic membrane by exocytosis

5. diffusion of transmitter across synaptic cleft

6. some binds to post-synaptic receptors

7. response in post synaptic cell: change of membrane potential in post-synaptic neurone, either depolarised or hyperpolarisation

8. removal of neurotransmitter from synapse: some degraded by enzymes, some taken up by pre synaptic cell (endocytosis), some diffuse away from the synaptic cleft

what are the two main types of receptor?

1. ionotropic

   • fast response: neurotransmitter binds to a channel linked receptor

   • few to a several hundred milliseconds. channel open to allow specific ions through Na+, K+, Cl-

2. metabotropic

   • slow, g protein direct coupling to channel

   • receptors trigger biochemical changes, rather than direct changes in membrane permeability

what is the process of metabotropic receptors?

• g protein activates/inhibits an enzyme that synthesises intracellular molecules which then act on specific intracellular targets

• indirect coupling

what is excitation & inhibition?

• depolarisation = excitation = excitatory post-synaptic potential

• hyperpolarisation = inhibition = inhibitory post-synaptic potential

what are the different effects of synapses?

• some are depolarising, some are hyperpolarising

  • depends on the type of transmitter and receptor

• magnitude varies depending on size & stimulus

what occurs during excitatory synaptic transmission?

• brings the membrane of the post-synaptic neurone closer to the threshold for generation of an action potential

• this depolarisation = EPSP

• EPSPs = are graded, the amplitude of depolarisation increases as more transmitter binds to receptors

• depolarisation is greatest at the site of origin and decreases as it moves towards the axon hillock

• EPSPs can be fast or slow

• last longer than the AP that initiated them, they are also smaller and can be superimposed/added into one another = SUMMATION

what is the process of inhibitory synaptic transmission?

• IPSPs are graded

• neurotransmitter binds to receptor

• channels for either K+, or Cl- open

• if K+ channels opens:

  • K+ moves out → IPSP

• if Cl- channels open

  • Cl- moves in → IPSP

describe synaptic potentials

• graded in intensity

• may be depolarising, or hyperpolarising

• can be fast or slow - slow for important control functions such as cardiac output, secretion of hormones, mood changes, etc.

• as synaptic potentials are graded, they can summate - unlike action potentials

• summation is necessary because a single EPSP is rarely sufficiently large to depolarise the post synaptic neurone to threshold

• two kinds of summation:

  • temporal

  • spatial

what is spatial summation?

balance of all excitatory & inhibitory inputs across dendrites & soma

• A + B = depends on nearly all simultaneous timing of occurrence of two or more separate stimuli

what is temporal summation?

repeated low-level input sums together to cause an output

• consecutive arrival of APs

what is action potential frequency?

determines the amount of transmitter release

• inhibition shapes excitation to modulate activity

how is synaptic signalling mediated?

• neurotransmitters belong to a variety of different chemical classes

  • e.g. acetylcholine, norepinephrine, histamine = excitatory

  • e.g. GABA, glycine, dopamine = inhibitory

describe amplitude

• AP= large, 70-110mV

• graded potential = small, but can summate to result in Ap

describe duration

• AP = brief, usually 1-2 ms

• graded potential = variable, 5ms to minutes

what is an example of fast transmission?

• neuromuscular junction = moto neurones control activity of skeletal muscle fibres (the motor unit)

describe neuromuscular transmission (1)

• AP originates in cell body & propagate along axon & depolarises nerve terminal

• signalling molecule released → calcium & Ca2+ ions flow into the nerve terminal down their electrochemical gradient.

  • local rise in Ca2+ results in fusion docked synaptic vesicles with plasma membrane

• ACh released into synaptic cleft

• ACh diffuses across & binds with nicotine receptors on the post-synaptic membrane

• ion channels open & flow of ions causes Na+ & K+ depolarisation muscle membrane in end-plate region

• when epp at threshold AP generated and propagated down muscle fibre

  • ACh broken down and recycled

• muscle AP causes release of Ca2+ from sarcoplasmic reticulum & triggers contraction of muscle

what agents can synapses be influenced by?

• presynaptic- botulinum toxin - attacks one of the fusion proteins at the neuromuscular junction, preventing vesicles from anchoring to the membrane to release acetylcholine

• post-synaptic - Na+ channels in muscle cells remain open

  • bactrachoTX acts in the open channel and stops it closing - also prevents APs in axons

  • prevent uptake of ACh by the nAChR

what is synaptic modulation?

underlies learning & memory and recovery processes

• presynaptic - modification of the amount of transmitter release

• synaptic cleft - modify reuptake of transmitter

• postsynaptic - greater sensitivity to the transmitter - modify receptor/ion channel