Lecture 29. Synaptic transmission and neural integration Flashcards
what signals are predominant in the mammalian brain?
chemical
in infants- can be electrical
How is a message transmitted between neurons
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
Neuromuscular junction ‘End plate’
the synapse in the muscle fiber
Chemical events of signal transmission
- AP arrives at the presynaptic terminal
- It opens V-gated Ca2+ channels, allows Ca2+ into the terminal
- Ca2+ makes the neurotransmitter vesicles merge with the cell membrane-> release the neurotransmitter into the synaptic cleft
- Neurotransmitter binds to the receptors on the post-synaptic terminal and opens ligand-gated ion channels
- Cations(Na+ and K+) flow
6, This Generates potential in the muscle cell- N-plate potential - N-plate potential will travel both ways and create AP both ways
N-plate potential
the potential( not AP) generated in a muscle fiber (induced by a neuron)
What neurotransmitter is used in muscle?
Acetylcholine
The ONLY one in human neuromuscular junction
What is special about the neuromuscular transmission in humans?
• 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
What diseases affect the generation of AP in muscle fiber?
Myasthenia gravis
Acetylcholine gated channel gets damaged
-> less channels-> End plate potential is not suprathreshold-> AP does not get generated
Are there inhibitory synapses in the neuromuscular junction?
no
2 main types of chemical synapses in CNS
- Excitatory
- Inhibitory
Excitatory synapse
Depolarisation( more +ve) of the postsynaptic membrane called the Excitatory Postsynaptic Potential (EPSP)
Inhibitory synapse
Hyperpolarisation ( more -ve) of the postsynaptic membrane called the Inhibitory Postsynaptic Potential (IPSP)
What are the main neurotransmitters forming an excitatory post synaptic potential(EPSP)
Glutamic acid( glutamate) or acetylcholine(Ach)
What is the mechanism of EPSP?
Transient opening of channels permeable to Na+, K+ and sometimes Ca2+
on the post-synaptic neuron
What is the most common inhibitory neurotransmitter( IPSP)?
GABA or glycine
What is the mechanism of GABA( IPSP)?
transient opening of K+ channels
K flows out-> more -ve inside the cell-> hypopolirazation
2 types of neurotransmitters
Small molecule neurotransmitters ( classical)
Neuropeptide( ‘neuromodulators’)
Small molecule neurotransmitters ( classical)
• Usually fast action (~millisecs) and direct on postsynaptic receptors
- Amino acids: glutamate, GABA, glycine
- Acetylcholine (ACh)
- Amines: serotonin (5-HT), noradrenaline,
dopamine
Neuropeptide( ‘neuromodulators’)
• 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
What disease is caused by too little dopamine?
Parkinsons
What factors determine synaptic action?
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)
Can neurotransmitters bind to different receptors?
Yes.
A neurotransmitter can bind to different receptors and different neurotransmitters can bind to the same receptor
Synaptic plasticity
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)
How can neurotransmitter be inactivated?
• 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
Integration of synaptic inputs by neurons
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
Temporal and Spatial summation of postsynaptic potentials at axon initial segment
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
Temporal and Spatial summation of postsynaptic potentials at axon initial segment
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
excitotoxicity
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
What happens to the neuron when they lack GABA receptors?
- will not respond to GABA
- will be more depolarised more +ve
- Increase firing of AP
- overstimulation- more active
Examples of diseases arising from overstimulation of neurons
Schizophrenia
Tetanus: inhibits GABA->paralysis
What are graded potentials?
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
