Synaptic integration

1. Synthesis of transmitter substance

2. Storage and release of transmitter

3. Transmitter interacts with the postysnaptic receptor.

4. Transmitter is removed from the synaptic cleft. 

• Transmitter - A substance which is released at a synapse by one neuron and affects a postsynaptic target in a specific manner for a short period.
• Formal criteria for a transmitter:

                      Must be synthesised in a neuron

                      Must be present in the presynaptic terminal and released, giving a defined                                        postsynaptic respone.

                     When administered as a drug, it must exactly mimic a transmitter

                     There must be a mechanism for removing it from the cleft. 

1. Small molecule neurotransmitters - These are amino acid derivatives that are packaged into small synaptic vesicles, but also some dense core vesicles.

                      These affect the excitability of neurons

2. Neuroactive peptides - These are large amino acid polymers packed into dense core vesicles. 

                      These affect the gene expression/synaptogenesis/morphology of neurons

• These are syntehsised at the soma.
• Their exocytosis is not highly regulated, and rapid recycling does not occur.
• Not associated with fast sustained transmission

• Tagging atrial natriuretic factor with GFP shows that the peptide continualy moves up and down the neuron, and is releasd with needed at bouton swirls.
  

• There are three groups:

                     The biogenic amines - E.G serotonin/dopamine

                     The amino acids           E.G. Glutamate/GABA

                     Miscellaneous               E.G. acetylcholine

• Many biogenic amines have a shared synthesis pathway:

                        L-tyrosine -> L-DOPA -> Dopamine -> noradrenaline -> adrenaline

• Depending on what transmitter they release, neurons have different frequencies of the required synthesis enzymes. 

• There are three groups:

                     The biogenic amines - E.G serotonin/dopamine

                     The amino acids           E.G. Glutamate/GABA

                     Miscellaneous               E.G. acetylcholine

• Many biogenic amines have a shared synthesis pathway:

                        L-tyrosine -> L-DOPA -> Dopamine -> noradrenaline -> adrenaline

• Depending on what transmitter they release, neurons have different frequencies of the required synthesis enzymes. 

• Occurs at the synaptic terminal and requires ATP.
• H+ enters the vesicle against its concentration gradient through a v-ATPase. 
• H+ exits the vesicle down its concentration gradient through an antiport transporter, with 2 proteins allowing 1 neurotransmitter molecule to enter. 
• Transporters/v-ATPases are targets for amphetamine and extasy (which depletes 5-HT in vesicles and therefore increases levels in the cytoplasm, allowing calcium independant release of 5-HT.

• Occurs in three ways:

                Diffusion away from the synaptic cleft, called spillover, as the diffused neurotransmitter can activate                                receptors in neighbouring terminals.

                Degradation 

                Reuptake

Reuptake 

• Uses transporters such as Na+ K+ antiport for glutamate (goes in with Na) or Na+ Cl- symport for other neurotransmitters like serotonin or choline (goes in with Na)
• SSRIs like fluoxitine, and also tricyclic antidepressents, block the reuptake of serotonin.
• Cocaine blocks the reuptake of noradrenaline
• Reuptake of acetylcholine works as follows

                Acetylcholine --(acetylcholine esterase)--> Choline + acetate

                Choline reenters the sell by a choline transporter 

                Choline + acetylCoA ---(Choline-acetyl transferase)---> acetylcholine

• Gases can diffuse direcly and so do not need vesicles.
• An example is NO
• It is synthesised from arginine by nitric oxide synthase
•               This enzyme can be activated by the NMDA receptor (activated by glutamate)
•               The NO can cross back over the synaptic cleft in retrograde signalling
•               Its purpose is to activated soluble guanylyl cyclase, which causes GTP -> cGMP
•               It is involved in neuronal plasticity.

• The individual input of neurons is not very significant, the important thing is the collected input.
• The information currency of the neuron is the action potential.
  

• The axon hillock is the integration site - It is called the spike initiating zone as it has a lower threshold than the cell body (+10mV compared to +30mV).
• As it contains the spike initiating zone, there are many voltage gated channels, which is why it is the integration site. 

• The integration is through the passive spread of potential from the post synaptic terminal to the trigger zone in the axon hillock.
• It is influenced by the space and time constant (see earlier notes).

• Two inputs are received at the same site, but only if both are received can an action potential be triggered. 
• If the two inputs are received far apart in space, then decay by the space constant means that there won't be an action potential. 

• This is where a single site is activated twice in short succession and so there is no decay due to the time constant. The larger the time constant the more temporal summation can occur.

• Dendrites can encode the temporal sequence of synaptic inputs.
• Labelling and stimulating dendrites shows that the sequence of stimulation influences the amount of depolarisation. 

• Inhibitory neurons work in conjunction with excitatory neurons, reducing passive depolarisation.
• A large time and length constant means that responses from lots of neurons can be integrated.
• A small time and length constant allows few inputs matched closely in time to be integrated.

• The electrical properties of neurons can be influenced by experience.