Excitation and Inhibition

What’s a gap junction?

• pore that exists between the pre and post synaptic membrane in electrical synapse

• formed by sets of proteins existing in both membranes

• align to create conguate

• 2nm in size

Pros of an electrical synapse?

• fast

more detail

Cons of an electrical synapse?

• not plastic

  • cannot attenuate

General mechanisms of chemical transmission at synapse?

What defines fast neurotransmission?

• ionotropic receptor

• ligand gated by transmitter

• aorund 1 or 2 ms

Mechanisms of fast neurotransmission?

• Transmitter released

• Diffuses across cleft

• Binds to receptors

• These open and allow ions to flow

• EPSP - takes resting potential to more depolarised value

Is an EPSP guaranteed at CNS synapse?

• no

• often require collective effort from many synapses

  • spatial summation (in absence won’t fire)

• in NMJ it is guaranteed

What is the converse of EPSPs and how is it generated?

• IPSP

• hyperpolarising so moving membrane potential further from the threshold for AP generation

What is the common mechanism for IPSPs to be generated?

• influx of chloride ions

• from ionotropic GABAa receptor

What’s another way to make it less liekly to generate an AP?

• increase the amount of conductance for potassium ions

• makes membrane require more current in order to depolarise it

Do axons have one synapse or more?

• can have thousands

• dound along axon like beads on a necklace

• shows how we can compute something complicated

• boutons release the neurotransmitters

What does slow neurotransmission happen from?

• metabotropic G protein couple receptors

What is the synthesis of acetylcholine like?

• Choline is from diet

• Has transporter from blood brain barrier to get in easily

• Use AcCoA with an acetyl transferase enzyme can catalyse the placement of an acetyl group onto choline to reduce to acetylcholine

• Acetylcholine - quaternary amine

What is the storing and releasing of neurotransmitters from vesicles like?

• Dedicated pump in vesicular membrane to get acetycholine in

• Driven by exchange of protons out of vesicel for acetylcholine in

• Proton gradient dependent on ATP …

• Vesicles highly acidic environment

• Pump protons in, hydrolyse ATP

• Exhange protons for acetylcholine

• Influx of calcium drives fusion process

• Liberation into cleft

What is the degradation of neurotransmitters/acetylcholine like?

• Broken down enzymatically

• Choline transported back into pre

• Re-acetylated by the enzyme

• This is unusual - don’t usually break down the neurotransmitter

  • May be because NMJ needs to be broken down because release lots - requires more than just transporters

Picture of the agonists and antagonists of the receptors?

What is main example of catecholamine?

dopamine

What is similar about transmission process for dopamine as acetylcholine?

• loading to vesicles

  • vesicle has proton transport

  • highly acidic

  • requires proton exchange to charge vesicle

  • transporter now transports dopamine

What is the synthesis of dopamine like?

• tyrosine from diet

• tyrosine hydroxylase translates into LDOPA

• then converted to dopamine

Are dopamine receptors ionotropic or metabotropic?

metabotropic

How does break down happen?

pumped back into pre terminal for recharging into vesicle via dopamine transporter

What does monoamine oxidase do?

• breaks down neurotransmitters

• can keep levels of neurotransmitters appropriately regulated

Examples of agonists and antagoists on dopamine receptors?

haloperidol - commonly used in treatment of schizophrenia

Norepinephrine diagram I think?

• converted to NE from dopamine within vesicle not before

Examples of agonists and antagonists for norepinephrine?

What is the precursor for serotonin?

• tryptophan

  • essential amino acid which cannot be synthesised itself so muct come through diet

How is serotonin synthesised?

• tryptophan

• tryptophan hydroxylase

• to 5-HTP

• then carboxylase to 5-HT

Whats a common modification of the 5-HT transporter?

• antidepressants - SSRI eg prozac

• fancy name = fluoxetine

Examples of agonists and antagonists of serotonin receptors?

What is the main excitatory amino acid and how is it made?

• glutamate

• from alpha-kg using aminotransferase

What are the receptors of glutamate like?

• both ionotropic and metabotropic

• principle are NMDA and AMPA

How long does it take glutamate to be transported back into cell?

around 30 seconds so need reserve for about that

What receptor is often found on presynaptic?

• kainate

• autoreceptors regulate transmitter release

Examples of glutamate receptor agonists and antagonists?

• CNQX and NBQX are used in treatment of epilepsy

Whats the main inhibtory amino acid?

GABA

Physiological difference between glutamate and GABA?

GABA is made from glutamate by being acted on by decarboxylase

Which of the two GABA receptors are ionotropic and metabotropic?

• a = ionotropic

• b = metabotropic

Examples of the GABA receptor agonists and antagonists?