Introducing chemical synapses & neurotransmitters

• Chemical synapses 


  • most common type of synapse in mammalian brain
  • can either be excitatory or inhibitory
  • excitatory - post synaptic membrane is depolarised
  • inhibitory - postsynaptic membrane is hyperpolarised
• stage 1 of life cycle of neurotransmitters


  • neurotransmitters are created
  • neurotransmitters are built from precursors
  • precursors are molecules which form the building blocks of neurotransmitters - gained from our diet
• What is stage 2 of the life cycle of neurotransmitters?

  The uptake of precursors
• What does the uptake of precursors depend on?

  The type of neurotransmitter
• Where are small molecule neurotransmitters created?

  At the axon terminal
• Where are neuropeptides made?

  In the endoplasmic reticulum
• How does the uptake of precursors differ for neuropeptides compared to small molecule neurotransmitters?

  Neuropeptides are made in the endoplasmic reticulum and transported to the axon terminal
• What is the process of transporting neuropeptides to the axon terminal?

  They are transported from the endoplasmic reticulum to the axon terminal
• What are the key differences in the synthesis and transport of small molecule neurotransmitters and neuropeptides?

  • Small molecule neurotransmitters:
  • Created at the axon terminal
  • Uptake of precursors depends on the type of neurotransmitter
  • Neuropeptides:
  • Made in the endoplasmic reticulum
  • Transported to the axon terminal
• stage 3 of the life cycle of neurotransmitters

  storage

  neurotransmitters are stored in vesicles

  small molecule neurotransmitters are stored in synaptic vesicles

  neuropeptides are packaged in large dense core vesicles
• stage 4 of life cycle of neurotransmitter

  an action potential arrives at axon terminal

  the voltage gated calcium ions open, which allows for calcium to flood into the synaptic knob

  the flooding of vesicles, allows for vesicles to move towards the presynaptic membrane

  via exocytosis the vesicles release the neurotransmitters into the synaptic cleft

  neurotransmitters diffuses across the synaptic cleft and bind to the receptors on the postsynaptic cell
• stage 5 of life cycle of neurotransmitters

  the neurotransmitter diffuses across the cleft to bind to receptors on the post synaptic membrane

  the neurotransmitter binding to the receptor affects the membrane potential

  if the neurotransmitter causes positive ions to enter the postsynaptic cell, the postsynaptic cell becomes depolarised and more likely to fire an action potential - EPSP

  if the neurotransmitter causes negative ions to enter the postsynaptic cell, the postsynaptic cell becomes hyper polarised and is less likely to fire an action potential - IPSP
• 2 types of receptors

  ionotropic receptor - transmitter gated ion channel

  • directly opens or closes ion channels
  • when a neurotransmitter binds to an ionotropic receptor, the receptor protein changes its conformation which creates an opening for ions to travel through
  • fast effect, local and short term effects

  metabotropic receptor - G protein coupled receptor

  • when the neurotransmitter binds, it activates a G protein
  • it then diffuses inside the cell and binds to the bottom of ion channel, making the channel open from the inside
• stage 6 of life cycle of neurotransmitter

  diffuse out of the synaptic cleft

  re-uptake from axon terminal for reuse

  enzymes
• what determines if the effects on the postsynaptic cell are EPSP or IPSP

  depends on the type of ion channel that is coupled to the receptor

  if the ion channel is for sodium = depolarisation = EPSP

  if the ion channel is for calcium = hyperpolarisation = IPSP
• examples of small molecule neurotransmitters

  acetylcholine

  serotonin

  biogenic amines
• acetylcholine

  used in cholinergic neurone

  at many sites especially in the neuromuscular junction

  binds to nicotinic receptors and muscarinic receptors

  elevating ACh level in the human brain has positive effects on learning and memory

  drugs that temporarily alleviates Alzheimer's increase acetylcholine levels as it suppresses acetylcholinesterase
• how does acetylcholine work in the neuromuscular junction?

  binds to nicotinic receipts which has built in ion channels

  once binding happens, it quickly changes conformation to allow sodium to enter the cell causing depolarisation

  due to the depolarisation neuronal firing causes the muscle to contract
• dopamine

  important in emotion and cognition

  3 main dopamine pathways

  mesolimibc pathway

  • ventral tegmental area of the midbrain, to the ventral striatum
  • strongly implicated in drug abuse and addiction
  • reward and pleasure

  mesocortical pathway

  • VTA to prefrontal cortex
  • planning/STM

  nigrostriatal pathway

  • substantia nigra of the midbrain to the dorsal striatum
  • motor functions
  • parkinson's - loss of dopamine in the nigrostriatal pathway in the midbrain
• serotonin

  precursor = tryptophan - essential amino acid found in grains, meat, dairy and chocolate

  serotonin = produced in the raphe nuclei - brainstem

  proceed widely across the cortex

  implication on mood, sleep, body temperature, appetite and metabolism
• neuropeptides

  larger molecules compared to small molecule neurotransmitters

  more than 100 discovered

  produced in endoplasmic reticulum and stored in large dense core vesicles

  binding has a slow onset effect but a long term

  main categories:

  • brain peptides
  • gut peptides
  • opioid peptides
  • pituitary peptides
  • hypothalamic release hormones
• oxytocin

  famous neuropeptide

  pro social

  love hormone

  implicated in trust in social interactions
• endorphins

  type of opioid peptide

  best understood opioid neuropeptide

  high affinity for and lasting effects on μ-opioid receptors in the brain

  produced by pituitary gland in response to pain and stress but can be triggered by exercise and sex
• how do neuropeptides differ from small molecule neurotransmitters

  NP usually produces a postsynaptic response with a much slower onset but for longer duration

  NP usually binds to a metabotropic receptor

  NP can module effects of another transmitter - neuromodulators