What are the 5 stages of neuronal function
1 - Generate intrinsic activity 2 - Receive inputs from other synapses 3 - Integrate received inputs 4 - Encode patterns for output 5 - Distribute outputs to other neurons
Describe the basic features of an electrical synapse
- Direct ionic coupling
– Gap junctions
Describe the basic features of a chemical synapse
- Release of a chemical neurotransmitter
- Diffuses across the synapse
- Interacts with a post-synaptic receptor(s)
- FAST & SLOW chemical transmission (receptor-dependent)
Describe the basic features of a combined synapse
- Some synapses contain both types (e.g., spinal motor neurones in the frog)
What is a gap junction?
- Direct contact between the interior of each cell
- Very small synaptic cleft
- Allows sharing of the cellular contents (ions!)
- Allows very rapid signalling
- Usually (but not always) excitatory
- Present throughout mammalian brain, also retina
- Usually bidirectionality
What is a chemical synapse?
Signal propagation across the synapse by chemical neurotransmitter
How are small molecule neurotransmitters used in synapses
- Synthesised in situ in the nerve terminal by synthetic enzymes
- Final steps of synthesis take place in the vesicle
How are peptide NT (neuropeptides) used in synapses
- Synthesised in the cell body from newly transcribed pre-proproteins by converting enzymes
- Packaged into vesicles in the cell body and transported to the axon terminal
What else is used in synapses
Some may also consider gases (e.g. nitric oxide) and metal ions (e.g. Zn2+) to be neurotransmitters
What are the purposes of the chemical synapse
Information transfer between cells Amplification of signals Integration of multiple inputs Modulation Inhibition Plasticity – learning and memory
Describe small molecules and neuropeptide’s role in nerve propagation at synapse
- Synthesised in the neuron and stored in vesicles – requires precursors and enzymes
- Released in response to depolarisation
- Ca2+-dependent release
- Act at post-synaptic receptor(s)
- Removed by degradation or re-uptake
How is NO different?
Not stored, generated as required, Ca2+-dependent, acts intracellularly, spontaneous breakdown
Name the main small molecule NTs
- acetylcholine, noradrenaline, dopamine, glutamate, GABA etc.
- clear vesicles
- Nerve terminals often contain both types of transmitter
co-expression
Name the main peptide NT
- opioids (endorphins), substance P etc
- Dense core vesicles
- Nerve terminals often contain both types of transmitter
co-expression
Describe small molecule synthesis
Aromatic L-amino acid transporter - tyrosine and Na+ enter - Tyrosine - DOPA via tyrosine hydroxylase - dopamine (DA) via DOPA decarboxylase - noradrenaline (into vesicle via vesicular monoamine transporter (VMAT) via dopamine Beta-hydroxlase
Describe peptide neurotransmitter biosynthesis
From the cell body, mRNA leaves the nucleus and travels to the ER then the golgi, it undergoes proteolytic cleavage (post-transcriptional modification) it then travels down the exon and is released as a dense core vesicle from the terminal
Give an example of peptide biosynthesis
Pre-pro-peptide -> pro-peptide -> peptide
- Pre-proopiomelanocortin
- Preproenkephalin
- Preprodynorphin
Name the opioids and their abreviations
END = endorphin M = methionine enkephalin L = leucine enkephalin NEO = neoendorphin DYN = dynorphin
Describe NO as a neurotransmitter
L-arginine uses Ca+ and nNOS (neuronal nitric oxide
synthase) to change into L-citrulline - releasing NO
This can either be short-lived: rapid spontaneous modification or be used along with guanylate cyclase to convert GTP to cGMP to PKG (protein kinase G)
Used for learning and memory and smooth muscle relaxation
Describe Ca2+ dependant vesicular neurotransmitter release
- An action potential arriving at presynaptic terminal causes influx of calcium ions through voltage gated calcium channels
- Calmodium activates which activates protein kinase II
- PKII phyphorylates Synapsin releasing vesicle from actin cage
- Vesicles move to active zone to be released by exocytosis
- SNARE complex brings membranes tightly together to allow membrane fusion
Describe the signal termination of Ca2+ vesicular NT synapse (3 ways)
1) uptake into glial cell (noradrenaline)
2) re-uptake via transporter into presynaptic membrane (noradrenaline)
3) Breakdown (e.g. acetylcholine by acetylcholinesterase) and recycling for resynthesis
Describe the two major classes of NT action (dependant on receptor type
FAST: - Opening of ion channels - Fast; ms time scale ------EPSP (excitatory post synaptic potential) - depolarisation, +ve in like Na+, increased firing rate ------IPSP (inhibitory post synaptic potential) - hyperpolarisation, -ve in like Cl- or +ve out like K+, decresed firing rates - Ion channels SLOW: - G-protein coupled receptors (GPCRs) - Slow; seconds to minutes time scale - Modulate ion channel behaviour
Give examples of fast and slow
FAST:
- nicotinic acetylcholine
- GABA(little A)
- NMDA (glutamate)
SLOW:
- muscarinic acetylcholine
- adrenoceptors
- GABA(little B)
- metabotropic glutamate
- opioid
