SignalTransmission between neurons Flashcards
What are the 2 categories of synaptic transmission?
- Electrical
- Chemical
Where are electrical synapses found?
Muscles, glial cells and certain neurons requiring a coordinated response
Describe the structure of electrical synapses
- Intercellular space narrows to form gap junctions
- Gap junctions formed by 2 conexons of 6 connexins
- small molecules e.g ions, can pass
How can electrical synapses between horizontal cells be inhibited?
Dopamine
What are the characteristics of electrical synaptic transmission?
- Fast
- Loss of voltage
- Bidirectional (exitatory and inhibitory)
- Graded
What are the characteristics of chemical synapses?
- Presynaptic vesicles filled with vesicles
- Postsynaptic membrane
- Small synaptic cleft
What are the 4 types of chemical synapse?
- Axo-dendritic
- Axosomatic
- Axoaxonic
Describe type 1 chemical synapses
- Round synaptic vesicles
- Dense basement membrane
- Large active zone
- Large post-synaptic density
Describe type 2 chemical synapses
- Oval synaptic vesicles
- Shallow basement membrane
- Small active zone
- Small post-synaptic density
Name the classical neurotransmitters
Amino acids - Glutamate - GABA - Glycine Amines - Ach - Dopamine - Serotonin
Name non-classical neurotransmitters
- Neuropeptides
- Neurotrophins
- Gaseos massengers
- D-serine
- Endocannabinoids
- ATP/adenosine
What are the two neurotransmitter synthesis methods?
- Neuropeptides broken down from precursor proteins after being synthesized. Packaged and processed in the Golgi aparatus and stored at the presynaptic terminal
- Precursors combine with enzyme to form neurotransmitter
How are neurotransmitters transported to the pre-synaptic membrane?
Require special transporter proteins on vesicle membranes
How are neurotransmitters released from the pre-synaptic membrane?
- Action potentials open voltage-gated Ca2+ channels
- Binding of synaptotagmin triggers fusion of neurotransmitter vesicle
- Activates Ca/Calmodulin dependent kinase II which acts on synapsin so more vesicles dock at the active zone
What are the two different types of receptors?
Ionotropic and metabotropic receptors
Describe ionotropic channels
- Ligand-gated channels
- Extracellular neurotransmitter binding domain and membrane-spanning ion channel
Name 4 different ionotropic receptors
- Nicotimic AChR
- AMPA Glutamate receptor
- NMDA Glutamate receptor
- Glycine receptor
What is an agonist and antagonist?
Agonist - substance that binds to neurotransmitter receptors and mimics neurotransmitter actions
Antagonist - bind to but do not activate transmitter receptors, blocking the actions of neurotransmitters
What are EPSPs and what are they mediated by?
Lead to depolarisation of membrane potential, usually mediated by Ca2+ influx , causing post-synaptic neuron action potential
What are IPSPs and what are they mediated by?
Lead to hyperpolarisation of the membrane potential making it more difficult for the post-synaptic neuron to fire action potentials, mediated by Cl- influx or K+ outflow
What is synaptic delay?
Delay in change of post-synaptic membrane usually ~ 1ms
Describe metabotropic receptors
Alter intracellular metabolic reactions, often stimulate the production of second messengers (G-protein, cAMP, diacylglycerol), which in turn activate protein kinases, phosphorylating different substrate
proteins including ion channels
Which neurotransmitters have metabotropic receptors?
Glutamate, Adrenaline/noradrenaline, most seretonegic neurons all neuropeptide receptors
What are neuromodulators?
- Work via metabotropic receptors
- Can’t send fast transmission on their own but can alter fast synaptic transmission
- Receptors can be pre/post synaptic
Describe muscarinic Ach receptors
1,3 and 5 - excitqatory, coupled to PKC leading to increase in Ca2+ causing smooth muscle to contract
2,4 - inhibitory, inhibit cAMP production and open K+ channels slowing down heart rate
Describe what receptors peptide hormones may bind to and what effects these induce
G-coupled proteins or Receptor tyrosine kinases can activate
- MAPK (differentiation and plasticity)
- PLC alpha
- PI3-Akt which promotes cell survival
What are
a) autoreceptors
b) heteroreceptors
a) receptors on presynaptic terminals activated by own transmitter
b) activated by transmitters different to their own
Both typically metapotropic
Give an example of a system with auto and heteroreceptors?
Histaminergic system
These can occur on non-histaminergic cells
Name 2 presynaptic mechanisms of inactivation of a chemical transmission
- Reuptake by transporters (dopamine, serotonin)
- Binding of inhibitory autoreceptor at presynaptic membrane inhibiting exocytosis (GABA, glutamate)
Name 3 methods mechanisms of inactivation of a chemical transmission occuring in the synapse or involving glial cells
- Diffusion from the synaptic cleft
- Uptake by glial cells (glutamate, GABA)
- Enzymatic decay of neurotransmitter (e.g Ach is broken down by AchE to acetate and choline, pumped by choline transporter)
Name 2 postsynaptic mechanisms of inactivation of a chemical transmission
- Internalisation of receptors
- Desensitization of receptors
Describe the breakdown of glutamate
- Internalised by astrocytes, broken down to glutamine by glutamine synthase and transported back to the neuron by glutamine transporters
- recycled into glutamate by glutaminase
Describe the mechanism of temporal integration
- 2nd PSP rides on the back of the 1st one to become more effective
- Currents flowing across membrane determined by post synaptic time constant, PSP dynamics and presynaptic firing frequency
Describe the mechanism of spatial integration
- Arrival of 2nd input coincides with 1st
- More currents flowing across membrane. Determined by postsynaptic length constant and distance between inputs
What is a signal process and where are they typically found?
- Receive both excitatory and inhibitory inputs
- Used in locomotion and processing of cyclic inputs
What is short-term facilitation?
- Where the 2nd PSP is larger
- Can be due to accumulation of Ca2+ in presynaptic terminals, increase in reusable vesicles and/or calcium channel facilitation
What is short-term anti-facilitation?
- 2nd PSP is smaller Could be due to: - Depletion of presynaptic veiscles - Desensitization of receptors - Saturation of postsynaptic receptors - Negative feedback of autoreceptors
What is Hebbian long term potentiation?
After simultaneous firing of pre and post synaptic neurons EPSPs are enhanced
Describe an example of early phase long term potentiation
- Ca2+ increase causes retrograde messengers to enhance neurotransmitter release
- New AMPARs are inserted into postsynaptic membrane enhancing affinity for glutamate
What occurs during late phase long term potentiation?
- Transcription of new genes and synapse formation
- Can involve CAMP pathway and cAMP kinase activation
What is non-hebbian long term potentiation?
- Does not require both pre and post synaptic activation
- Occurs via the activation of G-proteins and protein kinases
What is long term depression?
- Where synaptic transmission becomes weaker over time after conditioning stimulation
- Uses internalisation/desensitization of AMPARs
What is a neuromuscular junction?
Synapse between muscle and motor neuron
Describe the strucute of a neuromuscular junction?
Motor neuron innervates muscle membrane at end plate, where axon looses myelin sheath and splits into many branches called synaptic boutons which transmit at junctional folds containing receptors
What neurotransmitter is released by motor neurons?
Acetylcholine
How does a motor neuron excite a muscle fibre?
- Release of neurotransmitter opens postsynaptic Ach receptors
- Causes EPSP (or end plate potential) which if compound EPSP (from many boutons) is large enough opens v gated Na channels causing action potential which spreads along the muscle fibre
Describe the stucture of a synaptic bouton
- Contains multiple release sites each capable of releasing neurotransmitter
What is quantal release?
- Neurotransmitter released in discrete ammounts called quanta
- Each produces post synaptic potential of equal size called the quantal synaptic potential
- Causes smooth grading of total EPSPs
Give an example of a non-spiking synapse
- Photoreceptor bipolar cell
- Glutamate released at base level causing continuous depolarisation (-40mV)
- Post-synaptic response is not linear
What are voltage dependent NMDARs?
- Have multiple binding sites for neuromodulators as well as glutamate
- Mg binding site present inside which is blocked at hyperpolarisation which can be removed by depolarisation
- Need both post and pre synaptic neuron to fire
- If you change voltage level changes size of EPSPs
- Important in long term potentiation
What neurotransmitter have been shown to be released by glial cells?
Glutamate, ATP-adenosine, D-serine
How do gial cells enact transmission?
- Have some receptors which can be activated
- Release neurotransmitters which act very locally on neurons
Give an example of gial transmission
hippocampal CA3–CA1 synapses
- Glial glutamate activates presynaptic groups
- Glial adenosine activates postsynaptic receptors
- Changes transmitter release and contributes to LTP
Which transmitters can enact retrograde signalling?
Lipid derived (endocanabinoids) Gases peptides GABA Growhth factors
How does retrograde signalling enact long term potentiation?
e. g Ca2+ influx through NMDAR
- Ca2+/Calmodulin activates NO synthase
- NO released
- Activates presynaptic guanylate cyclase
- Results in cGMP enhancing vesicle release
- PDE can degrade cGMP stopping the enhancing process
Describe presynaptic inhibition
- Neuron inhibited causing increased Cl- conduction and less Ca2+ entry
- Less vesicle release therefore less postysynaptic EPSP
Describe presynaptic facilitation
- Neuron activated causing K+ current to become depressed
- More Ca2+ entry and more vesicle release -> bigger postsynaptic response
Describe reciprocal inhibition
Present in neurons controlling antagonistic muscles
What is recurrent inhibition?
- Where neurons inhibit themselves in a negative feedback fashion
What are reciprocal excitations?
Mechanism for maintaining long-lasting neuronal activities such as eye movements, posture and locomotion
