NEUROTRANSMISSION + MODULATION Flashcards
Structure of a Neuron
Dendrites -> recipient of information from other neurons. Soma -> cell body contains the machinery that controls processing in the cell and intergrates information. Axon -> carries info from soma to the terminal boutons. terminal boutons -> found at the end of the axon, location of the synapse, communication point with other neuron
Neuronal membrane
boundary of soma, dendrites, axon, and terminal boutons separate the extracellular environment from the intracellular environment
Neuronal membrane structure
lipid bilayer (5nm) and protein structures. detects substances outside cell, allows access of certain substances into the cell (gated -> chemical or electrical) - cytoskeletal
Two different types of synapse
electrical synapse, chemical synapse
electrical synapse
very rare in adult mammals. found in retina. junction between neurons is very small. gap is spanned by proteins (connexins) which are used to communicate between the neurons (ions move freely).
Chemical Synapse
more common in mammals, junction between neurons longer, chemicals (neurotransmitters) are released from the presynaptic neuron to communicate with the post-synaptic neuron
Early work for chemical transmission
Loewi in 1920s -> application of fluid following vagus nerve stimulation slowed down heart rate,
What are different types of chemical synapses
axodendritic, axosomatic, axoaxonic
Chemical Synapse overview
neurotransmitter synthesis, transport, storage. depolarisation (action potential), open voltage-gated Ca+ channels, Ca+ influx, movement + docking of vesicles, exocytosis -> diffusion, interact with receptors, in/deactivation of neurotransmission.
Neurotransmitters
chemical that is used to transit information from the post-synaptic neuron to the post-synaptic.
Criteria for neurotransmitter
chemicals synthesised pre-synaptically, electrical stimulation leads to release of the chemical, chemical produces physiological effect, terminate activity.
Ionic receptor
opening of an ionic channel (typically). fast transmission leads to an immediate change in the post-synaptic cell.
Metabotropic receptor
activates an internal second messenger, indirectly affects function of post-synaptic cells.
Receptors vary in their:
pharmacology -> how drugs interact w specific receptors. agonist -> a drug producing cellular reaction. antagonist -> drug that reduces or completely blocks the activity of the agonist
Categories of neurotransmitters
Classical, Neuropeptides
Classical Neurotransmitters
amino-acid fast transmission (e.g., GABA and glutamate). monoamines (e.g., dopamine, serotonin), acetycholine. releases in local increase in Ca+
Neuropeptide transmissions
endorphin, pain relief etc. more intense stimulation necessary to release neuropeptides, more increase in Ca+. other small molecules (e.g. nitric acid).
Excitatory fast transmission
Ion channels open, movements of Na+ into the neurone. (e.g. glutamate receptors), depolarisation, excitatory post-synaptic potential (EPSP).
Inhibitory post synaptic potential (IPSP)
Ion channels move, movement of Cl- (e.g., GABAa receptors), hyperpolarisation, inhibitory synaptic potential
Metabotropic receptor
G-protein receptors in the intracellular side
Metabotropic receptor process
neurotransmitter binds to receptor and activates the G-protein (exchange GDP for GTP), G protein splits and activates into enzymes. the breakdown of GTP turns off G protein activity. Series of chemical reactions that leads to an amplification of the signal - second messenger system
Amplification
It is slower but it has a domino effect -> slow but bigger effects. Can activate multiple g-proteins and amplify the effect. Cascade of effects. Slower than inotropic receptor but bigger effect.
Neurotransmission deactivation
Neurotransmitters must be inactivated after use to remove them from the synaptic cleft. They use the reuptake transports. Also have deactivating enzyme and hydrolase the neurotransmitters. Both do the same things in different ways.
Autoreceptors
regulates synaptic transmission. Located on the presynaptic terminal, Respond to neurotransmitter in the synaptic cleft. Generally, they are G-protein coupled. don’t directly open ion channels. Regulate internal process controlling the synthesis and release of neurotransmitter. Negative feedback mechanism. Auto receptors are not the same as reuptake sites!
What is glutamate?
Major fast excitatory neurotransmitter in the CNS. Very widespread through the CNS. Activates different types of receptors -> mGLuR, NMDA, AMPA, Kainate.
Glutamate synthesis process
Synthesized in nerve terminals from glucose or glutamine. Loaded and stored in vesicles by vesicular glutamate transporters. Released by exocytosis (Ca+ dependent mechanism). Acts at glutamate receptors on postsynaptic membrane
Reuptake by excitatory amino acid transporters (EEATs) in the plasma membrane of presynaptic cell and surrounding glia
Different receptors for glutamate
Based on their pharmacology – three types of ionotropic receptor have been described that respond to glutamate
NMDA, AMPA, and Kainite ->
They are named based on the agonists selective for them.
What is AMPA receptor
Ionotropic receptor -> Binding of glutamate leads to the opening of a Na+ channel (slight K+ permeability) and hence depolarization. Selective agonists -> AMPA. Antagonist -> CNQX, DNQX
NMDA receptor?
Ionotropic receptor -> permeable to Na+, K+ and Ca2+, Binding of glutamate -> nothing happens!, Voltage dependent blockade.
Resting membrane in NMDA
At resting membrane potential (-65mV): Glutamate binds, Channel opens. Blocked by Mg2+
Depolarised membrane in NMDA receptor
At depolarised membrane (-30mV), Mg2+ pushed out of pore, Channel is open, Ion movement, Further depolarization, Different ‘kinetics’ from AMPA receptor (open much longer)
Features of AMPA receptor
AMPA (and kainite) receptors -> Fast opening channels permeable to NA+ and K+ (it is a glutamate receptor)
