Synaptic Transmission And Intergration Flashcards
What are the 2 types of synapses
Electrical and chemical
Definition of synapse
A specialised junction where an axon terminal contacts another neuron or cell type
What are electrical synapses linked by
Gap junction
What do electrical synapses consist of
Precisely aligned paired channels in pre and post synaptic membranes
What is the gap junction channel formed by in electric synapses
2 hemispheres channels
What is a hemichannel
Connexon
Connexon composed of Connexon subunits
How is the pore of gap junction opened
Connexins rotate
Describe the passage of current in electric synapse
Connexon rotate to open pore in gap junction
Ionic current generated t presynaptic membrane flow passively into post synaptic neuron
Current can pass in both directions (bidirectional/non-rectifying synapse)
Pass in one direction (unidirectional/rectifying)
Rapid and allows ATP and 2nd messenger exchange
Synchronise electrical activity among neuron populations
What are the requirements for chemical synaptic transmission
-Mechanism for synthesising and packing NT into vesicles
-Mechanism for causing vesicle to spill contents into synaptic cleft in response to action potential
-mechanism for producing an electrical or biochemical response to NT in post-synaptic neuron
-mechanism for removing transmitter from synaptic cleft
-must be carried out very rapidly
Describe the synaptic cleft in chemical synapses
20-50nm wide
Held together by a fibrous extracellular matrix
What is the synaptic bouton in chemical synapse
Presynaptic element
Contains synaptic vesicles and secretory granules called large dense core vesicles
What are the membrane differences in chemical synapses
Accumulations of proteins on either side of the synaptic cleft
Active zones - presynaptic site of NT release
Postsynaptic density - contains receptors to translate intracellular signal (NT) into a intracellular signal (chemical change or membrane potential change)
What can synapses be categorised by
Connectivity (which part of the neuron is postsynaptic to the axon terminal)
Synapse anatomy (appearance of the pre and postsynaptic membrane differentiations, size and shape)
Describe axodendritic/axospinous synapses
Postsynaptic membrane on dendrite of another neuron
30% of neurons in the CNS
Describe axosomatic synapses
Post synaptic membrane on cell body of another neuron
6% of neurons in the CNS
Describe dendrodendritic synapses
Dendrites synapse with one another
Rare
Describe axoaxonic synapses
Postsynaptic membrane on the axon of another neuron
Rare
Describe Gray’s Type 1 synapse
Postsynaptic membrane thicker than the presynaptic membrane
Asymmetrical membrane differentiations
Excitatory
Describe Gray’s Type II synapse
Post and pre synaptic membranes similar thickness
Symmetrical membrane differentiations
Inhibitatory
What are synaptic junctions outside the CNS
Junctions between autonomic neurons and glands, smooth muscle, and heart
Describe the neuromuscular junction
Transmission is fast and reliable due to large size with many active zones and a motor end plate with specialised folds for more receptors
One motor neuron innervates one muscle fibre
Only Ach and nicotinic receptors
What are neurotransmitters
Molecules released by pre-synaptic neurons and are the means of communication at the chemical synapse
They are specific for the receptor they bind to and result in either an excitatory or inhibitory signal and can be put into 2 categories based on size (neuropeptides or small molecule NT)
What are neuropeptides
Relatively large transmitter molecules composed of 3 to 36 amino acids
What are small molecule NTs
Include individual amino acids such as glutamate and GABA
Also include the transmitters Ach and the bio genie amines dopamine, noradrenaline, adrenaline, serotonin and histamine
What does fast transmission use
Amino acids or Ach
What does slow transmission use
Any of the three types of NTs
Describe Glutamate
Most common, excitatory in CNS
Iono tropic receptors
Influx of cations into postsynaptic neurons
Metabotropic receptors modulate ion channels
Describe GABA and Glycine
Inhibitory in the CNS
Halfinhibitory synapses in spinal cord use glycine
Bind to ionotropic receptors
Influx of Cl- into post synaptic neurons
Metabotropic receptors activate K+ channels and block Ca2+
Net loss of positive charge
Describe acetylcholine
Used in both PNS ganglia of visceral motor system and CNS, forebrain
Ionotropic receptors - nicotinic
Metabotropic receptors - muscarinic
what are the 5 biogenic amines
Dopamine
Noradrenaline
Adrenaline
Histamine
Serotonin
Describe dopamine
Involved in many forebrain circuits
Associated with emotion, motivation, reward
Acts on G-protein coupled receptors
Excitatory (via D1 receptors)
Inhibitor (via D2 receptors)
Describe noradrenaline
Involved in wakefulness and attention
Acts on the Metabotropic alpha-adrenergic and beta-adrenergic receptors, both of which are excitatory
Describe adrenaline
Acts on the same receptors but its concentration in the CNS is much lower than that of noradrenaline
Describe Histamine
Binds to an excitatory Metabotropic receptor in the CNS and is involved in wakefulness
Describe serotonin
Both an excitatory or inhibitory effect
Involved in a regulation of mood, emotion and several homeostatic pathways
Most receptors are Metabotropic
One ionotropic serotonin receptor which is a non selective cation channel and therefore excitatory
Describe the purine ATP
Cotransmitter
Can be broken down into adenosine, a purine which binds to the same receptors as ATP
Purinergic receptors can be….
Either ionotropic or Metabotropic
Ionotropic receptors are..
Coupled to non-specific cation channels and are excitatory
Metabotropic receptors act on..
G protein coupled signalling pathways
What are neuropeptides
Group of peptides that include molecules involved in pain perception and modulation
Eg substance P, metenkephalin and opioids
Other neuropeptides are involved in the neural response to stress such as corticosteroid-releasing hormone and adrenocorticotropin
Describe ligand (chemically) gated ion channels (ionotropic receptors)
Similar structure to other ion channels and incorporate a ligand binding site (receptor) in the extracellular domain
Control the fastest synaptic events in the NS
Activation generally rapid and is mediated by amino acids and amines
Speed of this response implies that the coupling between the receptor and ion channel is direct
No intermediate biochemical steps involved in transduction phase
NT binding causes channel to open
Consequence depends on specific ions that pass through the pore
Na+ and K+ channels cause depolarisation and are excitatory
Cl- channels cause hyperpolarisation and are inhibitory
GABAa receptor is the site of…
Action of many iimportant drugs and compounds
Barbiturates, benzodiazepines and alcohol cause hyperpolarisation Cl- influx
Describe type 2 G protein couples Metabotropic receptors
Largest super family of receptors
Despite diversity of signal molecule they all have a single polypeptide chain that threads back and forth
Describe the action of G protein coupled receptors
Either by:
- opening ion channels
- by activating enzymes that synthesise second messenger molecules. Tend to be slower, longer lasting and have greater diversity than ligand gated ion channels
Ligand may bind to a family of receptors with different effects due to specific receptor type
What is the role of G proteins
Membrane resistant proteins
Recognise activated GPCRs ad pass on the message
How do G proteins carry out their action?
-Composed of 3 subunits, alpha beta gamma
-Achored to the membrane and coupled to the G protein through prenylation
-Freely diffusable within the plane of the membrane
-Interact with several receptors and effectors
-Unstimulated the a subunit has GDP bound (idle)
-Signal causes α subunit to exchange GDP for GTP
• Α subunit & GTP detaches from βγ complex
• The released α subunit and βγ complex are active
• Diffuse within the membrane and interact with target proteins relying signal to other parts of the cell.
• Βγ mediated effects occur at higher levels of receptor occupancy
• α subunit association with target enzymes cause activation or inhabitation
• Signal terminated when α subunit GTP is hydrolysed to GDP (GTPase)
• Self limiting
• Single receptor agonist complex can activate several G-proteins to produce product molecules
• Product molecules often a second messenger
How to modulate synaptic transmission in progress
Limit further release of transmitter
May act as a break on the release of NT
example of auto inhibition
Noradrenaline in sympathetic neurons
Synthesis and storage of NTs
- Vesicle and peptide NT precursors and enzymes synthesised in the cell and are released from Golgi
- Vesicles travel through the axons on microtubule tracks via fast atonal transport. Peptide NTs are already in some vesicles
- A non peptide NT is synthesised in the nerve terminal and transported into a vesicle
Why must NTs be cleared from the synapse
To permit another round of synaptic transmission
How are NTs cleared from the synapse
Diffusion
Enzymatic degradation in the synapse
Presynaptic reuptake followed by degradation or recycling
Uptake by glia
Uptake by the post-synaptic neuron and desensitisation
NTs in the CNS can act on numerous…
Subtypes of receptors
Low-frequency stimulation…..
Low-frequency stimulation preferentially raises the Ca2+ concentration close to
the membrane, favoring the release of transmitter from small clear-core vesicles
docked at presynaptic specializations. High-frequency stimulation leads to a more
general increase in Ca2+, causing the release of peptide neuro transmitters from
large dense-core vesicles as well as small-molecule neurotransmitters from small
clear-core vesicles.
Describe synaptic integration - inhibition
IPSP are generated when ion channels are opened casing hyperpolarisation of the membrane ie GABA or glycine opens Cl- channels
Shunting inhibition - inward movement of Cl- anions will negate the flow of positive ions
Describe the generation of excitatory postsynaptic potential
- An impulse arriving in the presynaptic terminal causes the release of NT
- Molecules bind to transmitter-gated ion channels in the post synaptic membrane. If Na+ enters the post-synaptic cell through the open channels., the membrane will become depolarised
- The resulting change in membrane potential (Vm) are recorded by the microelectrode in the cell , is the EPSP
What are 2 excitatory NTs
ACh and glutamate
Describe the generation of an Inhibitory Postsynaptic Potential
- An impulse arriving in the pre-synaptic terminal causes the release of NT
- The molecules bind to the transmitter-gated ion channels in the post-synaptic membrane. If CL- enters the post-synaptic ell through the open channels, the membrane will become hyper polarised
- The resulting change is the IPSP
