Chemical Signalling for Neurotransmitters Flashcards
What are the different types of synapses?
Synapse: synapto (means clasp)
- Physical connection between them (filaments and scaffolding proteins) not just floating.
Axodendritic: terminal connects with dendrite
Common
Onto dendritic spines (most communication
Sometimes onto the dendritic branch/shaft
Axosomatic synapse: axon to cell body
- Distance from where the input happens relative to the soma influences the firing of the post synaptic cell. All AP are generated at a cell body. Closer input the more strong. - EPSPs and IPSPs can degrade - Axosomatic synapses are more influential
Axoaxonic: axon to another axon
- Two presynaptic terminals which then makes contact with post synaptic cell
- Axoaxonic synapses can reduce transmitter relase onto postsynaptic (presynaptic inhibition)
- Hyperpolarizes the terminal a little bit. Releases less transmitter
- OR depolarizes the terminal, Release more transmitter release.
- Heteroreceptors: relative to the NT in the terminal that they’re on.
○ That receptor responds to a different neurotransmitter that that neuron uses
On a presynaptic terminal activated by a NT that is different from the one used by that neurotransmitter.
What are the different types of common transmitters? How do they work?
Small: aa. Glutamate, GABA, Monoamies (DA, NE, 5Ht, ACH)
Larger: endorphins, CRP and some lipids.
A neuron can have one or multiple transmitters housed in the same terminal We used to think Neurons can have a small molecule and a larger neuropeptide. Released under different circumstances. NOW WE THINK: some terminals contain two small classic ones Ex: some dopamine terminals also have glutamate. Release 2 signals at the SAME TIME. Within terminals: some vesicles that hold small ones, some vesicles that hold neuropeptide Sometimes: a vesicle can hold two small NT at the exact same time.
How are NTs made?
How are they made?
Small: exists within the terminal (everyting you need, converts molecule that you need into NT in the terminal) enzymes that you need are made in cell body and brought to terminal
Large: must be PRODUCED in the cell body (in order to link them together must be in the cell body)
Example: Opiod drugs produced in cell body, transported in terminal, then its broken down into smaller peptides.
Classic vs non classic NTs
Classic: housed in terminal, releases transmitter and works on post synaptic (MOST)
Nonclassic: mostly lipids (retrograde tranmsission) like anandamine (same as marijuana recpeotr) Produced by post synaptic neuron, diffuse out and activate presynaptic neuron receptors.
10 steps of synaptic transmission?
- Nt stored in vesicles
On vesicles there are proteins that allow transmitter to be released
Protect the NT from other enzymes in the terminal- AP comes down invades presynaptic terminal (sodium channels open up and terminal depolarizes)
- Activates voltage gated calcium channels to open (when its depolarized)
- Calcium enters the cell from outside through channels crucial
- Enables vesicles to fuse with presynaptic membrane
Proteins on the vesicles stick out, some designed to stick to other proteins on the release sites. THE ONLY WAY THEY CAN JOIN is if calcium is there! It catalyzes that reaction. Calcium is like Tinder - Vesicles open up and dump though exocytosis release NT
- Bump into NT receptors and change their shape
- Open channels
A. If its metabotropic it activates enzymes (2nd messenger) that does things w ion channels
B. If its ionotropic it opens up ion channels directly and ions will flow in - Hyperpolarize or depolarize.
- Vesicular membrane retrieved and recycled via endocytosis (broken down or use dagain)
MOST transmission happens this way
Whats a NT vs a neuromodulator?
Neurotransmitter: glutamate and gaba always have rapid and consistent signal.
Neuromodulators: don’t have the same effect, enhance reduce or prolong the effect of another neurotransmitter works
- Sometimes excitatory, sometimes inhibitory depending on lots of factors (type of receptor)
- Individual NT has different effects depending on what that cell is doing (when cell is hyperpolarized, its inhibitory and vise versa)
Modulating how other inputs exert their influence.
Not exitatory or inibitory; have different effects depending on multiple factors.
Work on EXTRASYNAPTIC RECEPTORS.
What is volume transmission?
Neuromodulators use this to send a cloud of NT to work on extrasynaptic receptors that aren’t localized.
- influence more than one cell
- influence things that are far away
- influence multiple sites on the same cell
Whats the difference between neurotransmitters and modulators?
Not always clear (classic NT can act as neuromodulators depending on the receptor they interact with)
- Sometimes released as volume transmission (cloud of them away from release point) - Exitatory or inhibitory effect. Lots of NTs we talk about influence other transmitters (often gaba and glut) often suppress or enhance signals on the same cell.
What regulates neurotransmitter release? (what is it influenced by)
Amount of transmitter released is variable. Influenced by
1. Rate and pattern of how its firing
Slow pace, small amount of transmitter, quickly cleared
Faster pace, more release, more influence
Many synapses that come in a BURST pattern lead to MORE firing than rapid continous firing. (even if you give the same number of action potentials)
BURST is a greater signal.
BECAUSE calcium channels respond more to burst patterns.
2. Things that limit the amount of transmitter: AUTORECEPTORS
Receptors for the same transmitter released by a neuron.
Ex: serotonin receptors on same cell that releases serotonin (5ht)
A. Presynaptic terminal autoreceptors (on post and presynaptic)
- These are always inhibitory
- This hyperpolarizes the terminal.
- The next action potential that comes down BLOCKS calcium (by a bit)
- Less and less transmitter release.
B. Somaticdendritic autorecpeptors: located of the cell bodies and dendrites where AP is generated
Is the NT stored in vesicles in the cell body too??
- Activated by same transmitter used by this neuron
- Slows firing rate down
- Reduction in transmitter release.
- Monoamines: when AP is generated at the cell body and it goes down to the axon
□ When they fire, they also release a little transmitter locally around the cell body.
□ Somatic dendritic transmitter release.
□ When it fires, the NT released by the cell bodies activate receptors on the cell body and slow it down.
□ Not so much Gaba and Gluatmate but monoamides do !
What are the effects of targetting autoreceptors?
1. Block autoreceptor: increase in transmitter release. Stimulate autoreceptor (agonist): decrease transmitter release
How are neurotransmitters removed from the synapse?
- Need to detect differences between signals.
- Enzymatic degradation: enzymes in the post synaptic membrane, take NT and break them into components, then uptaken for recycling
- ACH and peptide NTs
- Reuptake: presynaptic terminal has reuptake transporters: take molecules from cleft and suck em in. VERY FAST.
- This is not a terminal autoreceptor. Both reuptake transporters and terminal autoreceptors limit NT in the cleft, but different ways!! They do not effect each other.
- These transmitters wait for NT in the cleft and then take it up - Transmitter reuptake by glial cells: Happens at glutamate and gaba, not localized to terminal, they’re on astrocytes (glial cells)
- Transporters that suck NT into glial cells, then they are put back into presynaptic terminal
- Enzymatic degradation: enzymes in the post synaptic membrane, take NT and break them into components, then uptaken for recycling
Reuptake needs ATP through transporter proteins (against concentration gradient)
- Kind of sloppy - They might also take some other transmitters that are similar in structure - Example: NE transporter, but it also sometimes takes dopamine molecules.
Drugs that block with reuptake will increase transmitter levels.
Its not getting cleared up, so you get accumulation of NT in the cleft.
How do different subreceptor types differ?
All NTs have >1 receptor subtype
2 or more receptor proteins, bind the same ligand, but do different actions. Very similar in amino acid structure. Different in certain parts. Differences in amino acid sequence in their function but same for the ligand they bind.
- Dopamine has 5 easy receptors
- Serotonin has 14 receptors!
1. Different receptor subtypes in different regions of the brain. 2. Different receptors within a brain region In striatum, some medium spiny projections only have D1, and other only have D2 3. Different affinity (different stickiness) D2 has higher affinity for dop than D1 4. Two different receptor subtypes have different effects (one's excitatory and one's inhibitory) - Usually metabotropic receptors, different 2nd messenger cascades. 5. If a receptor is excitatory or inhibitory, what type of neuron is that receptor located on? - How does this effect broad activity - If a receptor depolarizes (excite) if its on projection neurons, net effect is excitatory, but if its on inhibitory interneurons, the net effect is inhibitory. - Its all about the type of neuron too!!
What are the 2 major categories of receptors?
2 major categories
1. Iontropic :ligand gated ion channels 2. Metabotrpic: g-protein coupled, 2nd messengers
Some only work on metabotropic (dop and NE)
Some have receptors that are ion and some that are metabo (glut, gaba, ace)
How are ionotropic receptors made and what do they conduct?
How the receptors are built.
- 4 or 5 subunit proteins - Made separatey and put together. - Proteins in a circle make a little ion channel in the center - Allows different types of ions to pass though
- Some conduct NA (depolarize, AMPA glutamate receptors)
- Some allow Na and CA2+ (NMDA glutamate receptors) Ca2+ entry can
i) depolarize neuron
ii) act as a second messenger - Others conduct cl- (hyperpolarization) Gaba A receptor.
Very fast
How do metabotropic receptors work?
Act more slowly (1 s apposed to ms)
Effects last longer
Long chain of amino acids.
Inserted in membrane with 1 tail end outside, and the chain snakes in and out of the membrane 7 times. 7 transmembrane domain of metabotropic.
On the inside other enzymes might stick to, when the ligand binds it changes configuration and causes g proteins to undock and do their thing.
One side has NT
One side has G protein
When NT binds, G protein released
Activate G proteins that
1) inhibit/activate ion channels directly
2) stimulate enzymes that sythesize or break down second messenger molecules. Cascade to hit other things (DNA, ion channels gene expression)
