Animal Physiology Synapses

Chemical vs. Electrical Synapses

Chemical: involve the release of neurotransmitters into synaptic cleft

• have very defined presynaptic terminal full of vesicles with neurotransmitters in them

• released to postsynaptic cell/density via exocytosis where ionotropic or metabotropic receptors await

Electrical: gap junctions

• Connexon proteins make gap junctions to form channels between presynaptic and postsynaptic cells

• presynaptic and postsynaptic aren’t as defined (hard to tell which is which)

• Super fast way to get a signal from one cell to the next but disadvantages include that you lose some of the signal strength and there is less room for modulation

Why is the synaptic cleft so small?

release of neurotransmitters between the cells relies on diffusion so having a small distance to travel is important

What is the equilibrium potential for calcium and why is that significant?

+140 mV

there is a large driving force on calcium to come into the cell and there are a lot of voltage-gated calcium channels found in the presynaptic terminal because calcium is required to help vesicles fuse with the membrane

Receptors types on postsynaptic cell/density

Ionotropic: ligand-gated ion channels

• neurotransmitter (i.e. acetylcholine) binds to receptor on outside of the cell and then the receptor channel opens and sodium flows in

• very fast/almost immediate response

• results in a graded potential inside the cell

• not much room for modulation

• **neurotransmitter does not go through the channel, it just gates it

Metabotropic: G-protein coupled receptors, tyrosine kinase (if receptor is also an enzyme), etc.

• amplifies signal inside the cell; activates 2nd messenger cascade(s)

• few neurotransmitters are needed for a big response

• more room for modulation of the final response inside the cell

Steps for Chemical Synapse

1. Action potential depolarizes the terminal via voltage-gated Na⁺ channels

2. Voltage-gated Ca2+ channels open

3. Vesicles fuse

4. Neurotransmitter diffuses across the cleft

5. Neurotransmitter binds to receptor on postsynaptic cell

What is the distinct difference that you can tell between presynaptic and postsynaptic cell?

The presynaptic cell has vesicles filled with neurotransmitters

What is the main docking protein found on the presynaptic terminal plasma membrane?

Syntaxin

What does calcium bind to when triggering exocytosis of vesicles?

Synaptotagmin

-The ligand binds, changes confirmation, pulls on the other proteins, starts a cascade of other proteins changing conformations and triggers exocytosis

Why must vesicles be recycled after fusing with the presynaptic membrane?

if not, then the synaptic terminal would continue to grow in size due to the incorporation of the vesicles into the membrane

-recycling them allows us to reuse later on to package more neurotransmitter

2 methods for recycling vesicles

-Clathrin-mediated endocytosis: completely fuses with the membrane and then undergoes endocytosis back into the presynaptic terminal

• allows for more neurotransmitter to be released

-Kiss & Run mechanism: transient release of neurotransmitter and then pinches back up into the cell for recycling

• disadvantage is you could be pinching shut before all of the neurotransmitter gets out (so less is being released)

Two methods for removing neurotransmitters from the synaptic cleft

-use enzymes to degrade neurotransmitters (i.e. acetylcholinesterase)

-reuptake: transport neurotransmitter back into the presynaptic terminal to be recycled into new vesicles

What happens with calcium when an action potential stops?

-calcium stops flowing into the cell because the voltage-gated channels close

-the calcium that is in the cell is pumped out to decrease calcium levels which stops vesicles from being released

What must the postsynaptic cell have to terminate signal/stop intracellular cascades?

intracellular mechanisms like phosphatases and kinases to break down/inactive signal effects (2nd messengers)

Glutamate

major excitatory neurotransmitter in the CNS

-also main sensory neurotransmitter in vertebrates

GABA

main inhibitory neurotransmitter in the brain

Glycine

inhibitory

Biogenic Amines

-Dopamine: involved in reward pathways

-Serotonin (5-HT): involved in social behavior and aggression

-Octopamine: the invertebrate equivalent of dopamine

-Acetylcholine: found at neuromuscular junction in vertebrates

-Epinephrine/Norepinephrine: neurotransmitter in sympathetic nervous system (fight/flight)

Vasopressin

Neuropeptide involved in water balance

Neurotransmitters are…

evolutionarily ancient and highly conserved

*their receptors are as well

What is true of glutamate and acetylcholine in invertebrates?

Their roles are opposite of those of vertebrates

-glutamate: muscular

-acetylcholine: sensory

EPSP

excitatory postsynaptic potential

-depolarizes the cell and brings it closer to threshold (closer to firing an action potential)

-easy to get via ionotropic receptors (gated sodium channels)

IPSP

inhibitory postsynaptic potential

-hyperpolarzies the cell and takes it further away from threshold (decreases the likelihood of firing an action potential)

-easy to get with metabotropic receptors activating potassium channels

Temporal vs. Spatial summation

temporal: same stimuli in high frequency that sum over time

spatial: different stimuli summing at the same time

What is true of EPSPs and IPSPs when they occur at the same time?

they can add together and have the possibility of canceling each other out

Will axosomatic or axodendritic synapses have more voice?

Axosomatic you dumbass bitch

a synapse right on the soma is going to have more a a voice because it gets processed faster than a synapse out on the dendrites

Presynaptic inhibitory modulation

inhibition axon cell makes a synapse right on the axon terminal of the other presynaptic cell

-because it is inhibitory, you often have a lot of potassium coming out for a hyper polarizing effects so the actual postsynaptic cell in question doesn’t hear anything

• as far as the postsynaptic cell is concerned nothing ever happened

Convergence

when lots of cells talk to one single cell

ex. Perkingee cell: found in cerebellum with huge dendritic trees; completely 2D, parallel fibers run perpendicular to perking cells that makes synapses with the cell

• important for motor control and motor learning (i.e. riding a bike)

Divergence

one cell that talks to a lot of postsynaptic cells

Which type of synapse has more room for modulation?

chemical synapses

Changing the amount of neurotransmitter released modulation

-presynaptic modulation for a stronger or weaker response

-we change how many vesicles are docked or when we deplete vesicles

• fewer vesicles=weaker response

• more vesicles/pack them fuller=stronger response

Neurotransmitter clearance/reuptake modulation

presynaptic modulation

-add more enzymes to degrade neurotransmitters and weaken the response

-block reuptake transporters strengthens the response (i.e. SSRIs)

Receptor number modulation

postsynaptic modulation

-increase the number of receptors to strengthen

• up regulation: put more receptors on the surface to increase signal response

-endocytose and decrease number of receptors to weaken

• down regulation: take in receptors

Receptor efficiency modulation

postsynaptic modulation

-add or remove groups on receptors transcriptionally to affect strength of receptors

what the fuck is a dumbass Agonists you bitch

chemicals that make synapses stronger

-ethanol: agonist at inhibitory neurons

-morphine: endogenous opiate receptors

Antagonists

block synapses

-tetrodoxin: pufferfish toxin; bacteria symbioses make it; targets voltage-gated sodium channels so it is incredibly potent

-tetanus toxin: targets neuromuscular junction; blocks synaptic release in the presynaptic inhibition cell so there is less inhibition which causes the muscle cell to be overstimulated (i.e. lockjaw and tetanic paralysis)

-botulism toxin: comes from injections or badly canned food; blocks synaptic release at motor neuron presynaptic terminal causing flaccid paralysis

Down regulation

if you overstimulate of synapse, the postsynaptic cell modulates signal strength by decreasing the number of receptors in the postsynaptic density

-cocaine: increases the amount of dopamine so postsynaptic cells begin to take away dopamine receptors (why addicts use more and more)

-insulin

Up regulation

increasing the number of receptors when you aren’t getting enough stimulus to make more of a response from the little neurotransmitter that you are getting

-Naloxone: can lead to super sensitivity due to the up regulation of opioid receptors; overdose on opioids because you increased receptor sensitivity

Aplysia

sea slug invertebrate that has a sensory neuron that innervates the skin

-when you poke the gill, it makes synapses directly on the motor neuron to activate the muscle to pull the gill in as a protective mechanism

-the more you poke, the more the response goes down (habituation)

• this resets when you go poke something else (i.e. tail) because facilitating interneurons release serotonin and rests

much of what we know about synaptic plasticity is from this

What happens to calcium channels when there is habituation?

voltage-gated calcium channels are inhibited so there is not a lot of vesicle release and the motor neuron stops firing

What happens during sensitization with the Alysia slug?

serotonin (5-HT) from the tail causes a decrease in the potassium current and that allows the calcium channels to stay open longer despite the inhibition

What kind of mechanism is habituation and sensitization?

presynaptic mechanism

What kind of mechanism in long term potentiation?

postsynaptic mechanism

What structure of the brain is involved in long term potentiation in mammals?

hippocampus

What neurotransmitter is involved in long term potentiation and how does this synapse function?

glutamate

-glutamate is released and binds to ionotropic receptor to allow sodium in

• AMPA receptor

-glutamate also binds to calcium channel but it can only flow through if magnesium ion is popped out by the EPSP that was initiated by the sodium current

• NMDA receptor

• activates Ca2+ second messenger cascade and brings about release of nitric oxide

What works to maintain the structure of the axon and axon terminal?

cytoskeleton microtubules and actin

-bridging proteins will sometimes hold pre and post synaptic cells together to keep them close

How does the mushroom-like shape of dendritic spines affect them?

gives them a stronger structure to better promote the effectiveness of the synapse (strengthens it)

-spine grows during times of learning

-strength of synapse can be determined by looking at dendritic spine size and structure