Plasticity II

What is Gs responsible for?

activating PKA via a cascade

What is Gi responsible for?

inactivating PKA

How many subunits does PKA have?

2 catalytic
2 inhibitory

When all 4 subunits are bound together on PKA the enzyme is?

turned off

What does the alpha subunit activate?

adenylyl cyclase

What does adenylyl cyclase convert?

ATP to cAMP

What do the cAMP molecules do?

bind to the regulatory subunit to dissociate the catalytic subunits from the inhibitory subunits

What do the catalytic subunits do?

phosphorylate the K channel to close it

A big benefit of metabotropic receptors (like the Gs G protein) is what?

signal amplification

How does signal amplification occur in G-proteins?

when one G protein is no longer associated with the receptor another can associate and turn on

one adenylyl cyclase can make lot’s of cAMP

each cAMP molecule can turn on many PKA’s
each PKA can phosphorylate a lot of channels

What is aplysia?

a sea slug

How did we figure out so much about learning and memory on the cellular level?

by studying the simple circuits of aplysia

Who worked with aplsyia?

Eric Kandel

What is the main focus point of the sea slug?

its gill withdrawal reflex

What happens if you (physically) touch the sea slug’s siphon?

it withdraws the gill as a defensive mechanism

What sensitization?

to make something stronger

A single ________ ______ to the tail causes an even larger withdrawal in sea slugs.

electric shock

What kind of withdrawal occurs when you’ve already touched the siphon once, then shocked the tail, then touch the siphon again?

a very strong withdrawal (similar to the tail shock)

Draw the circuit for the gill withdrawal reflex.

siphon, siphon sensory neuron, motor neuron, gill musculature, tail, tail sensory neuron, serotonergic facilitating interneuron

What is the main area of focus within the gill withdrawal reflex circuit?

where the siphon sensory neuron, serotonergic facilitating interneuron, and motor neuron come together

What happens to the AP after tail shock? (draw before + after)

it is longer

What happens to the EPSP in the motor neuron after the tail shock? (draw before + after)

it is taller and longer

What occurs after shocking the sea slug tail?

1) sensory neuron activates

2) facilitating neuron releases serotonin
3) AP causes motor neuron to activate, causing gill withdrawal

(all events occur at the same time)

Why do we get a longer, broader AP if we touch the tail after shocking it?

because the K channels are closed, allowing more Ca to enter the presynaptic terminal, causing a longer depolarization

When S-type K channels are phosphorylated, they are what?

closed

What does a longer depolarization allow?

more calcium influx, hence more NT release

What causes the AP to become broader (sea slugs)?

serotonin

How does serotonin cause the AP to become broader?

it triggers a metabotropic cascade that closes the K channels, causing a larger depolarization

Is the sensitization of the gill withdrawal reflex permanent or temporary?

temporary

What type of channels are affected by serotonin?

S-type K channels

What type of GPCR does serotonin use?

Gs

What are endocannabinoids?

naturally produced cannabinoids

How many natural cannabinoids are there?

2

What receptors in the brain bind endocannabinoids?

CB1 receptors

Where are CB1 receptors found?

in the presynaptic terminals all over your brain

What type of receptors are CB1?

metabotropic GPCRs

What triggers the synthesis of endocannabinoids?

Ca

Calcium activates enzymes that synthesize endocannabinoids from what in the cell’s membrane?

lipid precursors

Because they are lipid based molecules, they can do what easily?

cross the cell membrane (do not need to be released in a singular manner like other transmitters)

What happens when endocannabinoids diffuse out of the cell?

they can bind CB1 receptors, liberating the beta-gamma subunit, blocking synaptic calcium channel

What makes a transmitter retrograde?

when it goes from the postsynaptic cell to the presynaptic cell

What happens if a few endocannabinoids are bound to CB1 receptors?

smaller postsynaptic response

What happens if we generate enough endocannabinoids to block all of the Ca channels?

no postsynaptic response

The suppressive effects of endocannabinoid signaling were shown by a phenomenon called what?

depolarization induced suppression of inhibition

In the hippocampus and cortex, CB1 receptors are found only on the terminal of ________ axons.

inhibitory

All contacts on dendritic spines are what?

excitatory

What happens when inhibitory and excitatory axons fire simultaneously?

weak response because inhibitory inputs largely cancel out excitatory inputs

What happens when you only activate the excitatory axons?

a large depolarization because the inhibitory axons aren’t countering it

Why does inhibition cancel some of the excitation?

inhibition prevents the NMDA receptor from opening (will not have enough depolarization to kick out the Mg)

What does the NMDA receptor allow to flow through?

K, Na, and Ca

Activation of excitatory axon generates _____________, which closes some of the Ca channels on the __________ axon channel.

endocannabinoids; inhibitory

The endocannabinoids will shut off some of the inhibition, allowing what?

allows the NMDA receptor to be activated

How do the two types of plasticity connect?

the generation of LTP due to the cannabinoid partially shutting off inhibition at nearby synapses

1) AMPA depolarizes cell membrane, allows Ca influx

2) endocannabinoids are formed and released

3) endocannabinoids bind CB1 receptors

4) AMPA receptors provide a larger depolarization event

5) NMDA receptors open, generating LTP

What does serotonin do?

increases transmitter release which gives a stronger behavioral response (gill withdrawal)