cellular learning & memory

Question 1

what is learning?

Answer 1

learning refers to the process by which experiences change our brain and hence our behaviour. we refer to these changes as memories. memories can be transient or durable, explicit or implicit, personal or impersonal.

Question 2

what is retrieval?

Answer 2

accessing memories

Question 3

what is neuronal plasticity?

Answer 3

the cellular basis of long-term memory is neuronal plasticity, which refers to the ability of neurons to change and adapt.

Question 4

to study neuronal plasticity, what do researchers measure?

Answer 4

1) the intrinsic excitability of neurons, which is the number of action potentials they exhibit when the cell membrane is depolarized a at amount.

2) synaptic strength - how large the postsynaptic response is when a presynaptic neuron has an action potential.

Question 5

what is synaptic plasticity?

Answer 5

a change in synaptic strength

Question 6

true or false: it is difficult to measure the intrinsic excitability of a neuron in a brain slice recording

Answer 6

false, it is easy.

Question 7

how de we measure intrinsic excitability of a neuron?

what does the intrinsic excitability relate to?

Answer 7

by injected depolarizing current into it and counting the number of action potentials.

we can repeat this measurement over-time. perhaps we wash serotonin over the neuron for a few minutes and then re-measure its excitability one hour later.

a brief exposure to serotonin made this neuron more sensitive to membrane depolarization.

this change might normally be triggered by the sensation of pain, and it could make an animal hypersensitive to touch for a few hours.

the intrinsic excitability of a neuron relates to the ion channels on its membrane. a neuron can become more excitable by expressing fewer potassium leak channels.

Question 8

true or false: we can measure synaptic plasticity in brain slice recordings.

Answer 8

true, we electrically stimulate one region and all the axons of this region have action potentials. some of those axons can synapse on the cell we’re recording from.

Question 9

what is synaptic plasticity?

Answer 9

Postsynaptic responses are usually stable over time, but certain patterns of stimulation can change the strength of the synapse in an enduring manner.

Synaptic plasticity often involves pre- and postsynaptic changes.
* On the presynaptic side, there may be changes in the number of vesicles, the amount of neurotransmitter per vesicle, and the number of vesicles that are released following an action potential.
* On the postsynaptic side, there may be changes in the number of receptors, the effects of the receptors and their sensitivity to neurotransmitter.

If you repeatedly stimulate the axon 100 times per second, the synapse tends to be stronger.

the only way we can study this is if we study subthreshold postsynaptic responses.

Question 10

what is a EPSP?

Answer 10

if the postsynaptic response is depolarization. there is glutamate release.

Question 11

what is Aplysia?

Answer 11

an invertebrate sea slug with a simple nervous system (~20,000 neurons).

it has a gill for breathing and a siphon through which it expels water and waste.

Aplysia reflexively withdraw their gill when their siphon is touched.

Repeated light touches to the siphon reduce the magnitude of the gill withdrawal reflex to the point where light touches are ignored.

this is an example of habituation.

Question 12

what is habituation?

Answer 12

a reduced physiological or behavioural response to a repeated stimulus.

Question 13

what is sensitization?

Answer 13

another type of non-associative learning, when exposure to a strong stimulus (often painful) results in heightened responses to other stimuli.

Question 14

talk about the habituation of the gill withdrawal reflex of the Aplysia.

Answer 14

The gill-withdrawal reflex habituates after repeated light touches to the siphon.

we make this test: when habituation is observed, is the sensory neuron less sensitive to touch?
no, it depolarizes the same amount.

Is the sensory neuron less excitable in general?
No, the neuron has the same number of action potentials when depolarized a set amount before & after habituation.

Is the connection between the neurons weaker?
Yes, after habituation, there is a smaller response in the motor neuron when the sensory neuron spikes.
- On the presynaptic side, we see less vesicles in the axon terminal and less are released in response to an action potential.
- On the postsynaptic side, there are no obvious changes. The number and type of glutamate receptors is unchanged.

Is the motor neuron less excitable in general?
No, it spikes the same when depolarized before/after habituation.

Is the connection between the motor neuron and the gill weaker? No, the gill responds similarly when the motor neuron has an action potential before and after habituation.

Question 15

true or false: most synapses in the mammalian brain are highly plastic; they continually change shape.

Answer 15

true

Question 16

what does changes in the synaptic strength involve?

Answer 16

pre- and postsynaptic changes; both sides of the synapse tend to grow larger or smaller in tandem.
* The presynaptic side grows to accommodate more synaptic vesicles.
* The postsynaptic side grows to accommodate more neurotransmitter receptors.
* Synapses can become so big that they split into two; the presynaptic axon will branch accordingly.
* Synapses can also shrink and completely disappear; the axon will look for another cell to synapse on.

Question 17

what is long-term potentiation (LTP)?

Answer 17

An enduring increase in the strength of the connection between two neurons (i.e., increased synaptic strength).
- We can induce LTP in a brain slice by repeatedly stimulating the inputs to a neuron at a high-frequency. This procedure involves a tetanic stimulation, typically 100 Hz stimulation for 1 second (repeated 4 times).
- LTP is often initiated on the postsynaptic side (more receptors). But the postsynaptic membrane can release retrograde signaling molecules such as nitric oxide (NO) to trigger complementary changes on the presynaptic
side (e.g., more neurotransmitter release per spike).

Question 18

what is long-term depression (LTD)?

Answer 18

An enduring decrease in the strength of the connection between two neurons (i.e., decreased synaptic strength).
- We can induce LTD in a brain slice by stimulating the inputs to a neuron at a low-frequency (one stimulation a second for 10 minutes).
- LTD is often initiated on the postsynaptic side (fewer receptors). But the postsynaptic membrane can release retrograde signaling molecules such as endocannabinoids to trigger complementary changes on the presynaptic side (e.g., less neurotransmitter release per spike).

Question 19

what does high frequency stimulation (100 Hz) of afferent glutamate inputs often produce?

Answer 19

LTP.

Question 20

High frequency stimulation (100 Hz) of afferent glutamate inputs often produces LTP. Yet the same amount of stimulation at a slower rate (1 Hz) often produces LTD. Why???

Answer 20

• LTP and LTD are a function of the number of times the synapse was activated as well as whether the postsynaptic neuron fired action potentials at those precise times.
• For LTP to occur, the release of neurotransmitter into the synapse must coincide with a substantial depolarization of the postsynaptic cell (normally associated with action potentials).
• High frequency stimulation of afferent inputs typically causes LTP (synaptic strengthening) because the postsynaptic neuron tends to spike in response to this stimulation. The depolarizing effect of each EPSP quickly adds up to bring the neuron across threshold.
• In contrast, low frequency stimulation is often insufficient to get postsynaptic neurons to spike, as there is enough time in between each stimulation for the neuron to return to its resting state.

Question 21

what are the two types of receptors in nearly every glutamate synapse?

Answer 21

AMPA and NMDA.
ionotropic receptors and permeable to Na+ when open.

Question 22

describe AMPA receptors?

Answer 22

ionotropic glutamate receptor that mediates most of the fast excitatory synaptic currents in the brain.

it lets in Na+ when bound to glutamate. They cause membrane depolarization, EPSPs.

Question 23

describe NMDA receptors

Answer 23

ionotropic glutamate receptor that mediates most of the fast excitatory synaptic currents in the brain. it is permeable to Na+ and Ca2+, but it does not consistently cause membrane depolarization. The pore of the NMDA receptor gets clogged by a magnesium ion (Mg2+) when the membrane potential is more negative than -40 mV, which is typical of a neuron at rest.

the pore is a little bigger than for AMPA receptors.
magnesium gets clogged in the pore and current can’t pass.

Mg2+ does not clog the NMDA receptor when the membrane is above -40 mV (depolarized), when neurons spike.

so for NMDA, glutamate has to activate it, but it only passes current if the cells are already depolarized a fair amount.

Question 24

what receptors determine the strength of the synapse in glutamate synapses?

Answer 24

AMPA receptors, as they always let in Na+ and depolarize the membrane when activated.

Question 25

where does the depolarization comes from in glutamate synapses?

Answer 25

activated AMPA receptors.

Question 26

what regulates the number of AMPA receptors in a synapse?

Answer 26

the activity of neighboring NMDA receptors. Ca2+ enters the postsynaptic membrane through activated NMDA receptors only when the membrane is already substantially depolarized because of other excitatory synaptic inputs. The influx of Ca2+ launches an intracellular signalling cascade that puts more AMPA receptors in the synapse.

Question 27

what is CaMKII ?

Answer 27

The type II calcium-calmodulin kinase. This enzyme gets activated by Ca2+ influx through NMDA receptors. When activated, CaMKII increases the number of AMPA glutamate receptors in the synapse, so it responsible for long term increases in synaptic strength (LTP) at glutamatergic synapses.

Question 28

what is Donald Hebb's famous hypothesis? | what is this phenomenon called?

Answer 28

The cellular basis of learning involves the strengthening of weak synaptic connections that happen to be active when the postsynaptic neuron fires an action potential. Basically, neurons that “fire together, wire together” more strongly. This phenomenon is called associative LTP (to differentiate it from tetanic LTP which was discovered first). think of air puff and tone example.

Question 29

how do you demonstrate associative LTP in the hippocampus?

Answer 29

* Simultaneous stimulation of the weak and strong pathways causes the weak pathway to become stronger. * The weak pathway can become strong enough to trigger action potentials in downstream neurons on its own. If the activity of strong synapses is sufficient to trigger an action potential in the neuron, the dendritic spike will depolarize the membrane of dendritic spines, priming NMDA receptors so that any weak synapses active at that time will become strenghtened.