Memory Mechanisms Flashcards
Inferotemporal cortex (area IT)
- Fires when presented with faces
- Different neurons are selective for different faces
- Neurons can change response to faces after multiple presentations and acquire stimulus selectivity
Distributed memory
- Memory occurs as a result of synaptic modification i.e. changes in synaptic strength → changes in response
- Distributed memory: Representation of a single memory is not stored in single neuron but in population of neurons
Example of memory being distributed
- Example: The brain interprets medium activity in Neurons A and C and high activity in Neuron B as the stimulus “Barry”
- Graceful degradation: Distributed memory ensures that a single neuron dying doesn’t mean that an entire encoded memory disappears (not one single neuron encodes for “Mark,” memory representations blend together and get confused for each other as neurons are removed instead of a catastrophic loss of memory)
Graceful degeneration
Graceful degradation: Distributed memory ensures that a single neuron dying doesn’t mean that an entire encoded memory disappears (not one single neuron encodes for “Mark,” memory representations blend together and get confused for each other as neurons are removed instead of a catastrophic loss of memory)
Which of the following are true about memory?
a) Memory is distributed in different populations of
neurons
b) Graceful degradation ensures that catastrophic loss
of memory doesn’t occur as a result of the loss of
one or some neurons
c) LTP is known as the growth of individual neurons
(neurogenesis) as a result of learning and memory
d) None of the above
e) More than one of the above
f) All of the above
Answer: E
LTP strengthens synaptic connections
What is LTP?
- LTP is a long-lasting enhancement of the effectiveness of synaptic transmission (can be measured as elevated EPSP compared to measurements in a “baseline period”)
- Induced experimentally by tetanus (brief burst of high-frequency stimulation)
- Brief tetanus (less than a minute) can lead to very prolonged LTP (still lasted after a year)
Two characteristics of LTP
- Specificity
- Associativity
LTP: Specificity
Individual synapses are strengthened via LTP, not all synapses onto a given neuron
LTP: Associativity
Nearby synapses that are weakly stimulated can also undergo LTP due to nearby synapse activation; TIMING matters
Peter the tiny horse decides to activate a bunch of neurons in your hippocampus as you see an image of spongebob. He does it so consistently (and so rapidly) that everytime you see an image of spongebob, that group of neurons gets activated. What principle(s) is this phenomenon representing?
a) Input selectivity
b) Spatial summation
c) Temporal Summation
d) Cooperativity
e) More than one of the above
f) All of the above
Answer: F
Glutamate receptors
- AMPA receptor
- NMDA receptor
AMPA receptor
- Ionotropic glutamate receptor (postsynaptic at Schaffer collateral-CA1 synapse)
- Conducts only Na+ ions
- Only requires glutamate binding for conducting ions
Glutamate receptors diagram
NMDA receptor
- Ionotropic glutamate receptor (postsynaptic at Schaffer collateral-CA1 synapse)
- Conducts Na+ and Ca++ ions
- 2 requirements for conducting ions:
1) glutamate binding
2) Postsynaptic membrane must be depolarized enough to displace Mg++ ions clogging opening to channel
What are the two requirements for conducting ions in NMDA receptor?
1.Glutamate binding
2.Postsynaptic membrane must be depolarized enough to displace Mg++ ions clogging opening to channel
Why is the NMDA receptor called a coincidence detector?
Because it signals when the presynaptic and postsynaptic elements are active at the same time
Which type of receptor only conducts Na+ ions?
AMPA receptor
Which type of receptor conducts Na+ and Ca++ ions?
NMDA receptor
Why are NMDA receptors important?
Coincidence Detector!!
➢ Requires both pre and postsynaptic activation for current to flow through them
➢ Calcium passes through them (Ca2+ is important)
- Strong activation of NMDA receptors => triggers LTP Strong NMDA activation triggers modifications of AMPAR:
- Calcium influx acts on protein kinase to:
1. Add phosphate groups to AMPA and make them more conductive
2. Increase AMPA receptors in the synapse
What are the effects of calcium influx on protein kinase?
They cause protein kinase to:
- Add phosphate groups to AMPA and make them more conductive
- Increase AMPA receptors in the synapse
Peter the tiny horse decides to do some more experiments in your brain. He decides to “spill” a bunch of inhibitor for a specific type of glutamate receptor but forgets the label. Assuming Peter has the amazing ability to see even the smallest of changes in neurons, which of the following factors will tell him which specific receptor he’s inhibiting? What would be the result?
a) Na+ concentration
b) Ca++ concentration
c) Mg + ions
d) Protein content in the cell
e) NMDA concentration
f) More than one of the above
g) All of the above
Answer: F; think coincidence detectors
Synaptic plasticity is ___
Bidirectional
Long-term potentiation
- High-frequency stimulation
- AMPA receptors phosphorylated, more delivered to the membrane
- Large calcium surge
Long-term depression
- Low-frequency stimulation
- AMPA receptors dephosphorylated, endocytosis from membrane
- Less calcium surge
BCM Theory
● Discovered by Bienenstock, Cooper, and Munro (3 faculty members or alums of Brown)
● Accounts for fact that synaptic strength can change bidirectionally
● Synapses undergo synaptic weakening when they are active (ex.
stimulated) at the same time that the postsynaptic neuron is weakly
depolarized → the end result is long-term depression (LTD)
● Experimental evidence: Low-frequency tetanic stimulation (1-5 Hz) causing
only weak depolarization of postsynaptic neuron → stimulated synapses get
weaker
● 2 scenarios
○ Synaptic transmission occurring at the same time as strong depolarization of the postsynaptic
neuron → LTP of the active synapses
○ Synaptic transmission occurring at the same time as weak or modest depolarization of the
postsynaptic neuron → LTD of the active synapses
BCM Theory - 2 scenarios
○ Synaptic transmission occurring at the same time as strong depolarization of the postsynaptic
neuron → LTP of the active synapses
○ Synaptic transmission occurring at the same time as weak or modest depolarization of the
postsynaptic neuron → LTD of the active synapses
Which of the following statements about BCM theory is true? Select all that apply:
a) BCM theory explains synaptic plasticity as a bidirectional process, allowing both strengthening (LTP) and weakening (LTD) of synapses.
b) Synaptic weakening occurs when synapses are active at the same time that the postsynaptic neuron is strongly depolarized.
c) Synaptic changes described by BCM theory are input-specific and depend on the activity of individual synapses.
d) BCM theory suggests that a threshold level of postsynaptic activity determines whether synapses undergo LTP or LTD.
e) BCM theory posits that synaptic plasticity is driven entirely by presynaptic mechanisms,
Correct: a, c, d
Mechanism of LTD
● As we saw in previous slide, weak NMDA receptor activation causes LTD → by extension, low Ca++ entry causes LTD
● Low/modest prolonged Ca++ activates protein phosphatases (instead of kinases activated by LTP)
● 2 effects
○ AMPA receptors are dephosphorylated
○ Internalization of AMPA receptors at the synapse → associated with spine shrinkage
Importantly, LTD still requires NMDA activation (just a low level instead of a high one).
LTD diagram
Activation of NMDA receptors
- Activation of NMDA receptor (which correlates to frequency of tetanic stimulation) also impacts changes in synaptic strength
- Weak NMDA activation –> LTD
- Strong NMDA activation –> LTP
Weak NMDA activation –> ___
LTD
Strong NMDA activation –> ___
LTP
What process do long-term memories require, and how does this compare to short-term memories?
- Long-term memories require new protein synthesis
- Short-term LTP/LTD do not require new protein synthesis
Evidence for the fact that long-term memories require new protein synthesis
Set up: Rat in box with two chambers, one light and one dark
- Rats naturally prefer dark –> they go to dark side
- On dark side, get shocked
- Rat no longer prefers the dark side, stays in the light –> new memory formed
- Strength of memory is quantified with amount of latency
What happens if protein synthesis is inhibited?
What factor does the durability of LTP depend on?
Protein synthesis
Explain how durability of LTP depends on protein synthesis
- LTP changes synapse but new proteins are required to convert the temporary change into a more permanent one
- Stimulation that is weak but still high enough to trigger LTP –> only a small number of synapses activates and this decays back to baseline in a few hours b/c could not trigger protein synthesis
- Stronger stimulation –> more synapses activated and long-lasting LTP b/c new protein synthesis stimulated
What happens to LTP with weaker input?
LTP eventually decays (forgettable)
What happens to LTP with stronger input?
Protein synthesis occurs, maintains LTP (memorable)
Synaptic tagging and capture
- If synaptic input A gets weak stimulation and synaptic input B gets strong stimulation at around the same time, a wave of protein synthesis caused by input B’s stimulation can also input A to consolidate its own LTP
- Input A got a tag from weak stimulation that allowed it to capture newly synthesized proteins (created by input B) and consolidate its own LTP)
- May be what allows you to remember a trivial event (weak input A) close to a momentous one (strong input B) e.g. what ou were doing during 9/11
What does synaptic tagging and capture demonstrate about memory consolidation?
a) Synaptic input with strong stimulation can create proteins that nearby weakly stimulated inputs use to consolidate their own LTP.
b) Synaptic tagging ensures that only strongly stimulated inputs consolidate their LTP.
c) Weak stimulation alone is sufficient to consolidate LTP without the need for protein synthesis.
d) Strong and weak inputs are processed independently during memory consolidation.
Answer: A
Reconsolidation means that memories are
a) stored anew when they are recalled
b) consolidated in the hippocampus and again when they are stored in neocortex
c) consolidated at multiple brain locations
d) repeatedly refreshed by a constant consolidation
a) stored anew when they are recalled
Long-term depression
a) involves the addition of NMDA receptors to the postsynaptic membrane
b) requires hyperpolarization of the postsynaptic membrane
c) occurs when memories are forgotten but not when they are remembered
d) involves increased activity in protein phosphatases
d) involves increased activity in protein phosphatases
In a passive avoidance experiment, a rat receives a foot shock when it enters the dark side of a container. An important result learned from these experiments is that
a) a food shock can erase a declarative memory but not a procedural memory
b) LTP occurs in the hippocampus when a rat learns the association between darkness and foot shock
c) stress interferes with LTP
d) for avoidance to occur, the electrical shock must be delivered at a rate that would cause LTP
b) LTP occurs in the hippocampus when a rat learns the association between darkness and foot shock
Distributed memory means that a memory is stored
a) as redundant copies in multiple brain areas
b) across multiple neurons that each respond selectively to an individual memory
c) in the pattern of synaptic connections between many neurons
d) in pieces such that individual neurons represent portions of memory, such as the features of a
face
c) in the pattern of synaptic connections between many neurons
LTD
a) Has similar requirements as LTP, except the magnitude is smaller
b) Is the mechanism by which we forget, or lose memories
c) Involves adding GABA receptors to the postsynaptic membrane
a) Has similar requirements as LTP, except the magnitude is smaller
All of the following are required to elicit NMDA-dependent LTP at synapses EXCEPT
a) depolarization of the postsynaptic cell
b) glutamate binding to NMDA receptors in the postsynaptic cell
c) Increase in calcium in the postsynaptic cell
d) Increase in the release of neurotransmitter from the presynaptic cell
d) Increase in the release of neurotransmitter from the presynaptic cell
The following would enhance LTP: activation of protein phosphatases/kinases in the pre/postsynaptic cell
Kinases in postsynaptic cell
Presenting this novel image of a face to your grandfather repeatedly would cause
a) some neurons in his IT cortex to fire less with repeated presentations
b) some neurons in his IT cortex to fire more with repeated presentations
c) LTP in his cortex
d) LTD in his cortex
e) all of the above
e) all of the above
a) Some neurons in his IT cortex to fire less with repeated presentations
This is consistent with neuronal adaptation, where some neurons decrease their firing rate after repeated exposure to the same stimulus. This is a mechanism to conserve energy and focus resources on novel stimuli.
b) Some neurons in his IT cortex to fire more with repeated presentations
Certain neurons might increase their firing rate due to sensitization or familiarity-based learning, as the repeated image could become behaviorally or emotionally relevant, leading to enhanced neural response.
