1
Q
LO
A
- Discussing the different types of memory and the brain networks that support these.
- Discuss molecular mechanisms proposed to underpin memory.
- Discuss the experimental strategies that link plasticity and memory.
2
Q
We need to make distinctions of memory types…
A
- Memory vs Habit e.g., memory= person, habit= how to brush teeth
- Explicit vs Implicit e.g., explicit= recollect answer and say it
- Knowing that vs Knowing how
- Memory without record vs memory with record
- Declarative vs procedural
- Biological information
Structure –> Function seems to underpin the different types of memory
3
Q
Tell me about a study that gave insights into hippocampal-dependent memory
A
- Bilateral resection of the medial temporal lobe, to relieve severe epilepsy
- Profound memory impairment (scenes, words, faces)
- Learnt a hand – eye coordination skill (mirror drawing) over a period of 3 days (is all you need motor skills? As he couldn’t remember he did it a few days later)
HM= Henry Molaison (patient)
4
Q
Tell me about memory impaired patients but what some people like HM was able to do…
A
- Impaired in declarative:
- Conscious, verbal/ non-verbal idea, sound, image, sensation, odor, or word
- –> Could also learn to read mirror-reversed words
- Poor memory for the task and for the words that were read
- Perceptual skills, not just motor skills, were intact.
5
Q
Whats procedural knowledge?
A
- Skill-based
- Expressed through performance.
- Individuals have acquired a disposition to perform in a particular way
6
Q
Whats priming?
Give an example
What patients is it intact with?
A
- Distinct from declarative memory (e.g., reading a list of words and recalling what was there when can’t see anymore)
- priming—the improved ability to detect, produce, or classify an item based on a recent encounter with the same or related item
- Word priming
- Intact in patients with amnesia
- EEG – reduction in cortical activity –> could allow for faster perceptual processing (i.e., priming)
7
Q
Tell me the conscious/ unconscious memory systems
A
8
Q
Tell me the divisions of long-term memory
A
9
Q
What is declarative and non-declarative memory?
A
10
Q
Tell me about short term memory
A
11
Q
Tell me about how short term memory can become long term memory using HM as an example
A
12
Q
Tell me about the experiments with eyeblink conditioning
A
13
Q
What does the amygdala have critical role in?
A
The amygdala has a critical role in fear learning
14
Q
What about the amygdala is conserved widely across species?
A
Function and connectivity conserved widely across species.
15
Q
What is the amygdala activated by?
A
Amygdala activated by fear and strongly positive emotions
16
Q
Tell me about the amygdala and fear learning in people with amnesia
A
17
Q
What is procedural Habit memory characterised by?
A
Characterized by automatized, repetitive behavior.
18
Q
Habit memory and rats with disrupted hippocampal function…
A
Rats with disrupted hippocampal function, failed when they needed to acquire a flexible behavior but succeeded when they needed to respond repetitively.
Rats with caudate lesions showed the opposite pattern
19
Q
Tell me about the contrast seen in rats, similarity in humans between declarative memory and habit memory in memory-impaired patients with hippocampal lesions and those with Parkinsons
A
- A similar contrast between declarative memory and habit memory was shown for memory-impaired patients with hippocampal lesions and patients with nigrostriatal damage caused by Parkinson’s disease
- The neostriatum – affected in Parkinson’s disease (caudate nucleus and putamen, not the medial temporal lobe) is important for gradual feedback- guided learning that results in habit memory “gut feeling”
20
Q
What is the Caudate nucleus?
A
The caudate nucleus. Component of the basal ganglia. Brain’s reward system and functions as part of the cortico–basal ganglia–thalamic loop. Goal directed behavior (shown in above image).
21
Q
Tell me two strategies
A
22
Q
LO II
A
- Discussing the different types of memory and the brain networks that support these
- Discuss molecular mechanisms proposed to underpin memory
- Discuss the experimental strategies that link plasticity to memory
23
Q
“Neurons that fire together wire together”
A
24
Q
What is the neurotransmitter between synapses?
A
25
Complexity of input pathways
26
Experiment example...(1)
27
Experiment example (2)
28
Why are NMDA receptor voltage-dependent?
29
Tell me about AMPA and NMDA components?
30
Response greater with AMPA receptors?
31
Synaptic plasticity
32
Tell me about CA3 synapses (MOSSY FIBRES)
* What is required for AP
* dependent on
* what the mechanism may allow
* **Pronounced short term plasticity** (facilitation) in these synapses. (2nd potential could happen relatively quickly after first due to presence of large amounts of Ca2+)
* **Unitary EPSPs not sufficient to initiate a spike in CA3 neurons under control conditions**, but reliably cause action potentials if stimuli delivered in “bursts” Presynaptic short-term plasticity
* **Plasticity**- dependent detonation may be critical for efficient coding, storage, and recall of information in the granule cell–CA3 cell network.
* “Full detonator mode” for tens of seconds after high frequency stimulation
* With longer bursts (100 stimuli in 1 second) plasticity can be extended for tens of seconds to allow “full detonator mode” for tens of seconds after high frequency stimulation.
* **Depended on Ca2+ / calmodulin.**
* This mechanism may allow a single highly specific cue to trigger the encoding, storage, or recall of complex information in CA3 pyramidal neurons.
33
CA3 synapses
34
Hippocampal circuits
* Memory encoding of declarative memory
* Navigation
35
Tell me about the coincidence detectors **NMDARs**
* They only open when:
* There is glutamate release and postsynaptic depolarization (i.e., they are voltage dependent)
* NMDAR need to be at -40mV to be unblocked
36
**LO Lecture IV**
* **Discussing the different types of memory and the brain networks that support these.**
* **Discuss molecular mechanisms proposed to underpin memory.**
* **Discuss the experimental strategies that link plasticity and memory.**
37
Whats a memory trace and why is it studied?
A memory trace, also know as an **engram**, is a theoretical means by which memories are physically stored in the brain. The actual method of storage of memory, whether by biophysical or biochemical means, is still being debated.
There are multiple levels of analysis to understand memory storage
38
What is synaptic plasticity?
Plasticity in synapses: the ability of a synapse to strengthen or weaken over time in response to increase or decrease their activity
39
Tell me about short and long term sensitisation in synapses and what they're due to
* **Short-term sensitization** is due to an acute, PKA-dependent enhancement of glutamate release from the presynaptic terminals of sensory neurons
* **Long-term sensitization** is due to changes in gene expression, causing expression of proteins that change PKA activity and lead to changes in synapse growth
40
What is an engram?
(“memory trace”): The neural substrate responsible for storing and recalling memories.
41
Tell me some characteristics of engram cells
**Engram cells are:**
1) Activated by a learning experience,
2) Physically or chemically changed by the learning experience, and
3) Reactivated by subsequent presentation of the stimuli present at the learning experience
42
Is an engram a memory, how are they linked?
* An engram is not yet a memory but provides the necessary physical conditions for a memory to emerge.
* A memory emerges when appropriate retrieval cues reactivate an engram
43
Tell me about Morris water maze memory experiment with mice
* https://www.youtube.com/watch?v=Ak7eyPGL03I&t=174s
* Put mice/rat in water to find platform and once on platform, they sit for 20 seconds roughly and then they keep doing to see how their memory changes with increased attempts. Then change scenario to see how they behave and how it changes
* Contextual fear conditioning.
* Activation of widely distributed neuronal ensembles in the dentate gyrus, cortex and lateral amygdala (LA).
* These active neurons can be tagged! (Engram?)
44
The evolution of lesion techniques in the search for the engram
45
Tell me about another experiment done on mice/rats in order to investigate memory and memory storage
* Contextual fear conditioning. (fear that a foot shock will come which is a measure of its memory)
* Activation of widely distributed neuronal ensembles in the dentate gyrus, cortex and lateral amygdala (LA).
* These active neurons can be tagged! (Engram?)
* CREB viral vector used to make neurons more likely to be part of the engram.
* The same vector allowed toxin-mediated destruction of neurons.
* Mice with ablated neurons could still acquire fear learning task.
* Ablating a similar number of random neurons did not disrupt memory retrieval
46
Experiments for loss/gain of function
47
Fear conditioning and memory experiment
48
Whats an emerging concept about a given memory?
An emerging concept is that a given memory is stored in functionally connected multiple engram cell ensembles dispersed in multiple brain regions, each ensemble providing a unique component of the overall memory
49
Many questions remain about memory and engrams...
* How do engrams change over time?
* How does engram structure impact memory quality, strength and precision?
* What is the role of silent engrams? (engrams can be artificially activated in an Alzheimer’s Disease mouse model)
50
Whats the major challenge faced when working with engrams to understand memory?
To translate these rodent engram findings to humans with memory or information-processing deficits
51
What are the two types of long term memory and their subdivisions?
52
Tell me the areas of the brain associated with the following areas...
1. Episodic memory
2. Procedural memory, classical conditioning and semantic memory
3. familarity and priming
53
Cracking the mneminic code...
54
What does early phases of alzheimers diesease affect?
55
**Summary lecture IV**
* **Can you now or after revision?**
* **Discuss the different types of memory and the brain networks that support these.**
* **Discuss some molecular mechanisms proposed to underpin memory.**
* **Discuss the experimental strategies that are helping to link plasticity and memory.**
