Learning and Memory

Question 1

Brenda Milner

Answer 1

• 105 years old
• Related to learning + memory

Question 2

H.M

Answer 2

• Severe epilepsy
• removed hippocampus to reduce/treat epilepsy
• Epilepsy starts in a localized region of the brain. So, removing this localized region to treat epilepsy. THis is still done to this day - vast improvement.
• Often these start in the medial temporal lobe (which is near the hippocampus)
• Typically remove the MTL tissue and tge hippocampus tissue in one lobe. Not too bad of deficits because they still have the other side functional.
• In H.M, they removed the medial temporal lobes on both sides. After surgery, could not form any new memories. Still had old memories, just could not make new memories.
• This region of the brain must be necessary for forming new memories - she showed she could still learn new kinds of things.

Question 3

Tracing star task

Answer 3

With practice, H.M. improved at tracing a star while looking at it in a mirror, but he never remembered practicing the task from one day to the next.
* Trace star in mirror:
- as you practice, you get better and better.
- H.M was improving . When he comes in the next day, he is still better at doing it even though he had no memory of ever doing the task.

Question 4

Key insidght of Brenda Milner

Answer 4

The key insight of Brenda Milner’s work with H.M. is that the brain has many different and anatomically distinct memory systems. Brain has multiple memory systems involved in different kinds of memory.

Question 5

The many different memory systems that we have learned so far in the course

Answer 5

• Conditioned fear involving the amydgala. The amygdala makes an association between the tone and shock (form of memory).
• Learning to make coordinated, skilled movements smoothly and effortlessly requires the cerebellum. With practice, learning slowly and progressively, will improve at a skill. Becomes unconscious.
• Habits and related stimulus-response relationship involve the basal ganglia. Gradual habit learning, with time these become automanic.
• Working memory involves the frontal lobes.
• We are now going to focus on the memory systems involving hippocampus and MTL.

Question 6

Conscious memories of facts and events in your life involve what brain regions?

Answer 6

Conscious memory of facts and events from your life requires the hippocampus and the medial temporal lobes.

Question 7

What are the two categories of long-term memory?

Answer 7

There are two categories of long-term memory, mediated by distinct neural systems
* Explicit memory – Conscious memory of facts (semantic memory) and events (episodic memory).
- HM’s defecit
- Involves Cerebellum, Basal Ganglia
- being able to consciously draw a memory up, facts, events in life, narrative of your life.

• Implicit memory – Skills, habits, classically conditioned responses
  - Happen automatically and gradually over time
  - Does not involve conscious awareness.

Question 7

What type of memory did HM have a defecit with

Answer 7

• HM had intact working memory. He could keep something in his mind but as soon as it dropped out of working memory he forgot it. He could not transfer it to LTM.
• Remember name, where from, parents name, he just could not encode new memories.
• Deficit in explicit memories.

Question 8

Explicit and implicit memories

Answer 8

Explicit and implicit memory are mediated by separate brain circuits.

Question 9

What brain regions are necessary for forming explicit memories?

Answer 9

The Hippocampus and surrounding parahippocampal gyrus (medial temporal lobe) is essential for formation of new explicit memories.
* The hippocampus is part of the medial temporal lobe system.

Question 10

Where is the hippocampus found in the medial temporal lobe?

Answer 10

The hippocampus lines the floor of the lateral ventricle in the medial temporal lobe.

Question 11

Hippocampus regions

Answer 11

The hippocampus comprises the dentate gyrus and the CA
regions. Its inputs come from the entorhinal cortex.
* The perforant pathway is the pathway that goes from the enthorhinal cortex who feeds into the hippocampus.
* Enthorinal cortex is the cortex immediately leading into the hippocampus and feeds its axons into the hippocampus.

Question 12

Explain anatomy of the regions of the hippocampus

Answer 12

• Cross-section of the hippocampus. The dentate gyrus consists of densely packed granule cells. The CA regions are comprised of pyramidal cells.
• The Dentate gyrus is one very thin layer of neurons that are densely packed with very small cells (granule cells - not the same as in the cerrebelum). These granule cells like the dentage gyrus.
• CA region has different subregions. CA1and CA3 are both pyramidal neurons forming a thin layer.

Important to remember: We do not make new neurons after we are born. One exception is the dentate gyrus which is constantly making new neurons and new neurons are being inserted into the dendate gyrus.

Question 13

Loop between Hippocampus and Cerebral cortex

IMPORTANT

Answer 13

The hippocampus forms a loop with the cerebral cortex. It gets input from and sends output to virtually every region of unimodal and multimodal association cortex.

The entorhinal cortex gets input from the different association cortex regions. Then the entorhinal cortex sends their output to the dentage gyrus (excitatory synapse). The dentate gyrus sends input to CA3 who sends input to CA1 which proceeds to send it back to the entorhinal cortex which sends it back to where it came from.

However, there is a direct pathway that goes straight from the entorhinal pathway to CA1.

Question 14

Hippocampul circuitry.

Answer 14

LTP:
* If you stimulate excititory synapses in a certain way, specific synaptic connectios can get stronger.
* The studying of this work was done in hippocampus and schaffer collateral pathway CA3 - CA1. It was all studied at CA1 synapse. However, LTP happens at all these synapses. All these synapses can change synaptic strength in response to synaptic activity and the mechanism is different at each one of these synapses.

3 reasons why people use the hippocampus to study LTP:
1) We know that Hippocampus has a lot to do with learning and memory
2) We have established that the strength of these synapses can change in response to synaptic activity.
3) Trisynaptic circuit is the same all the way down the hippocampus. So anatomically, you can slice the hippocampus anywhere and this trisynaptic circuit will be intact. It is very emmetable.

Question 15

LTP

Answer 15

Question 16

Place cells

Answer 16

• Hippocampus is important for the learning about spacial location. It plays a role in becoming familiar with the species environment.
• Hippocampal place cells are found in CA1 and CA3.
• They fire only when the animal is in a specific location.
• The population of place cells forms a map of the animal’s environment.

Experiment where they recorded electrode arrays, each electrode was from one hippocampal neurons.
- They looked at where in the box the neuron fired.
- They saw that they have place cells that fire to represent the animals location.

Did another experiment with a mouse moving along a ramp and saw that afferent neurons fire at different locations along the ramp.

Question 17

The morris water maze

Answer 17

• It is a test for spatial memory
• used to study animals spatial awareness
• white dye in the water so that the mice cannot see the platform.
• Make it find the platform, with time and practice, they become familiar with where the platform is, even if you throw it in a different locations it will make its way to the platform.

Question 18

What happens if you knock out the NMDA receptor in CA1 pyramidal cells in the Morris Water Maze test?

Answer 18

Knock-out of the NMDA receptor in CA1 pyramidal cells blocks spatial learning in mice. This NMDA receptor is important for synaptic plasticity/LTP at CA1 synapse.
* It will not get LTP at the CA1 synapse if you knock out the NMDA receptor.
* The NMDA receptor is crucial for learning about spatial environment.
* Mice with NMDA receptor knocked out, cannot learn this paradigm.

Question 19

What is the storage site for explicit memories?

Answer 19

The ultimate storage site for explicit memories is the cerebral cortex.
* Hippocampus and surrounding temporal regions are crucial for encoding long term memories and stabilizing them.
* Once the memory is consolidated/stabilized, you no loger need hippocampus.
* The hippocampus is interacting with cortex to create long-term storage.

Question 20

Role of Dopamine neurons

Answer 20

• Dopamine neurons in the substantia nigra and the ventral tegmental area project (from the substantia nigra) to the striatum and (from the VTA) to the nucleus accumbens and prefrontal cortex.
• Dopamine is involved in making certain associations and selecting certain actions that are appropriate. ie, habits
• It is involved in learning certain associations between actions/behaviors and positive outcomes.
• dopamine neurons are clustered in the brainstem
  
  • substantia nigra projects (lateral in brainstem) to putamen and caudate nucleus (parts of BG involved in movement). Neurons that degenerate in Parkinsons. Called the Nigrostriatal pathway.
  • Ventral tegmental area (medially located) projects to nucleus accumbens which is involved in behaviors associated with rewards. Anything that causes a positive effect caused release of dopamine in the nucleus accumbens nigrastriatal neurons project up to the frontal lobe (more involved in cognition and regulating behaviour).

Question 21

Experiment showing that these dopamine neurons have to do with reward

Answer 21

• James Olds and Peter Milner showed that rats will press a bar to self-stimulate ascending midbrain pathways.
• Implanted electrodes in rat brain region that stimulated ascending neuronal pathways. Ultimately, stimulation of these pathways leads to release of dopamine in the nucleus accumbens and in the frontal lobe.
• They took the stimulating electrode and hooked it up so that everytime the rat pressed a bar it would get a little electrical stimulation that would activate those neurons and release dopamine. And what they see is that the rat will press the bar forever to get that electrical stimulation. Will press the bar as long as they can - it is like an addiction (due to the dopamine released into the nucleus accumbens).
• These neurons have something to do with reward. Dopamine = pleasure

Question 22

Dopamine neurons and monkey experiment.

Answer 22

In monkeys, VTA dopamine neurons initially respond to a reward, but, with learning, they come to respond to a cue that predicts the reward. Once trained, if the reward does not follow, they reduce their firing rate.
* You start with a naïve neuron and present it with light and then give it juice (reward). After repeating this experiment, the monkey learns that there is a correlation between the light and juice.
* Once you present the light to a trained monkey, you see the excited firing rate that you would see when the juice was given to them. But after presenting the light without the juice for multiple trials, the moneky will reduce its firing rate as it is ecpecting juice but not getting it.
* Dopamine cannot simply be a pleasure molecule. It is probably doing something more complex than just signalling a reward.

Question 23

Reinforcement Learning Model

Answer 23

Reinforcement Learning Models: dopamine firing encodes a prediction-error signal, which informs other brain regions of the deviation between experience and internally represented goals.
* The dopamine is a training signal. It is telling the animal whether what is happening is better than expected.
* So, an unexpected reward leads to a burst of dopamine.
* But, once the reward is expected, then the reward itself does not elicit a burst of dopamine. Instead, it is the cue that signals the reward is coming (light) that leads to a burst of firing.
* If the animal does not get the reward, then the dopamine neuron stops firing.
* The dopamine neuron is a signal saying “something unexpected is happening”.
* Dopamine is acting a bit like the climbing fibers. A deviation from expectation.