Learning & Memory 2

Question 1

What is easier to study?

• Declarative Memory/Learning
• Procedural Memory/Learning

Answer 1

• Procedural Learning

Subjects learn to make a particular response such as a movement in response to a stimulus (these are much more easily studied in animals compared to complex experiences in declarative learning)

Question 2

What type of learning was Pavlov known for?

Answer 2

• Conditional Learning

(procedural learning)

Question 3

What types of classic conditioning did Pavlov study?

Answer 3

• Autonomic Reflexes (salivation)
• Skeletal Muscle (leg-flexion) reflexes

These reflexes were conditioned to previously neutral stimuli

Question 4

What did Skinner develop?

What type of learning was he testing for?

Answer 4

• Developed ‘Skinner’s box’
• This was used to study operant conditioning

(rat with a lever for food reward)

Question 5

What did Thorndike develop?

What type of learning was he testing for?

Answer 5

• Developed ‘puzzle boxes’
• Tested cats abilities to learn complex escape procedures

(cats in small cages with complicated latches they had to undo)

Question 6

What did Skinner conclude?

Answer 6

• Animals learn via associative mechanisms to form memory

(on a basic level - humans do not neccesarily chain up two things on a behavioural level as shown in skinner’s box)

Humans can change things in nervous system via non-associative learning

Question 7

What are the two types of procedural learning?

Answer 7

• Associative Learning
• Non-Associatie Learning

Question 8

State the two non-associative learning types?

Answer 8

1. Habituation
2. Sensitisation

Question 9

What is habitutation?

Answer 9

• Non-Associative Learning
• Gradual waning of a response with repeated presentations of a stimulus

(sitting on a seat for a long-time –> are no longer aware of the sensory information from the bottom of your seat as when first sat down)

Question 10

What is sensitisation?

Answer 10

• Non-Associative Learning
• Enhancement of responses to a stimulus after exposure to a highly arousing event

(e.g. if half asleep (habitutation to quiet sounds) but hear loud bang you start to hear the slightest sounds)

Question 11

What is associative learning?

Answer 11

• Associating one stimulus with another stimulus

Question 12

What are the two associative learning methods?

Answer 12

• Classical Conditioning
• Operant Conditioning (instrumental learning)

Question 13

What is classical conditioning?

Answer 13

• Associative Learning
• Subject learns the predictive value of one event (often behaviourally neutral) for another (usually behaviourally significant)

(e.g. ringing of bell signalling food - Pavlov) - i.e. one stimulus associated with another

Question 14

What is operant conditioning (instrumental learning)?

Answer 14

• Associative Learning
• Subject learns that their responses have behaviourally outcomes

(e. g. Thorndike’s cats manipulate a catch to escape or Skinner rat presses a lever to obtain food)
* Appropriate responses are reinforced by the behavioural outcomes

(stimulus becomes associated with a particular response)

Question 15

What rule did Donald Hebb suggest?

Answer 15

When Axon of Cell A is near enough to excite cell B or repeatedly or persistently take part in firing it, some growth process or metabolic change takes place in one or both cells so that A’s efficiency, as one of the cells firing B is increased.

(neurone A communicated with B causing it to fire –> causes the pathway between them to strengthen –> leading to associative strength change via synaptic changes –> basis for learning & memory)

Question 16

What is most likely to be the underlying mechanism of learning & memory formation?

Answer 16

• Alterations in synaptic strength

(this definitely takes place and is most likely the main underlying cause of memory & learning however it may not be - may be adjunct - non-synaptic forms of excitability changes)

Question 17

What does glutamate from a pre-synaptic terminal act on post-synaptically?

Answer 17

• Ionotropic AMPA receptors
• Ionotropic NMDA receptors
• Metabotropic Glutamate Receptors

Question 18

When are NMDA receptors activated?

Answer 18

• When post-synaptic membrane is sufficiently depolarised to overcome the Mg++ block

Question 19

In a normal state, what happens at the post-synaptic membrane of a neurone?

Answer 19

• NMDA Receptor –> blocked by Magnesium Ion (Mg++)
• AMPA Receptor –> is acted on normally by glutamate

Question 20

When is NMDA activated?

What happens?

Answer 20

• Usually blocked by Mg++
• Sufficient depolarisation (due to strong drive from AMPA) –> causes Mg++ block to come out
• Allows for Ca2+ influx through NMDA to occur
• Causing even further depolarisation of the membrane

Question 21

Brieflly, what is the NMDA receptor?

Answer 21

• Level Setter Device
• Only opens when the membrane is sufficiently depolarised by AMPA

Question 22

How is long-term potentiation (LTP) induced?

There are two ways

Answer 22

1. Strong (tetanic) activation of an afferent input –> which is sufficient to activate NMDA receptors
2. ​Weak input that coincides with post-synaptic depolarisation caused by another strong input

Question 23

What does LTP stand for?

Answer 23

• Long-Term Potentiation

Question 24

What is LTP involved in?

Answer 24

• Learning & Memory

Question 25

What occurs once a neurone/synapse has undergone **Long-Term Potentiation**?

Answer 25

* Increased number of AMPA receptors in the membrane * **Post-Synaptic Response** **increases** --\> giving a much **stronger** **post**-**synaptic** **response** (stronger EPSP) to **afferent signals** * **Increased** **firing** **likelihood** (to afferent signals) - i.e. **cells more excitable**

Question 26

Where does LTP take place?

Answer 26

* Many different brain regions (first demonstrated in hippocampus in CA1)

Question 27

What two ways related to weak inputs can cause LTP?

Answer 27

1. Weak input that **coincides** with **post-synaptic depolarisation** caused by **another strong input** 2. **Two weaker inputs** that **summate** to **depolarise** the **neuron** (each can undergo LTP) LTP can be associative

Question 28

What can lead to **Long**-**lasting** **Potentiation (LTP)**?

Answer 28

* **Brief high-frequency tetanus** (must be input specific)

Question 29

What happens in the **future** after **LTP**?

Answer 29

* **Post-synaptic neuron** would **respond** to the **input** (even if weak)

Question 30

Describe briefly the process of **associative** **learning** between the **smell** & **sight** of a **rose** using the **LTP** **mechanism**.

Answer 30

* **Sight or smell of the rose** on its own is **too** **weak** to b the **neurone** * If they **occur** **together** --\> **LTP** takes place at **both** their **synapses/inputs** * Neurone can now **recognise** the **smell** or **sight** of a **rose** (do not need to be together anymore) - **modalities** are **associated** (it will fire if either or both appear - cannnot distinguish - becomes the 'rose cell') (this is likely to occur over whole networks of neurones rather than individual ones as described)

Question 31

What is **LTP** **dependent** on?

Answer 31

* **Post-synaptic Ca2+ levels**

Question 32

How is **Ca2**+ involved in **LTP**?

Answer 32

1. **Ca2+** enters through **NMDA** **receptors** --\> **activates** **protein** **kinases (PKC)** 2. **Phosphorylate AMPA receptors** (activate them) 3. This changes **_effectiveness of existing AMPA receptors_** & contributes to **_inserting new AMPA receptors_** 4. **Post-synaptic Ca2+ levels** are **critical** & **depend** on the **exact** **level** of **NMDA** **receptor** **activation**

Question 33

What happens if **Ca2+ levels** are **not** **very** **high?**

Answer 33

* **Long-Term Depression (LTD)**

Question 34

What causes **LTD (Long Term Depression)**?

Answer 34

* Input stimulated with a **low**-**frequency** **tetanus** * **Input-specific LTD** can be measured

Question 35

Describe the process of **Long-Term Depression (LTD)**? When does it occur?

Answer 35

* Intermediate Calcium Levels (due to NMDA) * Reverse Process * **Traffics AMPA out** of the **membrane** * **Reduces** **efficacy** at the **synapse**

Question 36

Why is it important that **LTD** exists?

Answer 36

* If **LTP** was the **_only_** **synaptic** **mechanism** **available** for **learning** --\> then **neural** **networks** may **saturate** through a **lifetime** * Everything would **rack** **up** & **up** (need the ability to go up or down depending on representation) LTP & LTD work togetehr to make the changes needed in memory formation

Question 37

What does information storage in learning depend on? Where does this take place?

Answer 37

* Depend upon **LTP** & **LTD** **processes** * **Found** **widely** in the **nervous** **system** including **_hippocampus_** & **_neocortical_** **regions** (different receptor sub-types in different neurones but basic rule applies to all)

Question 38

What is important in memory formation in the cerebellum?

Answer 38

Synaptic Plasticity

Question 39

What are the two types of inputs going to purkinje cells in the cerebellar cortex?

Answer 39

1. **Climbing** **Fibre** 2. **Mossy** **Fibres** (synapse with parallel fibres of granule cells)

Question 40

Where do the inputs into the **cerebellum** come from?

Answer 40

* Climbing Fibres --\> **INFERIOR** **OLVIES** * Mossy Fibres --\> **PONTINE** **NUCLEI** (+ others)

Question 41

How does **Long-Term Depression (LTD)** occur in the **cerebellum**?

Answer 41

* Conjunctive (both) activation of **climbing** **fibre** **inputs** & **parallel** **fibre** **inputs** * Leads to **long**-**term** **depression** of _**parallel** **fibre** **synapses**_ upon **_Purkinje Fibres_**

Question 42

What does EPSP stand for?

Answer 42

* Excitatory Post-Synaptic Potentiation (EPSP)

Question 43

How is LTD stimulus specific?

Answer 43

* Recognises a **particular** **parallel** **fibre** **input** and **pairs** it with a **climbing** **fibre** **input** (causes learnign in purkinje cell)

Question 44

Describe the **molecular** **mechanism** of **Long-Term Depression (LTD)** in the **cerebellum**.

Answer 44

* Activated **parallel** **fibres** --\> causes **activation** of _**AMPA** **Receptors**_ & **_Metabotropic Glutamate Receptors_** * **Metabotropic Glutamate Receptors** --\> activates a **signalling** **pathways** through **DAG** --\> activating **PKC** (protein kinase C - calcium dependent kinase) * _**Climbing** **fibre**_ **depolarises** at the **same** **time** * High **post**-**synaptic** **calcium** **levels** are needed --\> for **PKC** --\> fulfilled by **Voltage Gated Calcium Channels** (no NMDAs in purkinje cells) * Allowing **strong** **depolarisation** * Due to **multiple** **contacts** from **climbing** **fibres** --\> many **AMPA receptors** are associated with a **single purkinje cell** --\> causing **strong calcium influx** & **PKC activation** * This causes **phosphorlation** * **AMPA receptor phosphorylation** --\> causes **crippling** in **transmission** via **AMPA** **receptors** --\> **decreasing** **AMPA** **receptor** **efficacy** (reverse role) * This causes long-term depression

Question 45

Describe the inputs from the climbing cells to the purkinje fibres.

Answer 45

* **Multipe** **contacts** from **climbing** **cells** to **purkinje** **cells** * **Climbing** **fibre** has **special** **input** of many **AMPA** **receptors** associated with **purkinje** **cell** (multiple contacts) * Opens **thousands** of **AMPA** **receptors** when **activated** --\> **causing Na+ influx** * This causes **voltage-gated channel opening** --\> causing **Ca2+ influx**

Question 46

Describe conditioned eyelid blinking experiment.

Answer 46

* **Movement** of **third** **eyelid** elicited due to **airpuff** * **Repeated** many times * **Unconditional** **stimulus** evokes an **unconditional** **response** Eventually the blink occurs without an airpuff at all (closure of eyelod os very well timed) Initially the **quiet tone conditonal stimulus (CS)** does **not** evoke a **blink** however **after** **repeats** with **unconditional stimulus** --\> **conditional** **stimulus** evokes a **conditioned** **response**

Question 47

What occurs in a large cerebellar lesion?

Answer 47

* Abolished **classical** (**pavlovian**) **conditioning** of the **eyeblink**

Question 48

Describe the molecular mechanism briefly of the airpuff & blink and how it leads to conditoined eyelid blink responses.

Answer 48

* **Climbing** **fibres** (from inferior olive) --\> fire when the **airpuff** **takes** **place** and there was **no blink (i.e. mistake)** * _**Pontine** **nuclei**_ --\> contains pathway bringing **tone** & **light** **information** --\> via **parallel** **fibres** (initially mossy fibres) --\> to the **purkinje** **cell** * These **two** **types** of **stimuli** take place at the **same** **time** at the **purkinje** fibre --\> causing **associative** **learning** *

Question 49

What is an important component of normal eyeblink conditioning and thus **cerebellum**-**dependent** **procedural** **learning**?

Answer 49

* LTD (Long-Term Depression)

Question 50

What happens in mice which have inhibition of PKC in purkinje cells?

Answer 50

* **Unable** to undergo **LTD** * Blinks are **wrongly** **timed** to the **air puff** * **Unable to learn associative nature** Mossy-parallel fibre system & climbing fibre system --\> need to work together --\> to give correct motor response --\> to give accurat e& correctly timed associatievly learned blink response (via LTD)