Synaptic Plasticity and Schizophrenia

Question 1

What are the positive symptoms of schizophrenia?

Answer 1

Lecture 17, slide 4-5

Question 2

What are the two different neurochemical theories of schizophrenia?

Answer 2

-dopamine hypothesis
-glutamate hypothesis
These theories are not mutually exclusive (they are likely to coexist).

Question 3

What is evidence is there for the dopamine hypothesis of schizophrenia?

Answer 3

Lecture 17, slide 8

Question 4

What is the saliency of a stimulus? What is abberant salience?

Answer 4

Lecture 17, slide 9-10

Question 5

What evidence is there for the glutamate hypothesis of schizophrenia?

Answer 5

Lecture 17, slide 12

Question 6

What evidence is there for a relationship between GluA1 and schizophrenia?

Answer 6

Lecture 17, slide 19

Question 7

What is the difference between spatial reference memory and spatial working memory?

Answer 7

Lecture 17, slide 31

Question 8

What is GluA1 required for? What is it not required for?

Answer 8

Lecture 17, slide 33

Question 9

What is habituation? What is short-term habituation? What is long-term habituation?

Answer 9

Lecture 17, slide 57

• Habituation (in this situation) is the decline in the tendency to pay attention to stimuli that have become familiar due to priming/prior exposure.
• Habituation can be long-term or short-term. Long-term habituation is associative (e.g. context-dependent object recognition), while short-term habituation is non-associative (e.g. recency-dependent object recognition)

Question 10

Describe the SOP model.

Answer 10

Lecture 17, slide 72, 77-83, 92-94

• There are three states:
• A1: primary active state. It has a limited capacity
• A2: secondary activity state. It has a limited capacity, but its capacity is greater than A1’s.
• I: inactive state. Elements in this state are stored in long-term memory and are no longer being processed. This state has close to infinite capacity.
• In this model, stimuli are represented as a set of elements. Elements of a stimulus can only be in one state at a time, but the different elements of a single stimulus can be in multiple states.
• When a stimulus is presented its elements transfer via route 1 (I to A). These elements then rapidly decay to A2 (via route 2), then elements eventually decay back to I (route 3)
• Elements in the different states can generate differential responses:
• elements in I cannot generate an attentional/behavioural response
• elements in A1 can generate a strong attentional/behavioural response
• elements in A2 can generate a weak attentional/behavioural response

Question 11

What is priming? What are the two different types of priming?

Answer 11

Lecture 17, slide 68-71

Priming causes habituation because it transfers element into A2. There are two types:

• Self-generated priming: presentation of stimulus causes it to enter A1. Then the elements decay to A2. This type of priming (route 2) underlies short-term habituation.
• This was demonstrated by Terry, 1976. (slide 71)
• retrieval-generated priming: during memory retrieval, the stimulus is recalled into A2 state (short-term memory) from I state (long-term memory). (route 4)
• this can be observed in the Kamin’s blocking effect. (slide 69)

Question 12

How does the SOP model explain STH?

Answer 12

Lecture 17, slide 84-87

• When a stimulus is initially presented, its elements are transferred to A1 and so initially there is a strong response (I.e. the initial presentation of elements attracts high levels of attention).
• These elements rapidly decay into A2 state. These elements have undergone self-generated priming. If the stimulus is presented again (before the elements can decay into I), then elements cannot return to A state (since there is no direct route from A2 to A1). This causes a weaker response/a reduction in the activation of A1 (since there will be a lot of elements in A2, there will be fewer elements in I state available to be activated into A1). Therefore, more recent stimuli are more likely to be habituated in this way (e.g. recency-dependent object recognition)
• this may be one possible explanation for latent inhibition.

Question 13

How does the SOP model explain LTH?

Answer 13

Lecture 17, slide 88-91

• When two stimuli are presented close together in time (close temporal proximity), their elements will be in A1 at the same time. These elements in the A1 state are able to form excitatory associations.
• If both stimuli elements are back in the I state, then presenting one stimulus (e.g.X) again will associatively activate the other stimulus (e.g.Y) elements into the A2 state (via route 4). (retrieval generated priming).
• If Y is presented while its elements are still in A2, then it will generate a response weaker than its initial response because there will be a reduction in the activation of elements into A1.
• e.g. as seen in context-dependent object-recognition (and in the context specificity of latent inhibition), where the context primes the memory of an object/stimulus into A2 state (retrieval generated priming).

Question 14

What is the behavioural phenotype of the GluA1 KO mice?

Answer 14

Lecture 17, slide 61

Question 15

How does the SOP model explain the behavioural phenotype of the GluA1 KO mice?

Answer 15

Lecture 17, slide 96-99

Question 16

Describe the studies that show the behavioural phenotype of the GluA1 KO mice?

Answer 16

Lecture 17, slide 36-60

• KOs had impaired short-term habituation:
• mice with GluA1 KOs had impaired spatial novelty vs familiarity discrimination (I.e. they had impaired spatial novelty preference) in the Novelty Preference Test. They had no novelty presence unlike controls. (Sanderson et al., 2007).
• KOs had impaired short-term habituation (and normal long-term habituation). This is shown in the object recognition task. (Sanderson et al., 2011a):
• in the object recognition task, the KOs had no preference for the novel object (unlike controls). This shows that they had impaired short-term habituation.
• in the recency variation of the task (recency-dependent object recognition): the KO mice showed no preference to explore the less recent object over the more recent object (unlike controls). This shows that they had impaired short-term habituation (STH).
• in the context-dependent object recognition task: KOs showed the same context-dependent preference for objects as the wildtype group. This task assessed long-term habituation (LTH), so the KO mice had normal LTH.
• KOs exhibited sensitization, and it was stimulus-specific. (Sanderson et al., 2011b) :
• They measured the orienting responses of rodents to lights in to study habituation.
• task: In an operant box, the rodents are presented with lights that came in pairs. In the ‘same’ trials, both lights were the same. In the ‘different’ trial, the second light was different to the first light.
• results: wildtype mice had habituated in the ‘same’ trials (had a decreased orienting response when the same light was repeated), but KO mice were sensitized (had an increased orienting response when the same light was repeated).
• KOs have impaired STH, but enhanced LTH. (Sanderson et al., 2009) :
• task: Novelty preference test. There were two group of mice. In the exposure training of one group, the exposure trials were separated by 1 minute (this condition favours STH. STH group). In the exposure training of the other group, the exposure trials were separated by 24 hours (this condition favours LTH. LTH group).
• results: the STH group had impaired STH compared to controls. The LTH group had enhanced LTH compared to controls.

Question 17

Why is Wagner’s model called Sometimes Opponent Processes?

Answer 17

Lecture 17, slide 101-102

Question 18

Is GluA1 important in AMPAR trafficking?

Answer 18

Lecture 17, slide 21-23