Lecture 17: Brain Circuit mediating extinction of Pavlovian fear conditioning

What does extinction allow you to do?

Allows people to learn to detect changes in established predictive relationships and how these relationships are updated.

What is the typical paradigm in fear conditioning?

How do you know that extinction is new learning?

Relapse phenomena →
Renewal - physical context changes
Spontaneous recovery - temporal context
Reinstatement - internal cortex

What are the different types of Renewal?

There are multiple forms of renewal with the three shown on the right being the most common ones

Explain what spontaneous recovery is?

When after an extended period time, initial association memory returns and at test, they still show the fear response.

Explain what reinstatement is?

Wherein - Extinguished fear is reinstated when experiencing a stressful event between extinction and stress. Normally, the stressful event is encountering the shock US alone, but reinstatement can be observed when encountering any kind of stressful event.

What did a test of extinction of specific PIT do and show?

Rats were first pavlovian conditioned to associate S1-O1 and S2-O2, and then trained instrumentally between a R1/2 and O1/2. Pavlovian extinction was conducted on S1 only. Then looked at responses at the test depending on which cue was exposed.
Found that pavlovian extinction did not remove specific PIT. Strongly suggests that extinction is NEW cleaning. (extinction is very fragile)

What are the important brain parts for extinction of fear?

BLA and the medial prefrontal cortex and the interactions between them to learn to inhibit fear.

What did studies wherein the BLA was inhibited using muscimol find about its role in extinction?

Researchers inactivated the BLA during extinction of previously conditioned auditory stimuli. It showed that BLA inactivation during extinction suppressed freezing. Therefore, BLA is necessary for the acquisition of fear extinction.

What did wherein the BLA inhibit with the CS being context?

Following exposure to the US in a different context,, the BLA was inactivated after extinction training. During the test the following day, rats that had received BLA inactivation displayed greater freezing. Thus, the BLA is necessary for the consolidation of fear extinction.

What is common problem in examining the role of the BLA in the retrieval/expression of fear extinction?

If you disrupt BLA the animal cannot express fear (from previous lectures).
Solution → to target specific BLA neurons - red neurons which were fear neurons and blue which were extinction neurons (which were identified using electrophysiological recordings).
Researchers inactivated blue extinction neurons during freezing → finding that this increased freezing HOWEVER, inactivating before the test had no effect . This implies that BLA is not necessary for the retrieval/expression of fear extinction.

What did researchers find about extinction and fear neuron projection?

Fear neurons project to the mPFC but not back, the extinction neurons mPFC receives and sends signals from.

What did PL vs. IL inactivation found during extinction?

PL and IL were infused with muscimol or saline.
Found that the PL is necessary for the expression of conditioned fear but not the acquisition of fear extinction. The IL may be necessary for the acquisition of fear extinction.

What did studies specifically on IL activation find?

IL was inactivated during extinction training or immediately after this training using muscimol infusions. Inactivation during training had no effect, however, at test, the IL inactivated rats showed greater freezing suggesting that it is important for fear extinction. Inactivation immediately after extinction training also resulted in greater freezing at test the following day.
Given that the effects of muscimol infusions tend to take a lot time to degrade out of rat systems, the results support the inactivate mostly exerts effects after training – suggesting that the IL is crucial for consolidation but not the acquisition of fear extinction.

What did IL optical silencing find?

Using optogenetics to freeze the IL at test, implying that it is necessary for the retrieval and expression of fear extinction.

What are the theories surrounding how the IL inhibits fear?

There are two main proposals involving the IL activating

1. BLA “extinction neurons”
2. A network if inhibitory interneurons located between the BLA and the CeA. These interneurons are called intercalated cells of ITC (see yellow arrows).

Which theory about how the IL inhibit fear find support?

The intercalated cells theory,
In this study, intercalated cells were selectively lesions using D-Sap, which targeted a specific neuron present in the IL after learning. The rats with the D-sap lesions frozen more than control than others at test, suggesting that the intercalated cells are necessary for the retrieval and expression of extinction.