Lecture 14: Brain Circuits involved in Aversive-Conditioning

What to know about techniques and the expansion of new understanding?

Although there has been a significant expansion of new technologies in neuroscience in the last 20 years, these expansions have tended to lead to the confirmation of old theories rather than development of new theories.

What to note about Pavlovian conditioning?

The idea that it is expressed via reflexive behaviour, suggesting that the organism does not interact with these actions and this happens automatically.

Why is ‘pavlovian conditioning two-dimensional’ ?

There are two different characteristics that come to define the types of pavlovian conditioning, whether it is excitatory or inhibitory or if it is appetitive or aversive.

Describe the categories of pavlovian conditioning?

Appetitive Excitatory → a stimuli that predicts the arrival of food
Appetitive inhibitory → a stimuli that predicts the omission of food
Aversive excitatory → a stimuli that predicts the arrival of shock
Aversive inhibitory → a stimuli that predicts the omission of shock.

Explain a typical pavlovian fear conditioning paradigm?

A rat is normally first conditioned to associate light and shock with a particular environment.
Tame elapses before, at test, the rat is exposed again with the CSs to test the conditioned response of freezing.

What are the three stages of fear memory and how do you test each of the stages?

Acquisition, wherein the brain manipulation occurs before before fear conditioning

Consolidation: wherein the brain manipulation occurs just after fear conditioning

Retrieval:  wherein the brain manipulation occurs just before test.

What does the brian need to do to produce a fear (CS-US) memory?

It needs to process information about the CS, whether it is discrete or contextual.
It needs to process information about the service US
And it needs to combine both CS and US information to create an association.

Describe the difference between a discrete vs. contextual conditioned stimuli?

Discrete – refers to something like a light or tone, wherein there is an onset and an offset, compared to context – which literally means the surroundings of the animal when they are exposed to US.

What are the brain regions involved with different types of modalities?

Auditory - auditory thalamus or cortex
Visual - visual thalamus or cortex
Context CS - the hippocampus

Explain what initial examination of the relationship between the hippocampus and contextual CS found?

In a study wherein either before or after conditioning, a lesion was given to the hippocampus, researchers found an impact at test due to lesions only in the rats whose lesions were only damaged after conditioning. This paradoxically suggests that the hippocampus is involved and not involved in the learning of fear memory.

How does the dual-process model resolve the paradox in links between the hippocampus and context?

According to the dual process model, there are two ways in which information about context and it’s cues can be processed either
As an independent set of elemental features in relevant cortical areas.
As a configural representation in the hippocampus.
In the theory the configural representation is favoured as it is more cognitively efficient.
This theory explained previous results, those with the lesions the hippocampus before the conditioning had the memory processed as individual elements, and those with the lesions after conditioning, lose the memory because the brain had already processed it as a configural representation rather than individual elements.

Where is the US processed?

In the somatosensory thalamus.

Where is the US and CS association processed?

In the amygdala - which is an heterogeneous structure located in the medial temperature lobe.
More specifically as part of the lateral amygdala, the basal amygdala and the basomedial.

What is the difference between the lateral and basal amygdala?

The lateral amygdala is associated with fear conditioning to discrete cues, as it receives projections from the visual and auditory cortices and thalamus.
The basal amygdala is associated with context fear conditioning as it receives projects from the hippocampus

What did temporary basal amygdala inactivation do?

Researcher inactivated the basal amygdala either before conditioning rats with a tone and shock, or before test. They used muscimol which is a GABAa receptor that produces inhibition of neural activity. They found that activation of BLA is required for both the acquisition and retrieval/expression of fear memories as all groups that were exposed to muscimol did show a reduction of fear responding in comparison to control groups.

What did the inactivation of NMDAr in the basal amygdala do?

NMDA is an important component of the cascade causing long term learning, therefore scientists wished to discover if a suppression of NMDA would lead to less learning in the BLA.
In the study, rats were injected with Ifenprodil which is a selective antagonist of NMDAr either before conditioning or before testing. They found that those injected with the NMDAr before conditioning impaired the acquisition of fear of the tone and context.
Therefore, they found that NMDAr activation in the BLA is required for the acquisition, but not retrieval/expression, of fear memories.

What did changes to the protein synthesis inside the BLA do to fear memories?

Protein synthesis is important for the consolidation of memories, in an experiment where anisomycin ( a protein synthesis inhibitor) was injected following conditioning. They found that the higher the does of Anisomycin, the less fear conditioning was observed, indicating that protein synthesis in the BLA is necessary for consolidation of the fear memory.

What is a memory engram?

An engram refers to the physical and biochemical changes in the brain that represent the storage of a specific memory
This is a very popular theory that has only been testable in that last 15 years due to the development of genetic tools

What is a nerve ensemble?

A particular learning event will activate a specific population of neurons, or neuronal ensemble, that will undergo enduring physiological changes. These changes allow memory formation and storage. Retrieval of the memory involves reactivation of the specific neuronal ensemble.

How do new techniques allow for the testing of neuronal ensembles?

New techniques allow scientists to tag specific neurons which are activated during conditioning, these are tags durable meaning that throughout new retrieval and recall we can see if it is the same neuronal ensembles activating.

Explain fear engrams in the BLA

Using the tagging technology, we can conclude the role of the basal vs. the lateral amygdala. Basal amygdala neurons active during fear conditioning were more likely to be active when testing contextual fear. Lateral amygdala neurons active during fear conditioning were more likely to be active when testing discrete fear.

What did research suggest about the central amygdala and how does it contradict previous theories?

Recent research in which the CeA was inactivated using muscimol, finds that it was important in both the acquisition and retrieval/expression of fear memory.
This contradicts with the previous theory of serial models in which CeA is a relay under the control of the BLA and its role was only to ensure fear expression.

What do human studies say about fear conditioning and the role of the amygdala?

Case study of SM, who had bilateral amygdala lesions but an intact hippocampi

as suggested by research they could not learn to fear auditory or visual stimuli but could process factual information normally.
fMRI studies link pav fear conditioning with amygdala activity
Patients with anxiety disorders show excessive and irrational fears, agreeing with animal studies as imaging shows hyperactivity of the amygdala.
Anxiolytic drugs have been found to reduce amygdala activity

Quick summary

Context CS —> hippocampus; Discrete CS and aversive US —→ thalamus & cortex

The BLA is involved in the acquisition, consolidation and retrieval/expression of fear memories

Evidence for fear engrams in the BLA CeA contributes to acquisition and retrieval/expression of fear memories

Fear memories are durably stored in the amygdala