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Conditioning- Neurobiology, Screenshot 2024-07-04 at 12.37.55 PM,…
Conditioning- Neurobiology
Pavlovian Conditioning
Reflexive behaviour > learning about rules in our environment: some stimuli predict important events.
Learning about stimuli that predict important events is critical for successful adaptation. It allows us to use the past to predict the future, and thereby behave accordingly in the present.
Pavlovian conditioning is used to study how we learn about these predictive relationships. It demonstrates how we learn that certain stimuli in out environment predict biologically significant events.
Reflexive, rather than voluntary behaviours > the subject is a passive observer and does not need to interact with its environment.
stimuli and responses
US > unconditioned stimulus: biologically relevant stimulus that elicits an unconditioned response.
UR > unconditioned response: response that occurs naturally to the US. no learning required.
CS > conditioned stimulus: previously neutral stimulus that predicts the CS after conditioning.
CR > conditioned response: response elicited by the CS following conditioning > often the same as the US, but requires learning.
appetitive vs aversive USs
Unconditioned stimuli can be positive or negative > act as motivational systems.
The appetitive motivational system includes positive outcomes like food, drugs, or rewards.
The aversive motivational system includes negative outcomes, such as danger, pain, or frustration.
After conditioning, the CS will also come to activate the motivational system of the associated US.
CS that is pleasant activates appetitive system. CS that is negative activates aversive system.
discrete vs contextual CSs
CSs can be classified into two distinct categories; discrete and contextual.
Discrete (EVENT) CSs have a definite onset and offset. They are usually auditory or visual, and the US is typically delivered just before or after the termination of the discrete CS.
Contextual (ENVIRONMENT) CSs have no onset or offset. They typically refer to the environment where the US is delivered.
excitatory and inhibitory conditioning
Excitatory
: regular Pavlovian conditioning > learning that a stimulus predicts the arrival of an event. A positive association is formed between the CS and the US.
Inhibitory
: the CS predicts the omission of an event > negative association between the CS and the US (CS -> noUS).
The four types of conditioning are not isolated from each other, the influence and interact with each other.
Excitatory Aversive Conditioning -
Fear Conditioning
We use rodents to study fear conditioning. They are placed in a chamber and after a certain amount of time, a CS turns on.
In the case of contextual conditioning, the rat will just explore its environment without a discrete CS.
CS-US pairings are repeated a number of times, and at a later time point the rat is placed back in the chamber to test learning.
CS is presented without US. if learning occurred during conditioning, then the rat will display conditioned responses.
In context conditioning, the CR will happen as soon as the rat is back in the chamber.
The ability of the CS to elicit fear on its own implied that a fear memory (CS-US fear memory) was established.
When a rat is placed in a physical context and a discrete CS is followed by a foot shock US, fear develops to both the CS and the context. To distinguish between the two, the discrete CS can be tested in a distinct physical context, and the CS will still elicit freezing.
Measuring fear in rodents
Freezing is a species-specific behaviour exhibited by rodents when threatened, and is characterised by the absence of all movements, except those related to breathing.
Fear can also be measured by changes in heart rate, mean arterial pressure and ultrasonic vocalisations > rarely used because they are more difficult to record (surgery to implant probes).
Stages of memory formation
Typically test memory formation by giving CS-only presentations 24 hours after conditioning. Examine the distinct brain regions required for each of the stages by manipulating neural activity at each distinct stage.
If we were interested in whether a particular brain region was important for acquisition or encoding, we can temporarily inactivate neural activity via intracranial infusion of a drug immediately before conditioning.
Leaves consolidation and retrieval stages.
If there is an observable difference in behaviour during the test, we can make reasonable conclusions about that region’s involvement in the acquisition of that particular memory.
Can be done for interest in other stages
Acquisition
: occurs during the CS-US pairings at the time of conditioning and initiates encoding a memory.
Consolidation
: begins immediately after the CS-US presentation and lasts minutes to hours.
Consolidation of a memory stabilises it and establishes it into long-term memory. When testing knowledge of the CS-US association, the CS is presented on its own after the memory has been consolidated.
Retrieval/expression
: when the CS is presented, the memory of the CS-US association must be retrieved and expressed in a behavioural response.
Final stage of memory formation
Retrieval and expression are not the same. Memories can be retrieved but are not expressed in observable behaviour.
Extremely difficult to distinguish between the two when quantifying behaviour as an independent variable.
What is needed to form a fear memory?
The brain must associate the two types of information to form a CS-US memory.
Cite of the CS-US association: amygdala.
A heterogeneous structure located in the medial temporal lobe and plays an important role in processing emotional information.
In humans, rodents and other mammals, the amygdala consists of various subnuclei, including the basolateral amygdala (BLA) and the central nucleus.
Basolateral amygdala (BLA)
Consists of the lateral amygdala (LA), basal amygdala (BA) and basomedial amygdala (BM)
The brain regions that process the CS and US send projections to the BLA > widely agree that the BLA is the cite of convergence of CS and US information, allowing for the formation of the CS-US association.
The lateral amygdala is important for fear conditioning to discrete cues, as it receives projections from the visual and auditory cortices and thalamus.
The basal amygdala is critical for context fear conditioning as it receives projections from the hippocampus.
Inactivation of the BLA
Studies have demonstrated the role of the BLA in fear conditioning by temporarily inactivating it at various points of time in training and testing.
Control animals that received saline before training and test (or the saline-saline group on the far left of each graph), showed considerable fear to both the tone and the context.
The muscimol-saline group received BLA inactivation before training, but not test, showed very little fear to the tone and to the context. This indicates that the BLA is required during the acquisition of fear memories about discrete cues and contexts.
The saline-muscimol group received saline infusions before conditioning, and muscimol before test. These animals showed no fear to the tone or context, indicating that BLA is required for the retrieval/expression of the fear memory. although the BLA was functioning during fear acquisition, the BLA inactivation rendered the animals incapable of retrieving and expressing that memory
animals that received muscimol infusions before training and testing showed no fear to the tone or context.
Cellular and molecular changes
The formation of a memory requires a chain or cascade of molecular events in the neurons supporting the memory. These events produce durable physiological changes in the neurons that are believed to be the underlying substrates of the memory.
The cascade of events involved in the formation of Pavlovian fear memories in the BLA start at the time of acquisition and ends once consolidation takes place.
Activation of NMDAr (NMDA receptors)
NMDAr are a type of glutamate receptor, that when activated, excite the post-synaptic neuron, and initiate the cascade of events
blocking NMDAr before training impaired the acquisition of fear to the tone and the context: animals that were infused with either a high dose or a low dose of ifenprodil showed less fear than animals infused with vehicle
infusions of ifenprodil before the tests did not impair expression of fear to either the tone or context, as animals that were infused with both doses of the drug showed as much fear as control animals.
indicates that NMDAr activation in the BLA is required for the acquisition, but not retrieval/expression, of fear
Synthesis of new proteins
occurs during the consolidation stage. The synthesis of new proteins allows the implementation of structural and physiological changes in neurons that support a memory.
When rats were tested 24 hours later for fear to the tone, anisomycin (inhibits protein synthesis) impaired fear in a dose-dependent manner. That is, the higher the dose the stronger the impairment that was observed.
indicates that protein synthesis in the BLA is necessary for consolidation of the fear memory.
The brain must process information about the US.
The brain regions involved in processing the US depend on the nature of the US being used.
Footshock: aversive US processed by the somatosensory thalamus, and somatosensory cortex.
The brain must then retrieve this memory to coordinate the conditioned fear response.
central nucleus of the amygdala (CeA)*
lies medial to the BLA and receives many excitatory projections from the BLA. In turn, the CeA projects to many brainstem structures that mediate various components of a fear response.
CeA has mostly been viewed as the output structure (or the relay) of the amygdala that coordinates the expression of fear.
one model of Pavlovian fear conditioning is that the BLA and CeA function serially, where the CS-US association is formed and stored in the BLA. Subsequent retrieval of the memory in the BLA then activates the CeA, which coordinates fear responses through its projection to the brainstem
The brain must process information about the CS, whether it is a discrete stimulus or a context stimulus.
The brain regions involved in processing the CS depend on the modality of the CS that is being used.
Visual:
Visual thalamus
Visual cortex
Context:
HIPPOCAMPUS
A sea-horse-shaped structure located in the medial temporal lobe. Important in the formation of new memories and also plays a critical role in learning and emotions.
lesions of the hippocampus
Rats received context fear conditioning
Group 1: control sham lesion of the hippocampus before conditioning (control)
Group 2: lesion of the hippocampus before conditioning
Group 3: received control sham lesion after conditioning
Group 4: received lesion of the hippocampus after conditioning
Similar amount of fear during conditioning > lesion of hippocampus before conditioning does not prevent freezing response.
Lesion of the hippocampus after conditioning impaired context fear conditioning. G4 displayed lower amount of fear.
Impairment suggests that hippocampus is required for context fear conditioning, but if this was true the G2 should be impaired as well.
What exactly is a context?
A space composed of elemental features. By default we establish a configural representation of the context > bind all elements together to form a complex and accurate representation of what the context space includes.
Allows for pattern completion and reduces cognitive load by preventing processing of each element individually.
Hippocampus responsible for doing this ^^ but if its unavailable, each element in the context will be processed independently in various cortical regions.
Dual-Process Theory
Three central assumptions:
That a context can be processed as an independent set of features > involves cortical areas
A unique representation of a context can be formed, where all independent features are bound together > involves hippocampus
By default, the unique representation dominates and prevents processing of each single element.
Hippocampus lesioned DURING conditioning in G2, meaning no configural representation of the context can be formed. All elements are processed independently, but still associated with shock, therefore the rat displays fear.
In G4, the hippocampus was lesioned AFTER conditioning. Configural representation was formed (no processing of single elements) and was associated with shock. After lesion, the hippocampus was not able to retrieve the context representation, so no fear was displayed.
Auditory:
Auditory thalamus (fast)
Auditory cortex (slow, but more detailed)
