How the Brain Forms Indirect Associations to Guide Complex Decisions

Summary: A new study reveals how the brain can make decisions based not only on direct experiences, but also on indirect associations between seemingly unrelated stimuli. In experiments with mice, researchers showed that a sweet taste could be rejected after it was indirectly linked to an aversive event through a shared scent.

This complex form of learning was found to rely on activity in the amygdala and its interaction with other brain regions. The findings shed light on how indirect associations shape decision-making and may offer insights into treating disorders like PTSD and psychosis.

Key Facts:

  • Indirect Learning: Mice avoided a sweet taste after it became indirectly linked to a negative stimulus through smell.
  • Amygdala’s Role: The amygdala was essential for forming these associations; when inhibited, the learning failed.
  • Mental Health Implications: Disruptions in this mechanism may underlie conditions like PTSD, offering targets for therapy.

Source: IMIM

Our brain makes decisions based on direct associations between stimuli in our environment, but it often also does so based on events that initially appear unrelated. How does it achieve this?

A recent study by the Cellular Mechanisms in Physiological and Pathological Behavior Research Group at the Hospital del Mar Research Institute, published in PNAS, offers new insights into this process and identifies the brain areas involved.

At the same time, they identified other brain areas that were also involved and interacted with the amygdala. Credit: Neuroscience News

Using observations in mice, led primarily by first author and PhD student José Antonio González Parra and supervised by Dr. Arnau Busquets, the research team was able to determine the mechanisms involved in how the brain makes decisions based on indirect associations between different stimuli.

That is, instead of directly associating a specific stimulus with a rewarding or aversive situation, the brain establishes connections between two or more stimuli.

As Dr. Busquets explains, “The project aims to understand how the brain enables us to make decisions based on indirect relationships between stimuli in our environment”.

In this context, the mice were subjected to various behavioral tests. They were trained to associate one smell-banana-with a sweet taste, and another smell-almond-with a salty taste.

Later, a negative stimulus was associated with the smell of banana. From that point on, the mice rejected the sweet taste, which was linked to the banana smell and thus carried a negative connotation.

In other words, “they formed an indirect association between the sweet taste and the aversive stimulus through its link to a specific smell”, explains Busquets.

The Role of the Amygdala

Using genetic techniques delivered via viral vectors, the researchers were able to observe which areas of the mice’s brains were activated throughout the process of encoding and consolidating the associations.

They found that the amygdala, a brain region associated with responses such as fear and anxiety and involved in certain mental disorders like psychosis and PTSD, was activated when the mice linked olfactory and taste stimuli.

At the same time, they identified other brain areas that were also involved and interacted with the amygdala. Thanks to imaging techniques, they were able to establish a connection between these areas and a part of the cerebral cortex.

“We have identified a brain circuit that controls associations between stimuli and allows for these indirect associations”, says Dr. Busquets.

They also confirmed that if amygdala activity was inhibited while the mice were exposed to the stimuli, the animals were unable to form these indirect associations.

As Dr. Arnau Busquets explains, the researchers believe that the brain circuits involved in decision-making processes in humans are similar to those in mice. Therefore, the data obtained in this newly published study could be relevant for treating certain mental disorders linked to amygdala activity.

“Alterations in these indirect associations form the basis of various mental disorders”, he adds.

“Understanding the brain circuits involved in these complex cognitive processes can help us design therapeutic strategies for humans”.

In this sense, future approaches could include brain stimulation or modulation of activity in these areas in people with PTSD or psychotic symptoms.

About this neuroscience and decision-making research news

Author: Marta Calsina
Source: IMIM
Contact: Marta Calsina – IMIM
Image: The image is credited to Neuroscience News

Original Research: Open access.
Projecting neurons from the lateral entorhinal cortex to the basolateral amygdala mediate the encoding of incidental odor-taste associations” by Arnau Busquets et al. PNAS


Abstract

Projecting neurons from the lateral entorhinal cortex to the basolateral amygdala mediate the encoding of incidental odor-taste associations

Since our first steps in life, we are forming incidental associations between diverse stimuli across various sensory modalities that influence our future choices and facilitate adaptation to environmental fluctuations.

Daily behavior is usually governed by indirect incidental associations among sensory cues that have never been explicitly paired with a reinforcer.

This phenomenon, known as higher-order conditioning, can be systematically investigated in laboratory animals through specific behavioral paradigms such as sensory preconditioning protocols.

In this study, using “Targeted Recombination in Active Populations” (TRAP2) transgenic mice, we have interrogated which are the brain areas orchestrating the encoding of associations between olfactory and gustatory stimuli and the expression of an aversive odor–taste sensory preconditioning paradigm.

We identified neuronal ensembles within the basolateral amygdala specifically activated during odor–taste associations.

To demonstrate the causal involvement of this brain region in our sensory preconditioning task, we inhibited it during the preconditioning phase (i.e., incidental associations) using a chemogenetic approach, which caused a clear impairment of the mediated responses.

In addition, using retrograde tracers in the basolateral amygdala of TRAP2 mice, we observed that the projections from the lateral entorhinal cortex to the basolateral amygdala are particularly activated during odor–taste associations.

Notably, the chemogenetic inhibition of this brain circuit impaired the mediated aversion performance in our sensory preconditioning task.

Overall, these findings highlight the amygdala as a pivotal modulator of incidental associations during an aversive sensory preconditioning task and point toward a brain circuit crucially involved in these complex cognitive processes.