By Dr. Tim Sandle
July 5, 2025
DIGITAL JOURNAL
Juree Burgett, who traveled from Kansas, smells various varieties of cannabis at a dispensary in Kansas City, Missouri -- a state where recreational pot use is now legal - Copyright AFP LOIC VENANCE
Does a change in smell lead our brains to switch interest from one thing to another? Certainly, our brain makes decisions based on direct associations between stimuli in our environment. Scientists have been investigating how the brain makes decisions by participating in the storage of associations between different stimuli.
Investigating rodents, researchers from the Hospital del Mar Medical Research Institute demonstrate how mice taught to link smells with tastes, and later fear, can reveal, upon analysis of the mouse brain, how the amygdala teams up with cortical regions to let the brain draw powerful indirect connections.
The relevance to humans is because the researchers believe that the brain circuits involved in decision-making processes in humans are similar to those in mice.
The researchers set out 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.
Lead scientist Dr. Arnau Busquets explains: “The project aims to understand how the brain enables us to make decisions based on indirect relationships between stimuli in our environment.”
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.
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.
By deploying imaging techniques, the researchers were next 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 Busquets.
The scientists also confirmed that if amygdala (located in the brain’s limbic system) activity was inhibited while the mice were exposed to the stimuli, the animals were unable to form these indirect associations. The main function of the amygdala is to regulate emotions, such as fear and aggression.
Amygdala dysfunction has been linked to several mental health conditions, including social anxiety, obsessive-compulsive disorder, generalized anxiety disorder, post-traumatic stress disorder (PTSD), schizophrenia, depression, and bipolar disorder.
Further studies involving disabling this circuit erased the links, hinting that similar pathways in humans could underlie disorders like PTSD and psychosis.These conditions could be tuned with future brain-modulation therapies.
As Busquets notes: “Alterations in these indirect associations form the basis of various mental disorders. Understanding the brain circuits involved in these complex cognitive processes can help us design therapeutic strategies for humans.”
The research appears in the journal Proceedings of the National Academy of Sciences, titled: “Projecting neurons from the lateral entorhinal cortex to the basolateral amygdala mediate the encoding of incidental odor–taste associations.”
Juree Burgett, who traveled from Kansas, smells various varieties of cannabis at a dispensary in Kansas City, Missouri -- a state where recreational pot use is now legal - Copyright AFP LOIC VENANCE
Does a change in smell lead our brains to switch interest from one thing to another? Certainly, our brain makes decisions based on direct associations between stimuli in our environment. Scientists have been investigating how the brain makes decisions by participating in the storage of associations between different stimuli.
Investigating rodents, researchers from the Hospital del Mar Medical Research Institute demonstrate how mice taught to link smells with tastes, and later fear, can reveal, upon analysis of the mouse brain, how the amygdala teams up with cortical regions to let the brain draw powerful indirect connections.
The relevance to humans is because the researchers believe that the brain circuits involved in decision-making processes in humans are similar to those in mice.
The researchers set out 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.
Lead scientist Dr. Arnau Busquets explains: “The project aims to understand how the brain enables us to make decisions based on indirect relationships between stimuli in our environment.”
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.
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.
By deploying imaging techniques, the researchers were next 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 Busquets.
The scientists also confirmed that if amygdala (located in the brain’s limbic system) activity was inhibited while the mice were exposed to the stimuli, the animals were unable to form these indirect associations. The main function of the amygdala is to regulate emotions, such as fear and aggression.
Amygdala dysfunction has been linked to several mental health conditions, including social anxiety, obsessive-compulsive disorder, generalized anxiety disorder, post-traumatic stress disorder (PTSD), schizophrenia, depression, and bipolar disorder.
Further studies involving disabling this circuit erased the links, hinting that similar pathways in humans could underlie disorders like PTSD and psychosis.These conditions could be tuned with future brain-modulation therapies.
As Busquets notes: “Alterations in these indirect associations form the basis of various mental disorders. Understanding the brain circuits involved in these complex cognitive processes can help us design therapeutic strategies for humans.”
The research appears in the journal Proceedings of the National Academy of Sciences, titled: “Projecting neurons from the lateral entorhinal cortex to the basolateral amygdala mediate the encoding of incidental odor–taste associations.”
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