Summary: A new study shows that the brain can base choices not only on direct experiences but also on indirect links between stimuli that initially seem unrelated. In experiments with mice, researchers found that a sweet taste could be rejected after it became indirectly associated with an aversive event through a shared scent.
This sophisticated form of learning depends on activity in the basolateral amygdala and its communication with other brain regions. The results clarify how incidental associations shape decision-making and suggest possible directions for treating disorders such as PTSD and psychosis.
Key facts:
- Indirect learning: Mice avoided a sweet taste after it became indirectly linked to a negative stimulus via a shared odor.
- Amygdala involvement: The basolateral amygdala was essential for forming these mediated associations; inhibiting it prevented the learning.
- Mental health relevance: Disruptions in these circuits may underlie symptoms in PTSD and psychosis, offering potential therapeutic targets.
Source: IMIM
How does the brain form decisions from indirect relationships?
Every day, our choices are guided not only by direct pairings of events but also by incidental, higher-order associations between sensory cues that were never explicitly linked to reward or punishment. A research team from the Cellular Mechanisms in Physiological and Pathological Behavior Group at the Hospital del Mar Research Institute explored how such indirect associations are encoded in the brain and which neural circuits mediate them. Their findings were published in PNAS.
Working primarily with first author José Antonio González Parra and under the supervision of Dr. Arnau Busquets, the team used behavioral paradigms in mice to isolate how the brain links stimuli across senses. Instead of directly pairing one sensory cue with a reinforcer, the protocol created chains of associations: two odors were each paired with different tastes, and later one odor was paired with an aversive event. The critical observation was that when the odor associated with sweetness was later paired with an unpleasant stimulus, mice began to avoid the sweet taste itself—demonstrating an indirect, mediated aversion.
In other words, the animals formed a higher-order association: the sweet taste acquired a negative value because it was connected to an odor that had become aversive. This sensory preconditioning-like effect reveals how incidental odor–taste links can drive future behavioral choices even without a direct taste–punishment pairing.
The basolateral amygdala and a distributed brain circuit
To map the neural substrates of these incidental associations, researchers used genetically targeted tools delivered by viral vectors to label and manipulate activated neuronal populations. They identified neuronal ensembles in the basolateral amygdala that became selectively active during odor–taste encoding. Using chemogenetic inhibition of the basolateral amygdala during the incidental association phase, the team showed a causal role for this region: when amygdala activity was suppressed, mice failed to form the mediated aversion.
Imaging and tracing experiments further revealed interactions between the amygdala and other areas, notably projections from the lateral entorhinal cortex to the basolateral amygdala. These projections were preferentially activated during odor–taste pairing, and chemogenetic disruption of this specific circuit also impaired the mediated aversion. Together, the data define a circuit in which lateral entorhinal inputs to the basolateral amygdala contribute to encoding incidental multisensory associations.
Dr. Busquets notes that the circuits identified in mice are likely to have parallels in the human brain. Because alterations in incidental associative processes are implicated in several psychiatric conditions, these findings have translational relevance: understanding how incidental odor–taste associations are encoded may inform future interventions targeting amygdala-related dysfunction.
Potential therapeutic strategies could include targeted modulation of activity in the basolateral amygdala or its afferent inputs, including noninvasive stimulation or neuromodulatory approaches, to correct maladaptive indirect associations that contribute to disorders such as PTSD or psychosis.
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. Published in PNAS.
Abstract
Projecting neurons from the lateral entorhinal cortex to the basolateral amygdala mediate the encoding of incidental odor-taste associations
From our earliest experiences, we form incidental associations between different sensory cues that influence choices and help us adapt to a changing environment. Everyday behavior is often governed by indirect associations among stimuli that have never been directly paired with a reinforcer. This higher-order conditioning can be studied in animals using sensory preconditioning protocols.
Using TRAP2 transgenic mice, the study examined which brain regions encode associations between olfactory and gustatory stimuli and support expression of an aversive odor–taste sensory preconditioning paradigm. Neuronal ensembles in the basolateral amygdala were specifically activated during odor–taste associations. Chemogenetic inhibition of the basolateral amygdala during the incidental association phase impaired the mediated responses, demonstrating a causal role.
Retrograde tracing showed that projections from the lateral entorhinal cortex to the basolateral amygdala are preferentially engaged during odor–taste encoding. Inhibiting this circuit also disrupted mediated aversion performance. Altogether, these results highlight the basolateral amygdala as a key modulator of incidental associations and reveal a brain circuit crucial for encoding complex multisensory relationships that influence decision-making.