Summary: A new study reveals how rats can learn to fear through inference, offering insights into the neural basis of higher-order emotions. By pairing a neutral sound and image, then associating the image with an unpleasant experience, researchers showed that rats later feared the sound alone—demonstrating inferred emotional learning.
The medial prefrontal cortex (mPFC) played a key role in this process by tagging neurons during sensory pairing and activating them during emotional learning. Blocking mPFC activity disrupted this inference, while direct memory associations remained intact.
Key Facts:
- Higher-Order Emotion: Rats can infer fear from indirect associations, not just direct experiences.
- mPFC Role: The medial prefrontal cortex enables inference by linking neutral stimuli to aversive outcomes.
- Clinical Implications: Findings may help unravel mechanisms behind human anxiety and trauma-related disorders.
Source: RIKEN
Xiaowei Gu and Joshua Johansen at the RIKEN Center for Brain Science in Japan have discovered key circuitry in the rat brain that allows the learning of inferred emotions.
The study reveals how the frontal part of the brain coordinates with the amygdala—a brain region important for simple forms of emotional learning—to make this higher-order emotional ability possible.
Published in the scientific journal Nature on May 14, this breakthrough study is the first to show how the brain codes human-like internal models of emotion.
What are inferred emotions?
Consider a child who often watches a wasp fly in and out of its nest in the woods near her house. One day the child is stung by the wasp for the first time, a frightening experience that changes her emotional response to this creature but also to the nest itself. Afterward, seeing the wasp’s nest alone makes the child feel anxious and become alert and cautious.
In this scenario, the child has built an internal model that links the negative experience with the visual representation of the nest – even though the nest was not there at the time of the fearful event.
Johansen and Gu were interested in understanding the neural mechanisms that allow this type of higher-order emotional processing through inference.
To do so, they created a similar situation in animals; rats learned a neutral association between a noise and an image, then later experienced unpleasantness while seeing the image—a process called aversive conditioning.
The next day, they were tested to see if they could infer from hearing the noise alone that something unpleasant might happen. Under these conditions, rats did indeed freeze when they heard the noise, indicating their fear and showing that they too can learn inferred emotions.
Once they had a successful animal model, the researchers used a combination of calcium imaging and optogenetics to examine changes in neuron activity within a part of the brain called the medial prefrontal cortex (mPFC). As hypothesized, experiments indicated that the mPFC is the basis of emotional inference.
Before undergoing aversive conditioning, neurons in the mPFC responded similarly to both the image and the noise, whether the stimuli had been paired or not.
But after aversive learning, calcium imaging showed that the number of noise-responsive and noise/image co-responsive neurons went way up— provided the noise and image had been initially paired together when presented to the animals.
Further testing showed that this phenomenon was possible because the initial sensory pairing “tagged” co-responsive neurons, making them primed to activate during aversive conditioning.
Optogenetically blocking the mPFC during the aversive learning stage prevented rats from being able to make the later inference. In this case because the image and the unpleasant experience, and indirectly the noise, could not properly become linked in the rats’ minds.
Blocking the output from the mPFC to the amygdala during the test phase also prevented rats from responding to the noise with fear. However, in this case it was because they could not properly recall the inferred memory, even though the association had been made the day before.
At the same time, the rats had no problem freezing in response to the image, indicating that only the higher-order ability of inference is rooted in the physical changes that take place in mPFC neurons.
As Johansen explains, “decades of studying aversive learning in rodents has revealed that the amygdala is a critical site for storing simple emotional memories involving directly experienced associations.
However, our new findings indicate that the mPFC is a central brain region for higher order human-like emotions, which involve internal models and inference.”
“The value of our study,” says Johansen, “is that it opens the door for researchers everywhere to examine the neural mechanisms that mediate higher order emotions, which are more relevant to human psychiatric conditions like anxiety or trauma-related disorders.”
About this fear and neuroscience research news
Author: Adam Phillips
Source: RIKEN
Contact: Adam Phillips – RIKEN
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Prefrontal encoding of an internal model for emotional inference” by Joshua Johansen et al. Nature
Abstract
Prefrontal encoding of an internal model for emotional inference
A key function of brain systems mediating emotion is to learn to anticipate unpleasant experiences.
Although organisms readily associate sensory stimuli with aversive outcomes, higher-order forms of emotional learning and memory require inference to extrapolate the circumstances surrounding directly experienced aversive events to other indirectly related sensory patterns that were not part of the original experience.
This type of learning requires internal models of emotion, which flexibly track directly experienced and inferred aversive associations.
Although the brain mechanisms of simple forms of aversive learning have been well studied in areas such as the amygdala, whether and how the brain forms and represents internal models of emotionally relevant associations are not known.
Here we report that neurons in the rodent dorsomedial prefrontal cortex (dmPFC) encode a flexible internal model of emotion by linking sensory stimuli in the environment with aversive events, whether they were directly or indirectly associated with that experience.
These representations form through a multi-step encoding mechanism involving recruitment and stabilization of dmPFC cells that support inference.
Although dmPFC population activity encodes all salient associations, dmPFC neurons projecting to the amygdala specifically represent and are required to express inferred associations.
Together, these findings reveal how internal models of emotion are encoded in the dmPFC to regulate subcortical systems for recall of inferred emotional memories.
