Life is full of emotions, from the joy of a sunny day to the pain of heartbreak. Why do people feel happy when they are joyful, like floating on clouds, and suffer deeply when in pain, as if falling into an endless abyss? What changes occur in the brain behind these emotional experiences? How does the brain generate happiness or sadness, and why do emotions cause our hearts to race or leave us overwhelmed by emotional storms? Emotions add color to life, helping us avoid danger and play a crucial role in survival. However, how the brain encodes emotional information has long remained a mystery.
Recently, a groundbreaking study led by Hu Haiyan’s research group at the Institute of Neuroscience, Chinese Academy of Sciences, has taken a major step toward decoding the emotional signals in the brain. Published in *Nature-Neurology* on September 22nd, their paper titled “Using TAI-FISH to observe the emotional valence map of the limbic system of the brain†introduces a new technique called TAI-FISH. This method reveals how different brain regions in the forebrain limb system respond to positive or negative stimuli.
Emotions can be classified in various ways—by intensity, such as strong or weak, or by valence, such as like or dislike. The brain's forebrain limb system, including areas like the cortex, amygdala, and hippocampus, plays a central role in processing emotions. However, previous techniques lacked the resolution to determine whether the same neurons responded to both positive and negative stimuli, or if distinct neurons encoded different emotional experiences.
Under the guidance of Hu Haiyan, graduate students Jianbo and Zhang Qi developed a powerful approach using c-fos, a protein that is rapidly expressed after neural activation. By combining mRNA and protein staining, they could label neurons activated by two sequential emotional stimuli. They also used a tyrosine signal amplification system to enhance clarity, allowing them to distinguish between responses to different emotions at the single-cell level across the entire brain. This technique was named TAI-FISH.
Using TAI-FISH, the team tested various emotional stimuli, such as morphine, chocolate, foot shocks, and restraint. Their results revealed three distinct patterns of emotional coding in the forebrain limb system: separation, coincidence, and mismatch.
For instance, the nucleus accumbens showed a unique pattern where two separate but overlapping groups of neurons responded to likes and dislikes. When exposed to a mix of pleasant and unpleasant stimuli, the response was interlaced. This suggests that the nucleus accumbens may be key in encoding emotional valence. Meanwhile, the paraventricular nucleus of the hypothalamus showed coincident activation for both rewarding and aversive stimuli, possibly encoding emotional intensity.
This study makes two major contributions: first, it overcomes technological limitations by enabling high-resolution, whole-brain analysis of emotional coding at the single-cell level. Second, it identifies specific brain regions involved in emotional processing, offering new insights into how the brain interprets and responds to emotions.
The research was conducted by Ph.D. students Bo and Zhang Qi under Hu Haiyan’s supervision, with collaboration from Zhou Tao, Zhou Tingting, and Chen Yang. It was supported by several funding bodies, including the Chinese Academy of Sciences and the National Natural Science Foundation.
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