A molecule making a memory positive or negative in the brain

Amazing stuff! We may also have now a better answer why negative memory is stronger than positive memory.

"Researchers ... have discovered the molecule in the brain responsible for associating good or bad feelings with a memory. ...
In 2016, ... discovered that a group of neurons in the brain’s basolateral amygdala (BLA) helps assign valence when mice are learning. One set of BLA neurons was activated with positive valence, as the animals learned to associate a tone with a sweet taste. A separate set of BLA neurons was activated with negative valence, as the animals learned to associate a different tone with a bitter taste. ...

In the new study, the researchers homed in on the importance of the signaling molecule neurotensin to these BLA neurons. They already knew that neurotensin is a neuropeptide produced by the cells associated with valence processing, but so are a few other neurotransmitters. So they used CRISPR gene editing approaches to selectively remove the gene for neurotensin from the cells—the first time that CRISPR has been used to isolate specific neurotransmitter function.

Without neurotensin signaling in the BLA, mice could no longer assign positive valence and didn’t learn to associate the first tone with a positive stimulus. Interestingly, the absence of neurotensin did not block negative valence. ...
In further experiments ... showed that high levels of neurotensin promoted reward learning and dampened negative valence, further supporting the idea that neurotensin is responsible for positive valence. ...
The researchers still have questions about whether levels of neurotensin can be modulated in people’s brains to treat anxiety or PTSD. ..."

From the abstract:

"The ability to associate temporally segregated information and assign positive or negative valence to environmental cues is paramount for survival. Studies have shown that different projections from the basolateral amygdala (BLA) are potentiated following reward or punishment learning. However, we do not yet understand how valence-specific information is routed to the BLA neurons with the appropriate downstream projections, nor do we understand how to reconcile the sub-second timescales of synaptic plasticity with the longer timescales separating the predictive cues from their outcomes. Here we demonstrate that neurotensin (NT)-expressing neurons in the paraventricular nucleus of the thalamus (PVT) projecting to the BLA (PVT-BLA:NT) mediate valence assignment by exerting NT concentration-dependent modulation in BLA during associative learning. We found that optogenetic activation of the PVT-BLA:NT projection promotes reward learning, whereas PVT-BLA projection-specific knockout of the NT gene (Nts) augments punishment learning. Using genetically encoded calcium and NT sensors, we further revealed that both calcium dynamics within the PVT-BLA:NT projection and NT concentrations in the BLA are enhanced after reward learning and reduced after punishment learning. Finally, we showed that CRISPR-mediated knockout of the Nts gene in the PVT-BLA pathway blunts BLA neural dynamics and attenuates the preference for active behavioural strategies to reward and punishment predictive cues. In sum, we have identified NT as a neuropeptide that signals valence in the BLA, and showed that NT is a critical neuromodulator that orchestrates positive and negative valence assignment in amygdala neurons by extending valence-specific plasticity to behaviourally relevant timescales."

Making a memory positive or negative - Salk Institute for Biological Studies

Neurotensin orchestrates valence assignment in the amygdala (no public access)