Amygdala positive negative neurons have been identified as two genetically distinct populations that separately encode fearful and rewarding memories, according to a study from MIT published in Nature Neuroscience. These two groups actively inhibit each other, functioning like a biological seesaw that governs our emotional state.<\/p>\n
The amygdala is a small brain structure responsible for processing both positive emotions like happiness and negative ones like fear and anxiety. Within the basolateral amygdala (BLA), researchers found that amygdala positive negative neurons operate in opposing populations \u2014 when one is active, it suppresses the other.<\/p>\n
This balance, or imbalance, may help explain disorders such as depression and post traumatic stress disorder.<\/p>\n
After analyzing all genes expressed in BLA cells, the MIT team identified two genetic markers that distinguish the two populations. The gene ppp1r1b marks reward encoding neurons and is involved in dopamine signaling, which underlies feelings of pleasure. The gene rspo2 marks fear encoding neurons, though its precise function remains under investigation.<\/p>\n
Anatomically, these populations map onto distinct regions of the BLA. The anterior region contains rspo2 expressing fear encoding cells, while the posterior region contains ppp1r1b expressing reward encoding cells.<\/p>\n
Senior author Susumu Tonegawa, Picower Professor of Biology and Neuroscience at MIT, noted that the positive memory cells identified by these genetic markers counter negative memory cells and promise an opportunity to identify effective molecular targets for treatment of emotional disorders such as depression and PTSD.<\/p>\n
Using optogenetics \u2014 a technique that allows selective inhibition of neurons with light \u2014 the team confirmed the distinct roles of each population. When rspo2 neurons were inhibited, mice could not form fearful memories. When ppp1r1b neurons were inhibited, they could not form positive memories.<\/p>\n
Stimulating one population suppressed the other, reinforcing the seesaw model of how amygdala positive negative neurons maintain emotional balance in the brain.<\/p>\n
The mutual inhibition between amygdala positive negative neurons raises important clinical questions. Overexcitable fear neurons or underactive reward neurons could produce abnormally strong feelings of fear or anxiety \u2014 patterns consistent with PTSD and depression.<\/p>\n
Lead author Joshua Kim described the dynamic this way: the brain maintains a seesaw between positive and negative, and anxiety and depression symptoms may result from an imbalance between these two populations.<\/p>\n
Joshua Johansen of the RIKEN Brain Science Institute called the results a major advance, noting that the identification of molecular markers for opposing amygdala cell populations opens the door to targeted genetic access to these emotional networks for the first time.<\/p>\n
Tonegawa’s lab is now investigating the downstream targets of the BLA \u2014 including the nucleus accumbens and the central amygdala \u2014 to map the full circuits that drive behavioral responses to fear and reward.<\/p>\n
This kind of foundational neuroscience research supports the development of future clinical interventions for emotional disorders. Community based research sites play a critical role in translating discoveries like this into trials that reach real patients. Learn more about ongoing research on our blog<\/a>.<\/p>\n