Inhibitory neurons in the amygdala can flexibly shape emotional learning and memory

Neurons that specifically reduce and modulate electrical brain activity have a greater influence on emotional memories than previously thought. DZNE researchers came to this conclusion based on studies in mice. A team led by Bonn-based neuroscientist Sabine Krabbe reports these findings in the journal Nature Communications, along with experts from Switzerland and Israel. The study’s results shed new light on how the brain generates and stores memory content and may help to elucidate the neural mechanisms of anxiety and post-traumatic stress disorders.

Memories and feelings arise from the brain’s activity. Behind this lies a complex interplay of countless neurons that communicate with each other via electrical impulses. Their chorus is finely orchestrated: similar to how green and red traffic lights regulate traffic flow, the level of brain activity is based on some neurons boosting brain activity and others putting the brakes on in a controlled way.

“In the brain, this balance between stimulation and inhibition must be constantly adapted. This happens, for example, when we learn to deal with stressful situations. It also occurs when we recognize that a threat has passed,” explains Dr. Sabine Krabbe, a research group leader at DZNE’s Bonn site. “In this context, we looked at processes in the amygdala. This brain region is key for regulating emotions and resulting behaviors.”

Observation of individual cells

Using mice as a model, Krabbe’s team explored these brain processes with miniature microscopes weighing less than two grams.

“A mouse can easily carry such a device on its head and move around freely with it. This allows us to observe what the animal is doing at a given moment—and what is happening in the amygdala at the same time,” explains the neuroscientist.

“This allows us to capture the activity of individual neurons. We also have techniques for distinguishing between different cell types, which enables us to precisely correlate behavior and neuronal activity. The whole procedure is quite complex, both experimentally and technically.”

In their experiments, the researchers observed how mice processed emotionally significant experiences. Initially, the animals associated an acoustic signal with an unpleasant event and responded with a freezing reflex. Later, however, they learned that the sound cue no longer indicated danger and adjusted their behavior accordingly. This learning process was also reflected in changes in activity patterns of individual neurons in the amygdala.

Surprisingly diverse

The researchers focused in particular on “inhibitory neurons,” which suppress brain activity by releasing a certain neurotransmitter.

“Research into emotions and memory has so far concentrated mainly on excitatory neurons. These stimulate brain activity and are also significantly more numerous,” says Krabbe.

“Inhibitory neurons have been somewhat neglected in research to date. They are traditionally seen as passive players in neural activity. However, our study shows that they are more complex than previously assumed and that they actively contribute to memory formation in different ways, depending on the situation.

“Their inhibitory effect does not follow a rigid program; instead, it is flexible. These cells are involved both in learning unpleasant associations and in recognizing when a previously threatening situation becomes harmless. This is a previously unknown aspect of neuroplasticity, in other words, of the ability of a neuronal system to adapt. And, it is reasonable to assume that such mechanisms also exist in the human amygdala.”

Research into psychiatric disorders

These study results go beyond insights into fundamental brain processes, emphasizes the Krabbe. “Our findings change our understanding of how memories associated with emotions are regulated in the brain. This opens up new avenues for researching the mechanisms of psychiatric illnesses in which such memories become unbalanced. This would apply, for example, to anxiety disorders and post-traumatic stress disorder. In the long run, our findings may help to identify targets for therapies.”