Scientists Discover Brain’s “Disappointment Pathway”

September 19, 2014 | Sophie Weiner

Scientists are getting closer to nailing down which portion of the brain makes people with mood disorders more sensitive to negative life events. The breakthrough comes after experiments at UC San Diego which demonstrate new links between certain neurotransmitters and emotions like disappointment. In studies on rodents, scientists discovered that neurons above the thalamus were producing “both a common excitatory neurotransmitter, glutamate, and its opposite, the inhibitory neurotransmitter GABA.” This is rare — there are only two other known parts of the brain which produce both excitatory and inhibitory neurotransmitters. Steven Shabel explains:

Our study is one of the first to rigorously document that inhibition can co-exist with excitation in a brain pathway. In our case, that pathway is believed to signal disappointment.

The part of the brain that produces these neurotransmitters, known as the LHb, has been shown to be more active in experiments with monkeys who are promised a treat and don’t get it.

Depression has been linked with hyperactivity of the LHb. The brains of depressed rodents do not generate as much GABA in this region, causing disappointment to become more pronounced. When the rodents were given anti-depressants, their GABA increased. This research helps us understand in a quantifiable way how anti-depressants chemically alter the brain to relieve symptoms.

“We may now have a precise neurochemical explanation for why antidepressants make some people more resilient to negative experience,” Shabel said. This could lead to much better drugs for treating mood disorders in the future. (Photo: @mollyig)