New study sheds light on neuropeptide influence in the brain and behavior

The brain uses neuropeptides, small proteins, in addition to neurotransmitters to send signals between neurons. Neuropeptides are larger than neurotransmitters and can travel far from their source neuron. Despite their importance, the way neuropeptides move around the brain and affect neurons has been poorly understood until now.

On May 10, 2023, Salk scientists published a study in The Journal of Neuroscience revealing the varied influence neuropeptides can have on brain activity. The study sheds light on how the brain communicates in flies and is a crucial step towards understanding the underlying causes of human conditions such as autism-spectrum disorder or attention-deficit disorders.

According to senior author Kenta Asahina, neuropeptides have a greater impact than previously assumed. Neuropeptides affect behaviors like eating, mating, sleeping, and stress levels. Neurons release neuropeptides as signaling molecules, while other neurons receive them via receptors on their surface. It was previously thought that neuropeptides have a general effect on all neurons that express the matching receptor. However, evidence suggests that a specific neuropeptide may control different behaviors by acting on distinct brain circuits.

The study focused on the neuropeptide tachykinin, which is known to increase aggression in animals, including fruit flies, mice, and humans. The researchers aimed to investigate how tachykinin affects neuron communication and animal behavior.

A male fly (left) with an excess amount of tachykinin attacking a female fly (right)—a behavior unlikely when tachykinin levels are normal. Credit: Salk Institute

Researchers at the Salk Institute have shed new light on the role of neuropeptides in the brain. Unlike neurotransmitters, neuropeptides are small proteins that can travel far from the neuron that produced them, but their specific influence on brain activity has remained poorly understood. However, the Salk study, published in The Journal of Neuroscience, reveals that neuropeptides can have a variable impact on behavior, affecting a range of actions, including eating, mating, and sleeping, as well as emotions like fear and stress.

The study focuses on tachykinin, a neuropeptide that has been shown to increase aggression in various animal species, including fruit flies, mice, and humans. By creating a molecular flag that labeled fruit fly neurons with receptors for tachykinin, the team could visualize how the neuropeptide activated certain neurons, leading to specific behaviors in the flies. The study uncovered a novel mechanism for neuronal communication using neuropeptides, where one type of neuropeptide can activate different receptors at different concentrations.

The researchers discovered that tachykinin from a specific type of male neuron affected two separate downstream groups of neurons, which depended on the neuropeptide signal to act. One group of neurons expressed a specific tachykinin receptor and was required for promoting aggressive behavior, while the other group expressed a different tachykinin receptor and was only activated when tachykinin was overproduced. The researchers found that tachykinin affected neurons in different parts of the brain and that the neurons responded differently to varying tachykinin concentrations.

The study’s findings highlight how neuropeptides released from a small group of neurons can reshape activity patterns in multiple downstream groups of neurons throughout the fly brain to impact behavior. These results lay the foundation for future investigations into how neuropeptides impact complex behaviors, which can help us better understand the influence of neuropeptides in human brains, both in health and dysfunction.

Source: Salk Institute

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