Whitman Center Lab Bets on Hydra to Unlock Nervous System Architecture

Whitman Center Lab Bets on Hydra to Unlock Nervous System Architecture

By Sarah Lawhun

Hydra are small, soft, tentacled animals that cling to leaves, rocks and debris in ponds and lakes. While they’re only a few millimeters in length, Hydra species have among the most ancient nervous systems on the planet and, amazingly, are immortal. Individual animals have never been observed to age and, if cut in half, simply regenerate the other half of their body.

Hydra vulgaris, a small, freshwater organism. Rafael Yuste’s lab aims to crack Hydra’s neural code by recording the activity of each neuron and decoding how it relates to behavior. Credit: Rafael Yuste

Hydra have been studied at the MBL for more than 100 years, beginning with the work of Ethel Browne and Thomas Hunt Morgan in the late 19th and early 20th centuries. Scientists have established the structure of their nervous system: a few hundred to a few thousand branching nerve cells that control their muscular movement.

Due to its experimental simplicity, Hydra’s nervous system has attracted the attention of Rafael Yuste, professor of biological sciences and neuroscience at Columbia University and 2018 Whitman Center Fellow.

A couple of years ago, Yuste’s group used calcium imaging to describe how Hydra’s two nerve nets control its basic muscular movement. Hydra has two layers of muscle that cover the length of its tube-like body, each with a separate nerve net.

Yuste’s lab then classified the full range of behaviors of the main laboratory species, Hydra vulgaris. In a recent paper in eLife, they described their algorithm for automatically analyzing videos and classifying pre-determined Hydra behaviors, labeling each behavior with a name, such as “somersaulting” or “inchworming.”

In the summer of 2017, Yuste nucleated the  Hydra Lab in MBL’s Whitman Center — a fluid group of 7 to 14 scientists from several institutions who have expertise in neurobiology, molecular biology, development, optics, computational biology, and other fields. The goal of the lab is to crack Hydra’s neural code. To do this, they are developing a mathematical model that records the activity of each Hydra neuron and each muscular activity, in order to predict the animal’s behavior.

To create the model, they’re exploring different ways to edit Hydra’s genes, using fluorescent tags as reporters of neuronal activity. By inducing certain behaviors using chemical stimuli, and, ultimately, directly manipulating behaviors, they hope to determine which neurons and muscles coordinate to produce specific behaviors.

“We want to look more closely at Hydra’s nervous system to find out what the benefit is of having two nerve nets,” says Yuste. “It’s possible that it needs to coordinate both sets of muscles to perform some behaviors. Knowing this could help us test the theory that evolution invents a nervous system when the animals get too large for movement to be controlled through non-coordinated, local interactions.”

Because Hydra aren’t studied as much as, say, mice, Yuste and the Hydra Lab are pioneers in fully understanding its nervous system — enough to create a computational model to describe and even to reverse-engineer it, which means deciphering it neuron by neuron and conceptually putting it back together again in a working model.

“I think that’s what science is about: asking questions and making observations for the first time,” says Yuste. “It’s fun to delve into a system where you don’t know much. It’s like exploring a new country or territory.”

Yuste’s enjoyment of curiosity-driven, fundamental research is not the only reward he finds in studying Hydra’s nervous system.

“Historically, when people ask these kinds of fundamental questions, they’re helping us grasp the most basic functions of life,” says Yuste. “It’s building the foundation for us to understand the mechanisms behind human diseases and their treatments.”

Top photo: Rafael Yuste of Columbia University presents the Hydra Lab’s research at the Whitman Fellows’ Brown Bag Lunch Series last summer at MBL. Photo: Diana Kenney