Evolution + Regulation + Function of
Sleep and Self-repair in Jellyfish
Michael J. Abrams
From jellyfish to human beings, it appears all animals sleep, and yet, for an activity that takes up so much of our lives, we know little about what it actually does, and how it is regulated. Traditionally, researchers have focused on mice and more recently, flies, worms, and fish, to understand the basics of sleep, but even a worm has hundreds of specialized cell types. Perhaps there is a way to reduce the number of variables.
Cassiopea are cnidarians, placing them in one of the earliest branching animal lineages. However, amazingly, Cnidarians have muscle and nuerons much like our own, and a few years back a group of us at Caltech showed that Cassiopea sleep! Unlike all other jellyfish, Cassiopea live upside-down, pulsing stationarilly in the worlds mangroves and are used for study in several fields, from Fluid Dynamics to Evolutionary Genomics.
Cnidarians do not have a brain! Instead, they rely on a decentralized nervous system to control their behavior. Because Cassiopea mostly pulse in place they are well suited for long term behavioral tracking experiments. Cassiopea medusae have radially spaced nerve clusters that contain pacemaker cells, which control their pulsing behavior; these discrete structures are ideal for mapping neurological activity to gene regulation.
Three Primary Research Direcitons:
The basics of sleep regulation: in and out of the lab
Sleep and neruological activity: pacemakers keep the rythm
Sleep homeostasis: neurological proliferation and brain development
A non-traditional system
Cassiopea: a cnidarian sleep model
How is sleep regulated?
Despite lacking a brain, cnidarians possess muscles controlled by neural networks and neurotransmitter systems, including GABA, dopamine, acetylcholine, and melatonin. Further, conserved sleep regulators, including the cGMP-dependent protein kinase 1, PRKG1, and GABA, in Hydra, and a nicotinic cholinergic receptor alpha subunit, CHRNAL-E, in Cassiopea, emphasize that not only is the behavioral state conserved, but so too are components of the regulatory system.
I use the upside-down jellyfish Cassiopea to study the regulation of sleep using light- or mechanical-based sleep deprivation. We then remove the nerve clusters of the animal for RNA extraction and sequencing. Using this appraoch, we have discovered genes that are differentially expressed due to sleep deprivation, and can then investigate the gene’s function.
We have also developed RNAi for use in Cassiopea. This tool gives us the power of targeted gene knock down, and has opened the door to numerous future functional studies.
Nerve clusters (at the tip of each white arrows above), called rhopalia, control the pulsing behavior. Twho have been removed for RNA extraction (below), they would normally appear in the pocket between pie slices. The white streaks mark each slice.
Cassiopea are perfect for studying sleep in the lab and in the field!
Stationary Field Recordings
Snorkling for Cassiopea
The amazingly accessible Cassiopea!
Cassiopea live in the mangroves of southern Florida, were they are widely available. We collect animals, and set up video cameras, collection pens, and a water table, all in their habitat. This supports research in the ecolocial context, adding a degree of confidence that our findings are not simply an artifact of the laboratory environment, a problem experienced by every behavioral biologist
How does neurological activity change during sleep?
There are two major theories for how global brain states arise to generate behaviors like sleep. Either specialized regions control the switch between wakefulness and sleep (a top-down mechanism); or neural networks have an emergent bias towards certain global states that are affected by local regulatory circuits (a bottom-up mechanism). From work in humans and model animal systems, there is a growing appreciation that sleep is regulated globally, regionally, and locally by intersecting mechanisms. However, sleep plays roles that appear specific to the brain, including synaptic homeostasis, neurotransmitter regulation, cellular repair, memory consolidation, and neural plasticity. While sleep across animals plays many roles, would any of these functions of sleep be relevant to an animal without a brain?
Though Cassiopea, as with all cnidarians, do not have a centralized nervous system, they do have nerve clusters, rhopalia, also considered ganglia, that are radially spaced around the bell margin. The ganglia contain pacemaker neurons as part of Central Pattern Generators (CPGs) that initiate muscle contractions, and in recording setups using infrared light and high-speed cameras, the point of muscle contraction initiation can be detected for every pulse. Tracking the position of muscle contraction initiation acts as proxy for local ganglionic CPG activity. From the actograms, we can see that a subset of ganglia leads activity for long periods, but that they exchange over time. A systemic analysis revealed that sleep regulates the homeostasis of ganglionic CPG activity.
Cassiopea electrophysiology: detecting CPG frequency during chemical treatments
We use extracellular electrophysiology recordings to directly associate action potential (AP) frequency of the central pattern generators (CPGs). Measuring voltage changes over time of ganglion nerve clusters reveals the relationship between electrical activity and pulsation rate, and pulse rate is a strong indicator of sleep. We have used known pharmacological targets of acetylcholine, nicotine and DTC, to determine if acetylcholine could be used as a neurotransmitter in Cassiopea xamachana. We found nicotine to increase overall action potential frequency and DTC treatment to decrease action potential frequency, both in a dose dependent manner. These findings provide stronger evidence for the possibility of acetylcholine as the neurotransmitter involved in regulating sleep in the jellyfish Cassiopea xamachana’s cholinergic nervous system.
We use suction electrode electrophysiology to track APs, which can be seen extreanlly as muscle contractions.
Sleep supports neurogenesis!
It has long been known that sleep supports growth and homeostasis, but how it achieves this remains largely a mystery. Cassiopea provides a model for examining sleep’s roles in growth, maintenance, and repair. The Cassiopea nervous system, like other cnidarians, exhibits high cell turnover and regenerative capacity (animals regenerate ganglia if amputated). We found that sleep deprivation significantly reduces cell proliferation in Cassiopea ganglia (see below). This prompted me to investigate brain development in Xenopus, where we found sleep deprivation caused developmental delays in forebrain growth (see below). Together, it is clear that animals rely on sleep in some way to regulate or support cell proliferation, and we are fascinated by this connection. Cell proliferation is the most essential trait of all living things; it defines life, so for sleep to so directly connec to this most basic function of life, we find it profound and are excited to discover the underlying principles and biology.
Here we see the cells that proliferated (green) compared to the total number of cells (red) and see a clear reduction in cell proliferation during the night of sleep deprivation.
We used light or mechanical sleep deprivation once Xenopus tadpoles are old enough to show consistent swimming behavior. The forebrain (F) in particular shows a significant decrease in size.
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Frequently Asked Questions
What is the focus of your research lab?
Our research lab primarily investigates the sleep patterns and self-repair mechanisms of jellyfish, aiming to understand their biological rhythms and implications for marine biology.
Why are jellyfish important for sleep research?
Jellyfish serve as a unique model for studying sleep due to their simple nervous systems and distinct sleep-like states, providing insights into the evolution of sleep and its biological significance across species.
How do jellyfish regenerate?
Jellyfish possess remarkable regenerative abilities, allowing them to recover from injuries and even revert to earlier life stages, showcasing their unique biological adaptations.
What methods do you use in your research?
We employ a combination of observational studies, laboratory experiments, and advanced imaging techniques to explore jellyfish behavior, sleep cycles, and regenerative processes in detail.
How can I get involved in your research?
We welcome collaboration and inquiries from students and researchers interested in marine biology and neuroscience. Please reach out through our contact page for potential opportunities, internships, or partnerships.