Brain cells communicate to help us find food
Brandon Bastien was the lead author on this study. Brandon graduated from Swarthmore College with a degree in neuroscience with high honors. He then obtained his PhD in Neuroscience from the University of Pennsylvania in the Hart Lab and has continued his work as a postdoctoral researcher. Since joining the Hart lab, his focus has been on defining the circuitry underling how C. elegans respond to food deprivation stress and how certain synaptic proteins, some of which have orthologs in humans (like neurexins and casprs), and neuromodulators may distinctly act within this behavior-generating circuit. Outside of lab, he enjoys TV shows, football, Eurovision, and traveling.
or technically,
Distinct neurexin isoforms cooperate to initiate and maintain foraging activity
[See Original Abstract on Pubmed]
Authors of the study: Brandon L. Bastien, Mara H. Cowen, and Michael P. Hart
The World Jigsaw Puzzle Championship is an annual event where individuals, pairs, and teams compete to solve puzzles the fastest. In the final team round of the Puzzle Championship, groups race each other to solve two 1000 piece puzzles the fastest.
Neuroscientists around the world are also puzzlers, of a slightly different variety. The puzzles they aim to piece together are the human brain and other nervous systems/brains. The human brain contains billions of pieces each fitting together to reveal an image of who we are. In the brain, each piece is a cell, a basic unit. Just like border pieces and ribbon pieces are different types of puzzle pieces, the brain has different types of pieces/cells as well. One type of brain cell is called neurons. Neurons communicate with each other by forming connections through the small gaps called synapses. The main type of synapse is chemical synapses. In the chemical synapses, the brain uses molecules which are chemicals that are transferred from one neuron to another passing along messages. One neuron releases the chemicals which travel across a small gap before binding to the receptive neuron to transmit signal/information. Chemical synapses may be modified by structural properties, including how close together the neurons are at the synapse, how large the synapse is, and more. Synaptic structure is held together using adhesion molecules that form bridge-like structures that facilitate and modify communication at the synapse (Figure 1). The synaptic structures may modify how the chemical molecules messengers communicate with the receptive neuron. The string of specific neurons fitting in with each other makes neural circuits. The circuits have a function of regulating behaviors such as walking, eating, or sleeping. When neuroscientists are able to understand how our neuron pieces fit together through synapses to regulate behavior, for even a small part of the brain, it is also a win with the price of improving human lives.
Neurexin, a synaptic structure, forms part of the bridge between neurons to enable communication. There are different versions of neurexin. Alterations to neurexins affect many behaviors associated with neurodiversity, such as autism spectrum and schizophrenia. It is important to understand how neurons communicate through synapses to mediate circuits that regulate behaviors.
Brandon Bastien, a NGG graduate, focuses on understanding how brain pieces fit together through the synapse to regulate behavior, specifically foraging behavior. Foraging behavior, the search for food is an essential behavior that is conserved in all animals. Since the human brain has billions of pieces, Brandon uses a smaller animal, a small worm C. elegans that has just 302 puzzle pieces (compared to the human brain, think of this as a puzzle for a child). C. elegans also have conserved genetic or hereditary information, synaptic structure, synaptic molecules, and foraging behaviors. In the worm the piece that is known to drive foraging behavior is the pair of neurons named RIC (one on left and one on right). It was known that the RIC neurons use chemical synaptic messenger octopamine for foraging behavior. It was unknown if the synaptic cell adhesion structure neurexin is important for foraging behavior or the connections made to or by RIC neurons
Brandon asked how the synaptic protein neurexin affects the foraging behavior of C. elegans. Two versions of neurexin in the human and the worm are called γ version and α isoforms (Figure 2). The two different versions are both located in the synapse and have shared parts, but are different sizes (one longer and one much shorter). He used genetic manipulations by deleting the different versions of neurexin hereditary information to test if neurexin modifies foraging behaviors. Foraging behavior, the search for food, is quantified by the high activity level of the animal. The worms were placed in environments without food and were videotapes with a microscope over the course of eight hours to evaluate their activity. Higher activity indicates food search and a lower activity indicates less food search. Similarly to humans, we will move source food when we are hungry. The movement of the worms off food was compared to animals that were on food. Animals without food will have a higher movement activity to look for food and the animal with food moved less since they did not need to find food (Figure 3 ).
Brandon identified the roles for different neurexin versions in foraging behaviors by asking how the food searching changed when he deleted them. When the short γ version of neurexin was deleted, in the absence of food, the animals had a temporal effect. Within the first hour, animals that were missing the short γ version of neurexin and were food deprived had comparable movement when compared to animals that were fed. However, from hours 2-8, animals that were missing the short γ version of neurexin and were food deprived increased their movement significantly when compared to feed animals. This indicates that the γ version of neurexin is important for starting the food search behavior, but it is less important for maintaining the later hours of food search. When the α version of neurexin was deleted, in the absence of food the worm moved more than the worms that had food in the first hour in an attempt to find food, but then decreased their movement in the later hours for the entire eight hours. This implies that the α version of neurexin is important for maintaining food search behavior, but is less important for starting the food search behavior. This is the first time that the different versions of neurexin were found to both impact foraging behaviors. The different versions of neurexins have different functions in the food search behavior with γ version of neurexin being important for starting food search and the α version of neurexin being important to maintain continued food search (Figure 4). The different forms of neurexin cooperate through different functions and cooperate to start and continue this foraging behavior.
The next question Brandon asked was how were the different forms of the synaptic structure neurexin affecting different phases of the foraging behavior interact with the chemical synaptic signaling molecule octopamine. To test this question, Brandon used animals that were missing octopamine. In animals that were missing octopamine in the absence of food, the worms had less activity in the first two hours then had increased activity in the remaining eight hours when compared to animals on food. This indicates that the synaptic molecule octopamine is also important for starting food search behaviors, but is not required for maintaining food search behaviors. Therefore, both the γ version of neurexin and octopamine signaling are both essential for starting foraging behavior. Additionally, neurexin in neurons is needed for octopamine function. May want to mention that when branded deleted the alpha isoform, there were fewer RIC synapses - referring back to intro on chemical synapse structure?
Brandon has shown that RIC neurons have synapses that have synaptic structure neurexin and synaptic molecule octopamine that functions in regulating foraging behavior. In addition, the paper identified the different and collaborative roles the different forms of neurexin have in foraging behaviors with the γ version starting foraging behaviors and the α version of neurexin maintaining the foraging behavior in the absence of food. Lastly, Brandon showed that the synaptic structure neurexin is required for the synaptic molecule octopamine to function showing how team work in synapses regulates behavior. This work provides insights into how neurons form communication through synapses to alter circuits that regulate behavior. Neuroscientists have more work to do in understanding how the different puzzle pieces of our brain fits together.
About the brief writer: Sophia M. Villiere
Sophia is a PhD Candidate in Michael P. Hart’s lab in the Neuroscience Graduate Group at the University of Pennsylvania, studying how autism associated gene mutations affect neuron morphology and behavior.