Neuronal Ensemble Mechanisms of Behavior and Plasticity in a Cnidarian

Project Summary/Abstract Deciphering how neuronal ensembles, groups of coactive neurons, control specific behaviors and mental states is important for understanding behavioral disorders caused by mental or neurological condition such as Parkinson’s, Alzheimer’s, epilepsy, schizophrenia, and autism spectrum disorders. Knowledge about how neuronal ensembles lead to specific behaviors and mental states can help us understand their pathophysiology and lead to better development of diagnostics and therapy for these impairments. Specific behaviors and mental states are achieved by transforming the activity of multiple neuronal ensembles into behavioral output. However, it is still unclear how neuronal ensembles interact with each other in order to achieve specific behaviors and mental states, since this is a brain-wide process. The goal of this proposal is to elucidate the neuronal ensemble mechanisms of feeding behavior and neuronal plasticity, at a whole-body scale using the cnidarian Hydra vulgaris, a small and transparent animal with a simple nervous system and a distinct set of complex behaviors. In Hydra, methods to record and stimulate the activity of all neurons and muscle cells have been established. Aim 1 will involve the dissection of functional circuits and neuronal ensembles for feeding. We will image the entire neuronal activity during chemically-induced feeding and then stimulate specific neurons to evoke the behavior. We will also have access to the Hydra connectome, the synaptic connectivity matrix of all the neurons, and confirm it with laser stimulation to build a wiring diagram for feeding. After characterizing the neural circuits for feeding, Aim 2 will characterize the mechanism of feeding habituation of Hydra, a basic form of learning which exist in cnidarians. We will conduct imaging and photostimulation experiments to identify neuronal types mediating habituation. We will further identify the basis of neurotransmission required for the learning using endogenously expressed neuropeptides. The proposed research program will provide a comprehensive understanding of a behavior and generate a complete set of neuroscience tools to explore the role of ensembles in neuronal plasticity and internal states that control behaviors. These findings could therefore impact mammalian neuroscience and provide a basic science evolutionary perspective to better understand the neural basis of behavior and plasticity. As ensembles are impaired in mouse models of epilepsy, Alzheimer’s, Parkinson’s, schizophrenia, and autism, to better understand their basic biology could potentially impact the study of the pathophysiology of many disease processes.