David Glanzman

My laboratory is interested in the cell biology of learning and memory in simple organisms. In our research we use two animals, the marine snail Aplysia californica, and the zebrafish (Danio rerio).
Work on Aplysia: This invertebrate has a comparatively simple nervous system (~ 20,000 neurons) that provides a valuable experimental model for understanding the cellular mechanisms that underlie simple forms of learning, such as habituation, sensitization, and classical conditioning. Another experimental advantage of Aplysia is that sensory and motor neurons that mediate specific reflexes of the animal can be placed into dissociated cell culture where they will reform their synaptic connections. These in vitro sensorimotor synapses are extremely useful for cellular and molecular studies of short- and long-term learning-related synaptic plasticity. Currently, my laboratory is investigating the mechanisms that underlie the persistence of memory: How are memories maintained in our brains over long periods of time? Recently, we have found evidence that RNA-induced nuclear changes, particularly epigenetic changes, play a critical role in memory storage. Specifically, we have found that a long-term memory can be reinstated after manipulations that erase the behavioral and synaptic memory expressions of the memory; by contrast, the memory cannot be reinstated after its disruption by inhibition of an epigenetic process, DNA methylation. We have also found that long-term memory can be transferred from trained to naive, untrained snails if RNA extracted from the nervous systems of sensitization-trained snails is injected into untrained snails. By contrast, RNA from untrained donor snails does not induce sensitization when injected into untrained recipients. These results challenge the synaptic plasticity model of memory.
Work on the zebrafish: The zebrafish has significant advantages for genetic and molecular studies of behavior, including studies of learning and memory. The zebrafish is amenable to both forwards and reverse genetics. Furthermore, although it is a vertebrate with a complex vertebrate nervous system, it possesses reflexive behaviors that are mediated by relatively simple neural circuits in the spinal cord and brainstem. Finally, zebrafish larvae are transparent, which facilitates the use of optogenetics and advanced imaging techniques to study learning-related neural activity within the intact animal. We study the neural basis of nonassociative learning and memory in zebrafish larvae. In addition, we are investigating olfactory-based associative learning in these organisms.