Student Theses and Dissertations

Xin Jin

Date of Award

2016

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Bargmann Laboratory

Abstract

Early memories are especially robust and enduring, among which the most evocative example is imprinting. Imprinting was first described in newly hatched geese that form a lasting attachment to the first moving object they see. As observed in many animal species, imprinting is a process in which a sensory cue presented early in animal’s life – a critical period – subsequently gains unique access to ecologically relevant behaviors. Little is known about the molecular and neural underpinnings of imprinting. I have used C. elegans as a model organism to study imprinting because of its compact and well characterized nervous system, an armory of available genetic tools, and a versatile behavioral repertoire. Using a ethologically relevant training regime, I found that exposing newly hatched larvae C. elegans to pathogenic bacteria can generate an aversive memory of bacterial odors that is sustained into adulthood (4 days), in contrast to training of adults that results in a medium-term memory that lasts for less than a day. This long lasting aversive memory is specific to the experienced pathogen and has a critical period in the first larval stage (L1), and is defined as a form of aversive imprinting. Through chemical-genetic silencing of candidate neurons, I identified neurons essential for memory formation but not for memory retrieval (interneurons AIB and RIM), and complementary neurons essential for memory retrieval but not for memory formation (interneurons AIY and RIA) (Chapter 2). The RIM memory formation neurons synthesize the neuromodulator tyramine, which is required in the L1 stage for learning. This learning signal is transmitted to the AIY memory retrieval neurons by the tyramine receptor SER-2, which is required for imprinted aversion but not for adult learned aversion (Chapter 3). Tyramine modulation bridges the two subcircuits by linking tyramine production during learning with memory retrieval days later. Functional calcium imaging indicates that early imprinting experience modifies neuronal activity and output of the memory circuit. Among several neurons examined, changes in RIA best express the context and specificity of the imprinted memory (Chapter 4). Combining classical neuroethology, molecular genetics, and functional imaging, I have mapped distinct groups of neurons required for the formation and retrieval of an imprinted memory, defined neuromodulation that enables this critical period learning (tyramine and SER-2), and identified neuronal activity changes associated with memory. These findings provide insight into neuronal substrates of different forms of learning and memory, and lay a foundation for further understanding of early plasticity.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

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