Neuronal Adaptations during Amygdala-Dependent Learning and Memory

The amygdala, a structure deep in the temporal lobe of the brain, is an essential region for emotional and fearful processing. Neuronal coding in the lateral nucleus of the amygdala (LA) endows the brain with the ability to acquire enduring aversive associations, physically represented by experience-dependent synaptic modifications within a small population of neurons selectively recruited during learning. Understanding the precise mechanisms underlying neuronal selection and plasticity during memory formation has been among the most fundamental questions in neuroscience for the past century. Defining the distribution of neuronal activity would further elucidate the conditions by which memories are expressed and how neurons are differentially recruited into distinct memory engrams. The aim of this thesis was to utilize reliable methods to capture, visualize, monitor and modulate defined neuronal populations to expand our knowledge regarding the above questions. Chapter 1 of this thesis is an overview of the history of progress in understanding fear and eye-blink conditioning. It describes the core principles and particularly highlights recent findings that have been elucidated in the process by which fear memory and motor learning are acquired and encoded. Chapter 2 describes a novel method to study fear memory traces. Arc::dVenus transgenic mice were used to visualize neurons that underwent cellular modifications during fear learning in the lateral amygdala (LA). Our findings demonstrate that intrinsic neuronal excitability is a major driving force for the fear memory neuronal selection. This chapter also demonstrates that the potentiation of glutamatergic synaptic transmission from the thalamic input pathway to the LA is learning-specific, and highly localized to Arc expressing neurons. Chapter 3 reports the distinct pattern of Arc expression following learning in the art of the LA. We find that this subregion demonstrates a chronically enduring plasticity by which neurons in this subregion are uniquely active only upon the acquisition of novel aversive associations. Chapter 4 focuses on the role of somatostatin+ (SOM+) interneurons in the lateral division of central nucleus of the amygdala (CeL) in eye-blink conditioning. We find that the CeL has a regulatory effect on associative eyelid responses, indicating that eye-blink conditioning shares key mechanistic components of fear associative learning responses. Chapter 5 is a general discussion about the outcomes and major conclusions of our studies. In addition, it proposes future approaches that could advance some important unanswered questions in the field.

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