Mark Sheffield

Scholar: 2018

Awarded Institution
Assistant Professor
The University of Chicago
Department of Neurobiology


Research Interests

Mechanisms of Memory Formation

The capacity to acquire, store and recall knowledge of the world through experience and use this knowledge to maximize reward and avoid danger is essential for survival. In humans, this ability is fundamental to our sense of self and is in large part what makes us who we are. The brain’s memory systems are also vulnerable to disease and trauma, such as Alzheimer’s disease and post-traumatic stress disorder. If we are to adequately understand memory and treat memory disorders, then we first need to identify neurons that are part of a particular memory, and then determine the underlying neurobiological processes that caused that memory to form and subsequently be recalled.

In order to do this, we use an approach to simultaneously measure the activity of large populations of neurons deep in the brain of mice in a structure called the hippocampus, which is known to be critical for memory function in both mice and humans. We do this while mice are experiencing a virtual reality environment and are forming or recalling a specific memory. In combination with molecular and genetic "tagging" techniques, this allows us to identify which neurons are part of the memory being formed or recalled. We can also use light to control the activity of these particular neurons (optogenetics), giving us a way to control the neural representation of a memory, and test our ideas about how memories are represented in the brain at the level of populations of neurons.

Underlying the formation and recall of these memory representations at the population level are sub-cellular structures, such as axons, dendrites and synapses, that all work together to provide the necessary mechanisms through which a memory representation is formed and recalled. Monitoring and manipulating these structures has, until recently, been impossible in awake animals engaged in memory related tasks. However, our methods allow us to do just that, providing a means to test the role of specific sub-cellular structures and mechanisms in memory formation and recall. Together, our aim is to reveal the features of neural function at the level of populations of neurons down to the level of synapses, that allow for the formation and recall of specific memories, and in this way, we hope to provide insight into the development of treatments for memory disorders such as Alzheimer’s Disease and PTSD.