Sheffield Lab

Revealing the brain mechanisms of memory


The main goal of our lab is to establish an empirically well-supported unifying model of the neurobiology of complex memory formation and recall from the level of synapses and dendrites to large-scale ensembles of neurons that is based on data obtained from behaving animals engaged in memory-related tasks.

Why memory?

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 diseases, such as such as Alzheimer’s diseases, Schizophrenia, Attention Deficit Disorder, and Stroke, that affect millions of people. If we are to adequately treat memory disorders, then we first need to understand the neurobiological processes that underlie memory function. 


We use a combination of methods to identify neurons that participate in specific memories and measure and manipulate the activity of those neurons, their dendrites and their synapses in real-time in behaving mice before, during and following memory formation and recall:

  • In vivo 2-photon functional imaging of large populations of neurons 
  • In vivo 2-photon functional imaging of dendrites, spines and axons
  • 1-photon optogenetic stimulation and inhibition of genetically defined neurons
  • 2-photon optogenetic stimulation and inhibition of experimenter defined neurons and dendrites
  • Behavior in immersive virtual reality worlds

Outstanding questions we seek to address

  • How does the activity across the hippocampus lead to the formation of a new memory?
  • Do active dendritic signals participate in the formation of a new memory?
  • Are changes in synaptic strength the physical substrate of memory storage?
  • How does inhibition, neuromodulation and glial cell activity contribute to memory formation?
  • How do the above mechanisms contribute to memory recall?
  • How do neural circuits change as memories are altered following memory recall?
  • How does time effect the underlying neural circuitry of a memory?

2P population imaging of CA1 neurons during behavior

2P imaging of CA1 basal dendrites during behavior