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Current topics of interest include:
Mechanisms of memory recall & imagination
We can vividly recollect memorable moments from a vacation or imagine ways to rearrange our office while sitting at home. This ability to relive past experiences and simulate potential future scenarios can aid decision-making and also contributes to the richness of our inner lives. The hippocampus is critical for both recall and imagination, but how is unknown.
To study this , we have developed a brain-machine interface (BMI) consisting of a real-time processor of large-scale extracellular recordings combined with an immersive virtual reality (VR) system. This enables us to train rodents to volitionally activate specific hippocampal firing patterns representing remote places. Such activation is a fundamental building block of recall and imagination, and thus we can investigate the underlying mechanisms using the large toolkit available for rodent neuroscience.
In addition, these real-time methods enable precise perturbations of brain activity in a range of other experiments.
Recall & Imagination
The structure of memory representations
A computer stores memories in certain places and according to a particular set of rules. How are memories of places we’ve visited, events we’ve experienced, and other forms of information represented and stored in the brain?
We have used a range of methods - intracellular recording in freely moving animals [2011, 2012] and animals in VR , extracellular recording in freely moving animals , and 2-photon calcium imaging in VR [2020, 2021] - to study the formation and structure of hippocampal memories of space. We discovered a simple mathematical expression that statistically describes how the hippocampus represents spatial environments under a wide range of conditions [2014, 2020].
Brain-wide activity underlying complex cognitive tasks
One of the most useful and impressive features of our brains is the ability to acquire knowledge of novel domains that contain their own rules (e.g. how to use an app, play a game, think about a new subject, perform a new job) and apply what we’ve learned to achieve a variety of goals. The prefrontal cortex, acting in concert with other brain areas, is central to this ability. What enables an animal to perform a particular task?
We study prefrontal circuits and function in animals performing a variety of cognitive tasks [2018, 2020]. In one study, we are recording extracellularly brain-wide using Neuropixels probes in animals switching between performing different tasks, each with their own rules. By analyzing the differences in the activity of prefrontal cortex and other brain areas across tasks, we can screen for neural activity that is specific to knowledge and performance of an individual task.
Developing new methods
We are part of the consortium developing Neuropixels extracellular recording technology [2017, 2021], with the ultimate goal of simultaneous, brain-wide recording in behaving animals. This should be of great value for investigating the distributed neural computations underlying a wide range of cognitive processes and phenomena.
We and our collaborators are also developing technology for fast, real-time processing of large-scale neural data to enable novel brain-machine interfaces for studying cognition  and translational applications.
Previously, we and our collaborators developed the first method to perform intracellular recordings in freely moving animals [2006, 2009, 2011, 2012, 2014].
We are ultimately interested in human memory and cognitive processing in both health and disease (e.g. Alzheimer’s). Therefore, in addition to our work on rodent models of human memory and cognition, we plan to study human neuroscience through collaborations with neurologists, neurosurgeons, neuropsychologists and cognitive scientists, and others.
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