Our work is driven by a desire to understand the neuroscience of cognition and to translate that understanding to outcomes that will improve brain health and quality of life in humans.
Neurodegenerative and neuropsychiatric diseases contribute to reduced quality of life for millions of people. These disorders have a tremendous impact on cognition, affecting aspects such as memory, attention, reasoning, judgement and decision-making. Additional symptoms include impulsivity, apathy, depression and anxiety. Beyond being devastating to individuals and their caregivers, these diseases are a major public health challenge that is accelerating at breakneck pace. Yet despite the great need, over the past three decades few new treatments have been effective, and many major pharmaceutical companies have recently closed their neuroscience divisions to focus on more easily treatable conditions.
Failure of potential treatments for brain disorders occurs repeatedly despite seemingly adequate and appropriate data in preclinical animal models demonstrating that candidate drugs should work. A notable example of this is Alzheimer’s disease, where several drugs have significantly reduced brain pathology in mice and humans but have not led to improvements in the cognitive impairments that are a defining characteristic of this condition. This is in part because assessment of the effect on high-level cognition of recent advances in molecular, cellular and circuit level manipulations in mouse models, in a way that is directly relevant to humans, is an immense challenge. Our work directly addresses this challenge by integrating exploration of molecular, cellular and circuit level brain mechanisms with human disease-relevant cognitive outcomes in mouse models.
Our research combines numerous different techniques for observing and manipulating the brain at the molecular, cellular and circuit level with precision, human relevant analysis of cognition. For example, we use combined with genetically encoded fluorescent indicators to measure calcium signalling or neurotransmitter activity with high temporal precision. We also do causal experiments, using optogenetics or DREADDs to control the activity of individual neurons. In collaboration with colleagues at McGill, we use UCLA miniscopes to visualize individual neural activity in freely behaving animals. And we continue to use many more traditional methods when they are the right way to answer the question. All of these techniques can be combined with our touchscreen-based system for assessing cognition, using similar or often identical tests to those used in humans. And all of this work can be done in normal mice, to understand how the healthy brain achieves cognition, as well as in mouse models of disease, to understand what can go wrong.
If you want to learn more about the details of our research, you can have a look at our full list of publications or see below to get started.