Mechanisms and Meaning for Smell
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Sandeep Robert Datta, M.D., Ph.D.
Professor of Neurobiology
Harvard Medical School
The brain allows animals to successfully interact with a natural world that is rich with opportunity and rife with danger. These interactions are mediated by sensation and movement, which are used by animals to learn about their environment and to make useful predictions about the future. A major challenge facing neuroscience is to understand how the brain builds meaningful patterns of movement in unrestrained settings where animals can freely sense and act based upon their own motivations and desires. The main goal of the Datta lab is to reveal how the brain composes natural behaviors that are endowed with purpose.
The Datta lab embraces the perspective of the ethologists: if we are to understand how the brain works, we need to think about the actual problems it evolved to solve. Addressing this challenge means studying natural behavior — the kinds of behaviors generated by animals when they are free to act on their own internally-generated goals without physical or psychological restraint…really, the kinds of behaviors you see when you watch lions in the wild, mice in a home cage, or humans at the mall. Importantly, when one observes animals expressing spontaneous, self-generated behavior, it is clear that much of what they are doing is exploring the world — using movement to sense what is out there, and taking advantage of sensation to inform future movements. Answering the question — how does the brain give rise to natural behavior? — therefore requires understanding how sensory and motor systems are usefully intertwined to support cognition.
We therefore study how the brain processes information related to smell (arguably the most important sense for the mice we study in the lab), dissect the basic neural mechanisms that give order and structure to complex natural behaviors, and ask how olfactory and motor systems influence each other to give animals a full account of the world around them. In practice this means we watch mice as they generate (often odor-driven) behavior in both simple and complex settings, monitor and manipulate gene expression and neural circuit activity, and thereby define relationships between brain and natural behavior. Our experiments are designed to address how the brain constructs behaviors that are sensitive to external cues and internal drives, reflect individual experience, develop characteristically over the lifespan, and dynamically evolve through learning; our work takes advantage of an interdisciplinary toolkit including modern techniques — such as functional imaging, closed-loop optogenetics, cell fate mapping and single-cell sequencing — and approaches of our own making — such as machine learning-based methods for decomposing body language into its constituent syllables and grammar.
It is our hope that by exploring neural circuits in which sensation and action intersect — and by using ethology as a lever — we can gain purchase on the fundamental problem of how the brain gives rise to natural behavior.
Summary
Nearly all animals depend upon smell to usefully interact with the world. Although underappreciated, smell is also critical to humans, as patients with olfactory loss face substantial additional risks for injury, psychiatric disease, and death. However, smell remains a mystery — we know little about how odor information is organized in the brain, and even less about how odors are linked to perception. Here I review the canonical mechanisms thought to enable olfaction, and discuss recent surprises that are revising our ideas about how our sense of smell might work. I will also discuss the future of olfactory research, and the ways in which what we learn about smell might influence the ways we think about our other senses.
Learning goals:
- To be able to describe the function of the olfactory system
- To desribe new features of neural circuits supporting olfaction
- To describe the role of gene expression in shaping olfactory system function
https://videocast.nih.gov/watch=55039
This page was last updated on Monday, April 7, 2025