LINDA BUCK LAB -- Research

Our Research

The mammalian olfactory system detects a vast array of chemicals that are perceived as odors. It also detects pheromones and predator odors that stimulate instinctive behavioral and physiological responses. Our lab uses a variety of molecular, genetic, and anatomical methods to study the molecular mechanisms and neural circuits that underlie olfactory effects on perception, instinctive odor responses, and basic drives, such as appetite.

In the olfactory system, signals travel from the nose to the olfactory bulb of the brain to the olfactory cortex, which transmits information to other brain areas. Odor detection in the nose is mediated by ~1000 different odorant receptors (ORs) and 14 trace amine-associated receptors (TAARs). ORs are used combinatorially to detect diverse odorants and encode their unique identities while TAARs have been linked to the detection of amines that induce innate attractive or aversive behaviors. In the nose, sensory neurons each expressing one OR or TAAR are dispersed within one zone but, in the olfactory bulb, their axons converge in a few specific glomeruli, creating a highly organized map of receptor inputs. In the olfactory cortex, this precise organization disappears, but how specific OR and TAAR inputs are organized in this brain area and higher areas is largely unknown.

One of our future goals is to understand how sensory information is organized in the olfactory cortex and higher brain areas to elicit different odor perceptions. Another is to elucidate how the olfactory system stimulates innate responses, such as fear or aggression, or changes in reproductive or stress hormones. We are also interested in olfactory effects on appetite. The olfactory cortex comprises multiple anatomically distinct areas whose respective functions are obscure. In recent studies, we identified one small olfactory cortical area that plays a major role in the hormonal fear response to predator odors. Questions we are exploring now include whether there are selected receptors in the nose that induce specific instinctive responses and whether there are molecularly identifiable subsets of neurons in the olfactory bulb or cortex that are dedicated to producing a specific outcome, such as fear or hunger. We are also interested in the downstream brain circuits that mediate these effects and whether there are parallel or interacting olfactory pathways that induce specific functions or act in opposition to modulate those functions. Other interests include the structure and function of neural circuits that mediate non-olfactory effects relevant to fear and stress and appetite and how those neural circuits may be altered in disease states or with aging.

The organization of OR inputs in the nose and bulb raises a number of intriguing developmental questions. One puzzle is how the olfactory sensory neuron comes to express a single OR gene. Using single cell transcriptome analysis, we found that the neuron can initially express low levels of multiple OR genes (Olfrs) but then transition to the high level expression of only one in the mature state. Future questions include what mechanisms underlie Olfr gene choice and its maturation, what mechanisms determine the expression of Olfr versus TAAR genes, and what distinguishes neurons expressing different TAARs that elicit behavioral attraction versus aversion.