Identification of the stimulus features represented by neuronal activity, and understanding the fidelity of this representation, are central to understanding how the brain processes the sensory world. In the mammalian olfactory bulb, mitral/tufted (M/T) cells both receive synaptic input from sensory neurons, and serve as the principal output to central brain structures. Due to physical constraints, odor intensity (concentration) at odorant receptors in vertebrates is likely to vary much more slowly than stimulus intensity in other sensory modalities such as vision or audition. Because of this speed limit, the precise timing of action potentials (APs) will not track rapid, millisecond-timescale changes in stimulus properties as in other sensory systems. Rather, the extra "bandwidth" afforded by precise AP timing could encode other olfactory stimulus features, such as identity or context. If odor identity is encoded in AP timing early during a stimulus response, and this timing is reliable across identical stimuli, behavioral response latencies could be minimized11. Across respiratory cycles, an identical ensemble AP response could serve to confirm odor identity. Alternatively, directed changes in this response across cycles could convey novel information in each respiratory cycle about a complex stimulus. Here I propose to test the hypotheses that ensemble AP timing encodes features of odor stimuli in the mouse olfactory bulb, and does so in a dynamic fashion across respiratory cycles.
Olfaction permits animals to detect molecules in their environment with astounding precision, evoking emotion and memory, and facilitating eating, mating, and escape from predators. In order to understand these behaviors, under both normal and pathological conditions, we must understand the mechanisms of olfaction. However, scientists still do not understand the nature of the signals sent from one neuron to another, and how these signals enable the brain to make sense of the sensory world. The olfactory bulb serves as the first organ of olfactory transduction, and mitral cells are the principal output of the bulb. Many thousands of mitral cells are simultaneously active during olfactory processing, but the means by which these cells can collectively encode smells remains unclear. In other fields of neuroscience, simultaneous (ensemble) recordings of many cells have elucidated the mechanisms by which cells coordinately transmit information about stimuli. In the olfactory bulb such techniques have received limited use. I propose to make such ensemble recordings from mitral cells to understand these mechanisms. Specifically, I propose to evaluate two hypotheses: the first is that precise action potential timing in mitral cell ensembles is important to the encoding of a stimulus. The answer to this question is important because it will reveal whether the timing of action potentials can carry what information about an olfactory stimulus rather than just when or where information. It will also inform the research community as to whether mitral cell serve as independent channels that can be monitored separately, or whether the ensemble activity is a gestalt, more than the sum of its parts. The second hypothesis is that mitral cell responses can change over time to facilitate the extraction of stimulus information. This represents a challenge to the dogma that the respiratory cycle is an invariant snapshot of the current odor environment. The ability to smell is very important to quality of life in humans. However, we know very little about how smell works, why some people (or animals) are better at smelling than others, or how we might create prosthetic devices to restore a sense of smell (and taste) in the olfactory-impaired. The basic research proposed here will help to solve these problems.
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