Sensory transduction begins with electrical signals in primary sensory cells. Before these signals can be used to direct behavioral choices, they must be reformatted, or transformed. This is the job of the brain's sensory-processing circuits. Sensory transformations occur progressively, as information moves from primary sense organs toward motor-planning regions. Our research is aimed at understanding the fundamental principles governing these transformations, their mechanisms, and their functions.
Drosophila as a Model for Sensory Processing
The brain is generally studied either at the level of individual neurons and synapses or at the level of neural systems. We want to bridge the gap between these levels of explanation. This is most feasible in a brain that contains a small number of neurons, where each neuron (or type of neuron) is easily identifiable, where it is possible to make both intra- and extracellular recordings from identified neurons in an awake organism, and where genetic tools permit very specific in vivo manipulations of cellular and circuit properties. We use the fruit fly Drosophila melanogaster as a model organism because it meets all these criteria.
Olfactory Processing: Early Events
Probably the most experimentally tractable region in the Drosophila brain is the antennal lobe, thus much of our research has focused on this region. The antennal lobe is the first brain relay in the olfactory system, analogous to the mammalian olfactory bulb. It receives input from a well-characterized population of olfactory receptor neurons (ORNs), and its anatomy is highly organized: All the ORNs that express the same odorant receptor gene project their axons to the same compartment (or glomerulus). In total, the antennal lobe has about 50 glomeruli, each corresponding to a unique odorant receptor gene. ORNs make excitatory synapses with second-order neurons called projection neurons (PNs). Each PN receives direct ORN input from just a single glomerulus and lateral input from other glomeruli via local interneurons. The orderly anatomy of this circuit, and the ability to label identified neurons within the circuit with green fluorescent protein, make it a particularly useful model microcircuit.
We have described three fundamental computations that occur in this circuit. First, each glomerulus pools independent signals from ~40 ORNs, each of which represents an independent snapshot of a particular region of olfactory space. We showed that this pooling step improves the signal-to-noise ratio of olfactory signals. Second, within each glomerulus, we showed that weak ORN firing rates are strongly and preferentially amplified. This amplification is likely to be useful because weak ORN firing rates are more common than strong ORN firing rates; therefore, they should logically occupy most of the system's dynamic range. Boosting weak signals in this way should tend to protect them from noise added at later processing stages. Third, lateral inhibitory interactions between glomeruli perform an important gain control function. We showed that this form of gain control decreases redundancy among glomeruli, improves odor discrimination, and allows odor identity to be encoded in a manner that is robust to concentration.
Olfactory Processing: Late Events
We know little about higher olfactory brain areas in any organism, mainly because of their anatomical complexity. Neurons from each glomerulus send diffuse projections into higher brain regions, where they could potentially make synapses onto a large fraction of target neurons, although their actual pattern of connectivity is not known. It is thought that higher olfactory neurons combine inputs from multiple glomeruli, but we do not know the principles that govern which inputs are combined, or how they are integrated. Because the vertebrate olfactory system contains 1,000 glomeruli, the number of possible glomerular combinations is large, making this a difficult problem.
Drosophila have only 50 glomeruli, and we can genetically tag neurons with ease. This should allow us to define the fundamental principles of higher olfactory processing in Drosophila, which should ultimately guide studies in other species. My laboratory is currently beginning to use these tools to investigate olfactory processing in the lateral horn, the higher olfactory brain region that mediates all unlearned olfactory behaviors in the fly.
Time is a critical parameter in all sensory stimuli. This means the brain must be able to faithfully encode temporal information on various time scales. There are likely to be multiple mechanisms that make neurons selective for the temporal features of a stimulus.
The auditory system is an ideal setting for investigating neural coding in the time domain because auditory stimuli are simply movements in time, that is, movements of the tympanal membrane (in vertebrates) or movements of the antenna (in Drosophila). All the information that the brain extracts about a sound is contained in the temporal pattern of these movements. For this reason, auditory neuroscience has yielded important insights into how neurons encode stimuli in time. However, we do not fully understand how neurons extract the relevant features of sounds.
Our experimental preparation allows us to make in vivo intracellular recordings from central auditory neurons whose connectivity within the circuit can be fully characterized. My lab is beginning to use this preparation to learn how central neurons can acquire selectivity to acoustic features. We hypothesize that selectivity will reflect the pattern of connectivity from auditory receptor neurons as well as the biophysical properties of central neurons and synapses.
Partial support for these projects was provided by grants from the National Institutes of Health, the Human Frontier Science Program, the Pew Scholars Program, a Beckman Young Investigator Award, a McKnight Scholar Award, and a Sloan Research Fellowship.
As of July 30, 2013