|
|||||||
| Dr. Murthy will begin at Princeton in Spring 2010 Current Lab |
How does the brain process sensory stimuli and use this information to direct appropriate behaviors? To address this question, I intend to focus my research on the neural codes (patterns of electrical activity) underlying olfactory and auditory perception in the fruit fly, Drosophila.
The goal of my research is to determine how odors and sounds are encoded within the fly brain and to understand how these representations constitute a percept of the fly’s environment -- a percept the fly uses to make important behavioral choices (eg, to move towards a sweet-swelling odor, or to mate with a male fly singing a conspecific courtship song). Drosophila, with its relatively simple nervous system, well-studied behaviors, amenability for in vivo electrophysiology, and large genetic and molecular toolkit offers the ideal system in which to examine questions about sensory coding.
I typically study neurons that are several synapses downstream from the sensory periphery, in order to examine ‘higher-level’ aspects of sensory processing. I am also particularly interested in how nervous systems cope with variability – that is, how reproducible behaviors are elicited given variations in the sensory stimulus and in neural representations of the stimulus (both within and between animals).
OLFACTION: I have been recording from neurons that innervate the mushroom body, the fly’s olfactory learning and memory center. Here, we have discovered that each fly possesses a complement of Kenyon cells (KCs; the principal neurons of the mushroom body) whose odor tuning differs from individual to individual (Murthy et al. Neuron 2008). This is in contrast to both neuronal populations from which their olfactory input derives, and implies that just two synapses downstream from the sensory layer, there may be significant differences in connectivity across genetically identical flies. We speculate that in a system responsible for associative learning, variability in the connection matrix used to generate and learn the representations of significant stimuli may be useful to the species at large.
This study defined a method for measuring the across-animal variability of individual neurons within a large population, using a combination of genetic labeling, single-cell electrophysiology, and computational models. Using similar methods, we will follow up on these results by recording from the postsynaptic targets of the KCs, the mushroom body extrinsic neurons (MBEs). Among this smaller population we can investigate whether or not functional stereotypy reemerges downstream from the KCs, and if so, how. We can also explore how olfactory memories (positive and negative associations) are reliably formed in this structure, given some degree of variability present in the system, and the overall logic of olfactory coding within the mushroom body (ie, which subsets of KCs and MBEs participate in particular representations).
AUDITION: We will be examining how species-specific preferences for courtship song are encoded in the Drosophila nervous system, and how these codes relate to courtship behavior. During courtship (a very robust and reproducible behavior in Drosophila), virgin females display preferences for males of their own species; following courtship and persisting for several hours to days, mated females reject conspecific males. While the importance of auditory cues in mating in Drosophila has been well documented, how courtship songs are encoded within the auditory pathway and how the perception of song leads to different behaviors depending on the song (conspecific or heterospecific) and the state of the female (mated or unmated) is unknown. Songs are produced by courting males via wing vibration, and males of each species (there are >1700 Drosophila species) sing a unique courtship song, consisting mostly of low frequency sinusoidal hums and pulses. Experiments underway address what neurons process courtship song information, and how these neurons are tuned to species-specific song features. Inspired by the recent sequencing of twelve Drosophila genomes and the potential for the development of genetic tools across species, I have chosen to take a comparative approach to understanding the neural coding of courtship song by presenting auditory stimuli from and performing electrophysiological recordings in several of these species.