Daniel J. Millman, MS - US grants

? DESCRIPTION (provided by applicant): Identifying dangerous or rewarding elements in an animal's surroundings is an important - if not primary - function of sensory systems. This holds particularly true for the mouse olfactory system since odors convey crucial information about predators, mates, kin and food. Thus, the olfactory system needs to effectively determine which odors are present as well as whether each odor has a positive or negative association, termed valence. Currently, we have little knowledge of how odors and valence are processed in the olfactory cortex of behaving mice. Direct sensory input from the olfactory bulb reaches multiple cortical areas and the output of many of these areas converges on the posterior piriform cortex (PPC). The PPC is a potential link between incoming odor information and the representation of valence in higher-order brain structures. Although its anatomical connections suggest that PPC plays an important role in transforming sensory input into a representation that is compatible with behavioral variables, such as valence, the nature of odor coding in the PPC is not yet known. To address this issue, I will combine head-fixed olfactory tasks that I have developed with sniff monitoring and multi-tetrode recordings of individual neurons in mice. This project aims to (1) dissociate the contribution of identified neurons to odor coding in PPC at high temporal (sub-sniff) resolution and (2) examine the coding of valence by individual PPC neurons as new odor-reward contingencies are learned. Preliminary data indicate that sniffing imposes a temporal structure on the odor responses of PPC neurons that has not previously been observed. This knowledge allows us to design much more sensitive analyses to assess features of odor and valence coding, which have not previously been accessible. I will use channelrhodopsin-tagging to distinguish between excitatory and inhibitory neurons to examine their respective contributions to coding. Support for the hypothesis that excitatory neurons are narrowly tuned relative to inhibitory neurons would advance a model in which excitatory neurons respond only to the few odors that excite the neuron enough to overcome broadly tuned inhibition. Furthermore, the ability to analyze sniff-locked pre-decision activity with high temporl resolution will allow us to assess whether PPC neurons have the capacity to contribute to decisions about odor valence. Finally, monitoring the activity of PPC neurons as mice learn odor-valence associations and as these associations are reversed will allow us to directly test whether these neurons are sensitive to valence and, if so, whether valence sensitivity is odor-specific.