Investigating the role of the orbitofrontal cortex in learned modulation of innate olfactory behavior

Advantageous innate responses to environmental stimuli are commonplace in bacteria to higher-order animals. Plasticity of these responses allow for adaptation to environmental changes where innate preferences stop conferring survivability and reproductive advantages. The Orbitofrontal cortex (OFC) and other structures related to valence have been implicated in adaptation, but it is unknown if the OFC is required for learned modulation of innate odor preferences. If the OFC is involved in overriding the innate response to odor, then silencing it should block a learned attraction to aversive odor. To test this prediction, we trained mice by pairing aversive odor with reward. Thirsty mice were presented with a choice between drinking small amounts of water in one port with an attractive odor or drinking more water in a port with an aversive predator odor. Preference was measured as the ratio of time spent in the aversive odor trimethyl-3-thiazoline (TMT) port compared to the attractive odor port, 2-phenylethanol. After several days of training, mice learned to increase their preference for TMT. We used chemogenetic silencing of the OFC on a test day to observe any changes in TMT preference. On the test day, control mice with unimpaired OFCs continued to increase their preference for TMT while experimental mice with silenced OFCs decreased their preference for TMT. Based on experimental findings, the OFC is required for using previously learned changes in preference that go against innate valence in choice-based situations. This indicates that the OFC plays a role in modulating valence perception of innate responses