Sensory circuits integrate inputs from the environment, as well as feedback signals from higher brain regions. The interplay of feed-forward and feedback signals is proposed to be fundamental for processing behaviorally relevant information related to expectation, reward, attention and action, during learning and memory recall. Though rich glutamatergic cortical feedback projections innervate inhibitory interneurons in all olfactory bulb layers, to date their specific dynamics and contribution to olfactory processing remains largely unknown. Using multiphoton imaging of GCaMP5 signals in awake head-fixed mice, the Albeanu group recently established that, in response to a diverse panel of odors and across concentrations, corticalbulbar feedback is sparse, odor selective, long-lasting post stimulus offset, spatially diverse and carried by two largely independent bouton/fiber types. Here, the PI, Albeanu, will test the central hypothesis that, in awake mice, cortical feedback contextually modulates inhibitory micro-circuits in the olfactory bulb to enhance discriminability of behaviorally relevant odors. Mechanistically, Dr. Albeanu's group proposes that cortico-bulbar projections respond specifically to stimulus identity and concentration by increasing the odor responsiveness of inhibitory interneurons and de-correlating the responses of mitral/tufted cells to different odors, and that these feedback effect are tuned by odor learning.
Aim 1 : Suppress olfactory cortex activity pharmacologically or optogenetically, while monitoring its effects on the dynamics of two classes of interneurons in the bulb - the granule cells, and the deep short axon - on the mitral cells, the bulb outputs via multiphoton imaging. To achieve further specificity, suppress cortical feedback boutons locally in the bulb while monitoring their targets in the bulb.
Aim 2 : Investigate how cortical feedback changes pre- versus post-acquisition of olfactory discrimination tasks and multisensory reversal learning paradigms. Train head-fixed mice in simple olfactory go-no go and two forced choice tasks, monitor the cortical feedback, and compare the correlations between learned and unfamiliar odors before and after training, as well as responses to the same sensory stimuli under different contingencies.
Aim 3 : Assess the effects of cortical feedback suppression on behavioral performance in olfactory sensory discrimination and reverse learning tasks, and on the responses of granule cells, deep short axon cells and mitral cells via monitoring GCaMP6 signals. The following hypotheses will be tested: (1) cortical feedback binds recent activity patterns in the piriform cortex to ongoing sensory inputs in the olfactory bulb and modulates mitral cell representations to facilitate the identification of behaviorally relevant odors, and (2 cortical feedback broadcasts contextual signals that are used by the olfactory bulb output to help identify rewarded stimuli.

Public Health Relevance

The brain extracts behaviorally relevant information from dynamic environments via feed-forward (bottom-up) and feedback (top-down) processing between the sensory periphery and the cortex. While several decades of research have investigated the feed-forward flow of information, cortical feedback signals remain one of the biggest unsolved mysteries in neuroscience. Systematic study of cortical feedback is thus essential for gaining a clear understanding of the basic network mechanisms underlying sensory processing and contextual learning in the brain. The advent of optical imaging and optogenetic tools offers an extraordinary opportunity to tease apart the roles of feedback connections via chronic monitoring and reversible manipulations of their activity in awake-behaving animals. Further, understanding cortical feedback may have direct implications in the treatment of human neurological disorders arising from imbalances in network excitability and cross-talk between different brain areas.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
Project #
Application #
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Cold Spring Harbor Laboratory
Cold Spring Harbor
United States
Zip Code
Otazu, Gonzalo H; Chae, Honggoo; Davis, Martin B et al. (2015) Cortical Feedback Decorrelates Olfactory Bulb Output in Awake Mice. Neuron 86:1461-77