Understanding the neuronal mechanisms of closed-loop olfaction

Project Summary
In nature, sensory perception and motor processing operate in closed-loop. Self-generated movements impact
sensory input, and sensory inputs guide future motor commands. Through experience, the brain may learn the
reciprocal relationship between sensory inputs and movements in the form of generative sensorimotor models
that predict the sensory consequences of upcoming actions. In vertebrates, olfaction is intrinsically linked to
motor action through sniffing, and just as for other sensory modalities, via head and body movements. Due to
technical challenges, however, most studies in laboratory settings have probed olfactory processing during
passive odor sampling. Even when investigating odor-driven navigation, the effect of movements on odor
responses has rarely been analyzed. Here we will test the central hypothesis that, in closed-loop olfaction,
mice generate olfacto-motor predictions on the sensory consequences of their actions, which further guide odor
sampling movements. At the circuit level, we hypothesize that specific olfactory cortex circuits represent olfacto-
motor prediction errors, computed by comparing odor input and movement-related predictions of the expected
odor input. We plan to test these hypotheses using a novel closed-loop odor localization task (Smellocator)
developed in our group, together with a rich repertoire of sensorimotor perturbations, state-of-the-art recordings
and cell-type circuit analysis tools with increasing levels of specificity.
● To this end, we will first investigate whether under closed-loop coupling of movements and odor sensing, mice
detect olfacto-motor errors, and further compensate for them. In the Smellocator task, head-fixed mice learn to
steer a lightweight lever with their paws to control the lateral location of an odor source according to a fixed-gain
sensorimotor mapping rule. In catch trials, we will transiently alter the relationship between lever movement and
odor displacement via a range of precise, unexpected sensorimotor perturbations. Preliminary data indicate that
expert mice successfully compute sensorimotor prediction errors, and quickly engage in fine corrective
movements triggered by these perturbations in an individual specific manner.
• Then, we will investigate whether the olfactory cortex (piriform vs. anterior olfactory nucleus) represents olfacto-
motor prediction errors in face of transient surprises. We will check whether brief sensorimotor perturbations
trigger sudden changes in cortical activity (mismatch responses). We will refine our analysis to determine if
different semilunar and pyramidal cells types (e.g. Netrin+, Cux1+, Tbr1+, Tle4+) represent primarily sensory
inputs vs. olfacto-motor errors by combining distributed recordings and modern genetic labeling strategies.
• Finally, we will investigate whether the olfactory cortex enables adaptation in the presence of persistent olfacto-
motor errors. We will change the sensorimotor mapping rules in blocks of trials, and across behavioral sessions,
and compare the roles of specific cell types in supporting sensorimotor adaptation taking advantage of flexible
optogenetic suppression strategies.

Grant Number: 5R01DC020842-04
NIH Institute/Center: NIH
Principal Investigator: Dinu ALBEANU