Forebrain Representations and Control of Sniffing - Project Summary / Abstract Sniffing is an adaptive behavioral strategy to actively sample the olfactory environment. It is crucial to a broad range of functions including finding food, avoiding predators, and recognizing conspecifics. Common to all terrestrial vertebrates, sniffing guides exploration and navigation by co-opting the neural machinery for breathing and increasing the breathing rate to pass air through the nasal cavity and past olfactory receptors. Despite its ubiquity, relatively little is known about the neural control of sniffing. Evidence suggests the forebrain impinges on the brainstem circuitry responsible for basal breathing to modulate the rate and depth of breathing, as is also thought to occur during vocalizations. Based on a wealth of anatomical and functional data, we hypothesize the hippocampus and entorhinal cortex are crucial nodes in the forebrain control of sniffing, establishing an associative link between olfactory sensory information and sniffing motor control to achieve navigational goals. In Aim 1, we will explore how breathing information is projected to the hippocampus by way of a respiratory corollary discharge. Using in vivo electrophysiological recordings in hippocampus and entorhinal cortex, along with optogenetic silencing of identified projection neurons, we seek to identify regions involved in transmitting an efference copy of the breathing rhythm to hippocampus. In Aim 2, we will determine the role of the hippocampus in the initiation of sniffing. Recent evidence implicates regions downstream of hippocampus in the initiation of exploratory behaviors, including sniffing. By using transgenic mouse lines and optogenetics, we will identify neurons in the hippocampus involved in promoting sniffing during active exploration of a novel environment and in an olfactory-guided navigation task. By using modern tools in in vivo electrophysiology and genetic biotechnology, along with cutting-edge machine learning and behavioral analysis, we seek to understand how the hippocampus combines disparate information streams to guide navigational decisions, including the decision to sniff. Overall, these experiments will reveal a role for the hippocampus in a critical adaptive behavior and provide insight into the mechanisms through which the forebrain exerts control over low-level motor controllers and pattern generators.