A fundamental step in understanding sensation is understanding how neural circuits in the brain transform patterns of sensory neuron activity into robust and efficient representations of the external world. Sensation is an active process in which the detection and initial encoding of sensory information is dynamically modulated by sampling behavior and behavioral state. Understanding how central circuits process sensory information in the context of active sampling is critical for understanding the neural basis of sensation in the behaving animal. The goals of this project are to understand how neural circuits in the mammalian olfactory bulb transform sensory inputs in vivo and in the context of active odor sampling. We will ask how certain bulb networks - in particular those mediating interactions between glomerular modules (interglomerular circuits) and those mediating inhibition within a glomerulus (intraglomerular circuits) shape the patterns of olfactory bulb output that are transmitted to cortex as a neural code for odor information. We will also ask how active 'sniffing' of odors at high frequency changes the operation of these circuits. We will use an innovative toolbox of genetic, optical and electrophysiological approaches that we have optimized for the in vivo dissection of circuit function, applied primarily in the awake, head-fixed mouse. There are two broad Aims designed to generate an understanding of the how the olfactory bulb network transforms sensory inputs acquired by the behaving animal.
The first Aim focuses on interglomerular circuits and will map how these circuits influence mitral cell output from olfactor bulb glomeruli and how they are organized with respect to the glomerular odor map. We will use optogenetic activation of sensory input to genetically-tagged glomeruli expressing different odorant receptors, combined with selective imaging of excitation and inhibition from mitral cells innervating these glomeruli.
The second Aim focuses on intraglomerular inhibition and will ask what role this inhibition plays in shaping the input-output functions of mitral cells during natura odor sampling. We will quantitatively compare responses of periglomerular versus mitral cells to optogenetically- and odorant-evoked inputs using imaging in the awake mouse, and perform whole-cell recordings from mitral cells during selective optogenetic suppression of intra- (but not inter-) glomerular inhibition. The overall impact of this project will be to advance a mechanistic understanding of how central circuits transform sensory inputs into the neural patterns of activity that underlie perception and an understanding of how these circuits function during behavior.
The sense of smell presents unique problems to the nervous system in terms of stimulus detection, neural encoding and recognition of complex stimuli; understanding how the brain solves these problems will likely lead to general insights into how the brain processes information. This project investigates how neural circuits in the mammalian olfactory bulb transform olfactory sensory inputs in the intact animal and in the context of active odor sampling. Understanding how neural circuits function during the active sampling of sensory information is fundamental to understanding the neural basis of sensation in any modality including vision, audition or somatosensation. These insights could be important in developing improved prosthetic sensory organs and point towards more successful therapeutic approaches to sensory system deficits.
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