Neural Circuits Underlying Taste Behavior

Project: Research project

Project Details

Description

Survival of all animals critically depend on their ability to incorporate nutrient substances while avoiding
poisons. Taste information is detected by epithelial taste receptor cells (TRCs) on the tongue and alate, each one dedicated to a single taste quality, and relayed by neurons in the geniculate/petrosal ganglia to the brain. The ganglia neurons are also tuned to a single taste quality, forming ‘labeled lines’: sweet TRCs signal to sweet neurons, salty to salty, bitter to bitter, etc.
Taste information from the periphery is next conveyed to the nucleus of the solitary tract (NTS) in the brainstem. Here, they integrate with other information about the ingesta (odor, texture, temperature, etc..) and the internal state of the animal. Our current understanding of the brainstem circuits is still limited to the gross anatomical ‘nucleus’ level, and specific information about molecules and cells is lacking. Here, I propose studies to uncover the assembly and function of taste-dependent circuits in the brainstem.
Aim1. Functional imaging of taste representation in the brainstem. Leveraging my expertise in in vivo calcium imaging, I propose to identify the ‘taste map’ in the NTS. Recent advances in multiphoton microscopy and ‘miniscopes’ have enabled imaging of deep brain regions that were previously inaccessible. I plan to employ these imaging technologies to observe neuronal ensembles as they respond to various taste stimuli using fluorescence from GCaMP calcium reporter as a proxy for neuronal activity. This will provide insights about the tuning properties of these neurons and how they are modulated by other sensory and/or homeostatic cues.
Aim2. Identification and functional validation of taste-specific brainstem neuron markers. Molecular
markers provide a platform for circuitry mapping and functional manipulations. I propose to identify taste-specific marker genes in the brainstem using a candidate-based approach by analyzing abundant expression data (e.g. Allen Brain Atlas). As an alternative approach, we will perform activity-dependent labeling of NTS neurons in TRAP2 mice after tastant presentation, followed by single cell RNA-sequencing to identify enriched gene transcripts. With these candidate gene(s), we will engineer mice to drive GCaMP expression, and measure cell population-specific responses to taste stimuli by in vivo fiber photometry. For example, ‘bitter neurons’ in the NTS should only respond while the animal is presented with bitter stimuli. In preparation for this grant, I have accumulated considerable preliminary data with viable candidate markers for bitter-specific neurons. Subsequently, optogenetic and chemogenetic approaches will be employed to test whether NTS neurons marked by candidate marker(s) mediate aversion/attraction behaviors.
Aim3. To map and manipulate taste-evoked behaviors. The experiments described above are expected to identify cellular substrates for taste ‘sensation’ in the NTS and provide entry points to probe relevant behavioral circuits in other regions of the brainstem. For example, how are sour tastes able to evoke immediate salivation? Notably, decerebrate animals maintain taste-specific orofacial motor (chewing, retching) and salivary responses, suggesting that connections between taste and these ‘reflex’ circuits are hardwired in the brainstem. I will map circuits between NTS taste neurons and other brainstem centers using viral tracing techniques (e.g. monosynaptically-restricted rabies viruses). The second-order neurons labeled by this method will be subjected to optogenetic m
StatusActive
Effective start/end date4/1/203/31/23

Funding

  • Whitehall Foundation, Inc. (2019-12-41)

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