Biology subjects

Zimmerman, A. D.

Publications and source records attributed to Zimmerman, A. D..

3 recordsLinked to original sources

bioRxiv2021

An N-terminal Fusion Allele to Study Melanin Concentrating Hormone Receptor 1

Cilia on neurons play critical roles in both the development and function of the central nervous system (CNS). While it remains challenging to elucidate the precise roles for neuronal cilia, it is clear that a subset of G-protein-coupled receptors (GPCRs) preferentially localize to the cilia membrane. Further, ciliary GPCR signaling has been implicated in regulating a variety of behaviors. Melanin concentrating hormone receptor 1 (MCHR1), is a GPCR expressed centrally in rodents known to be enriched in cilia. Here we have used MCHR1 as a model ciliary GPCR to develop a strategy to fluorescently tag receptors expressed from the endogenous locus in vivo. Using CRISPR/Cas9, we inserted the coding sequence of the fluorescent protein mCherry into the N-terminus of Mchr1. Analysis of the fusion protein (mCherryMCHR1) revealed its localization to neuronal cilia in the CNS, across multiple developmental time points and in various regions of the adult brain. Our approach simultaneously produced fortuitous in/dels altering the Mchr1 start codon resulting in a new MCHR1 knockout line. Functional studies using electrophysiology show a significant alteration of synaptic strength in MCHR1 knockout mice. A reduction in strength is also detected in mice homozygous for the mCherry insertion, suggesting that while the strategy is useful for monitoring the receptor, activity could be altered. However, both lines should aid in studies of MCHR1 function and contribute to our understanding of MCHR1 signaling in the brain. Additionally, this approach could be expanded to aid in the study of other ciliary GPCRs.

neuroscience↗

bioRxiv2020

Sensory neurons expressing the atypical olfactory receptor guanylyl cyclase D are required for the acquisition of odor preferences by mice in diverse social contexts

Animals use social communication to learn important information from conspecifics that can guide appropriate behavioral choices. For example, during the social transmission of food preference (STFP), conspecific semiochemicals detected by mouse olfactory sensory neurons (OSNs) expressing the atypical olfactory receptor guanylyl cyclase D (GC-D+ OSNs) promote the acquisition of food preferences in the recipient animal, mitigating the risk of ingesting food contaminated with toxins or pathogens. However, it is unclear if GC-D+ OSNs mediate preference learning outside this specific context. Here, we report that GC-D+ OSNs are required for the acquisition of odor preferences by both adult and juvenile mice, and that GC-D-dependent preference could be formed for conditionally aversive odors. We used a two-choice olfactory behavioral test to assess odor preferences in adult Gucy2d +/+, +/- and -/- mice that encountered novel odors together with GC-D+ OSN stimuli (guanylin family peptides), during social investigation of a live conspecific, or during suckling as pups. Gucy2d +/+ and +/-mice (which express functional GC-D), but not Gucy2d -/- littermates, successfully acquire a preference for the demonstrated odor in any of these behavioral paradigms. Mice could even acquire a GC-D-dependent preference for odors to which they had recently formed a conditioned aversion. Together, these results demonstrate that GC-D+ OSNs mediate the acquisition of socially-transmitted odor preferences in different social and experiential contexts and at different life stages.

animal behavior and cognition↗

bioRxiv2018

Unique molecular markers for GC-D-expressing olfactory sensory neurons and chemosensory neurons of the Grueneberg ganglion

The main olfactory bulb (MOB) is differentiated into subregions based on their innervation by molecularly distinct chemosensory neurons. For example, olfactory sensory neurons (OSNs) that employ a cGMP-mediated transduction cascade - guanylyl-cyclase D-expressing (GC-D+) OSNs of the main olfactory epithelium (MOE) and chemosensory neurons of the Grueneberg ganglion (GGNs) - project to distinct groups of \"necklace\" glomeruli encircling the caudal MOB. To better understand the unique functionality and neural circuitry of the necklace glomeruli and their associated sensory neurons, we sought to identify additional molecular markers that would differentiate GC-D+ OSNs and GGNs as well as their target glomeruli. We found in mouse that GC-D+ OSNs, but not other MOE OSNs or GGNs, express the neuropeptide CART (cocaine- and amphetamine-regulated transcript). Both GC-D+ OSNs and GGNs, but not other MOE OSNs, express the Ca2+/calmodulin-dependent phosphodiesterase Pde1a, which is immunolocalized throughout the dendrites, somata and axons of these neurons. Stronger Pde1a immunolabeling in necklace glomeruli innervated by GGNs than in those innervated by GC-D+ OSNs suggests either greater Pde1a expression in individual GGNs than in GC-D+ OSNs or a difference in sensory neuron innervation density between the two types of necklace glomeruli. Together, the unique molecular signatures of GC-D+ OSNs, GGNs and their MOB targets offer important tools for understanding the processing of chemosensory information by olfactory subsystems associated with the necklace glomeruli.

neuroscience↗