Session: 610 APS Central Regulation of Autonomic Control: CNS Poster Session
(610.5) Gastrointestinal mechanosensation affects the activity of prefrontal cortical neurons mediating social behavior in mice
Sunday, April 3, 2022
10:15 AM – 12:15 PM
Location: Exhibit/Poster Hall A-B - Pennsylvania Convention Center
Poster Board Number: E556
Jesus Penaloza Aponte (University of Florida, University of Florida), Karen Scott (University of Florida, University of Florida), Dominique Johnson (University of Florida, University of Florida), Caeley Reever (University of Florida), Justin Smith (University of Florida, University of Florida), Guillaume de Lartigue (University of Florida, University of Florida), Annette de Kloet (University of Florida, University of Florida), Eric Krause (University of Florida, University of Florida, University of Florida, University of Florida)
Presenting Author University of Florida, University of Florida
Social cognition requires integration of sensory modalities with emotion and experience to plan and engage in appropriate social behavior. Oxytocin is a neuropeptide that shapes the perception of social stimuli by activating the oxytocin receptor (Oxtr). Neurons within the medial prefrontal cortex (mPFC) that express Oxtr(s) (referred to as mPFCOxtr) integrate these complex systems. Oxytocin acts within the brain to influence the perception of the external environment; however, Oxtr(s) are also expressed on vagal sensory afferents, suggesting that oxytocin may also influence interoception or the ability to sense one’s internal state. To better understand the role of interoception in social cognition, we examined the structure and function of the neurons within the nodose ganglia that express the Oxtr (referred to as NDGOxtr). To visualize NDGOxtr, we bilaterally injected Cre-inducible adeno-associated virus (AAV) synthesizing mCherry or tdTomato into the nodose ganglia (NDG) of mice with Cre-recombinase directed to the Oxtr gene (Oxtr-Cre mice). We found that NDGOxtr expressed mRNAs for the mechanically gated ion channels, Piezo 1/2, and sent fibers to the stomach and duodenum that formed intramuscular arrays or intraganglionic laminar endings. These results suggest that NDGOxtr function as mechanoreceptors that detect distention of the gastrointestinal tract. Next, we used in vivo Ca2+ imaging to determine the effect that gastric distention has on mPFCOxtr that mediate social behavior. Oxtr-Cre mice were delivered Cre-inducible AAV expressing the fluorescent Ca2+ indicator, GCaMPf, into the mPFC, and subsequently, implanted with a GRIN lens. After habituation to the head mounted miniscope, mice were tested in the social interaction paradigm and Ca2+ events were recorded. Receiver operating characteristic analysis revealed that ≈30% of mPFCOxtr couple firing to social interaction. Next, we evaluated how gastric distention may influence the activity of mPFCOxtr. Mice were given a sham gavage or a gavage of methylcellulose and Ca2+ events from mPFCOxtr were recorded. Differences in Ca2+ events were calculated using a Wilcoxon rank sum test to the classify individual neurons as inhibited, excited, or unchanged by the stimulus. Intriguingly, gavage of methylcellulose robustly inhibited mPFCOxtr relative to the sham-treated control. To determine whether NDGOxtr mediate this inhibition, Oxtr-Cre mice outfitted for in vivo Ca2+ imaging were given Cre-inducible AAV expressing channelrhodopsin2 into the NDG and a fiber optic was implanted into the nucleus of the solitary tract (NTS). This approach enables optogenetic excitation of axons in the NTS originating from NDGOxtr during simultaneous Ca2+ imaging of mPFCOxtr. Preliminary results indicate that optogenetic excitation of NDGOxtr also inhibit mPFCOxtr. Collectively, our results suggest that mechanosensation of the gastrointestinal tract may have a profound influence over the perception of social stimuli.
