Abstracts

Rationale: The cell-type specific transgenic technique has been extensively used to uncover the pathogenic mechanism of genetic epilepsy. The Emx1-IRES-Cre mouse is frequently used to target gene recombination in forebrain excitatory neurons.  However, previous studies have reported that Emx1-Cre is significantly expressed during development in peripheral autonomic ganglia, hence mediates recombination in these cells as well when crossed with a floxed line.  The functional significance of peripheral Emx1-Cre+ cells to epilepsy-related phenotype is currently not well understood.

Methods: We examined anatomical Emx1-Cre expression in cervical autonomic ganglia of adult mice and optogenetically tested their physiological function by crossing them with a tdtomato fluorescent reporter (Emx1-tdtomato) or a channelrhodopsin line (Emx1-ChR2). 

Results: We identified significant expression of Emx1-Cre⁺ cells located in the cells within the nodose ganglion as well as projection nerve fibers in the carotid sinus and superior cervical ganglion.  In agreement, fluorescent Emx1-tdtomato signals were detected centrally within the afferent vagus nerve fibers which terminate in the dorsal medulla, especially in the nucleus tractus solitarius (NTS) and part of the neighboring trigeminal nucleus.  Photostimulation of the NTS fiber field reliably evoked EPSCs in the NTS neurons in vitro.  In addition, photostimulation of the dorsal medulla surface covering the NTS, vagus nerve, and the carotid sinus in vivo modulated the heart rate and respiratory rate in urethane anesthetized Emx1-ChR2 mice.    

Conclusions: These results confirmed Emx1-Cre expression in the peripheral autonomic system of the adult mouse.  Emx1-Cre dependent genetic recombination may affect the autonomic cardiorespiratory function if the targeted genes are expressed in these peripheral structures.

Funding: American Heart Association, The Blue Bird Circle