Selectively Labeling and Distinguishing Adrenergic and Noradrenergic Neurons in the Sympathetic Nervous System

The sympathetic nervous system, with adrenaline and noradrenaline as key neurotransmitters, plays a vital role in regulating physiological functions. However, distinguishing between adrenergic and noradrenergic neurons has been challenging. This study used CRISPR/Cas9 technology to generate Net-Cre and Pnmt-p2a-Cre transgenic mouse lines. The results showed that gene editing did not affect the normal reproduction and development of these mice, and their stress levels were comparable to those of wild-type mice. In the central nervous system (CNS), noradrenergic neurons are distributed mainly in the brainstem and other regions, whereas adrenergic neurons are distributed specifically in the ventrolateral medulla (VLM) and the nucleus of the solitary tract (NTS). In the peripheral nervous system (PNS), more than 98% of neurons in the sympathetic ganglia are noradrenergic. AAV-based tracing of the locus coeruleus (LC) revealed that LC noradrenaline transporter (NET) neurons had extensive long-distance projections, whereas phenylethanolamine-N-methyltransferase (PNMT) neurons had short-range projections. These transgenic mouse lines provide a powerful tool for further research on the functions of adrenergic and noradrenergic neurons and the sympathetic nervous system.