Electrophysiological Properties of Rostral Ventrolateral Medulla Presympathetic Neurons Modulated by the Respiratory Network in Rats

Davi J. A. Moraes, Melina P. da Silva, Leni G. H. Bonagamba, Andre´ S. Mecawi, Daniel B. Zoccal,

Jose´ Antunes-Rodrigues, Wamberto A. Varanda, and Benedito H. Machado.  Electrophysiological Properties of Rostral Ventrolateral Medulla Presympathetic Neurons Modulated by the Respiratory Network in Rats J. Neurosci 33: 19223–19237,2013.

This paper from Benedito Machado’s group in Brazil examined RVLM presympathetic neurons and attempted to better characterize the mechanisms of respiratory related sympathetic activity also known as respiratory-sympathetic coupling.  Although it exists in most sympathetic nerve recordings, respiratory-sympathetic coupling is most easily observed when one examines both sympathetic nerve activity and phrenic nerve activity, the latter being the motor nerve that innervates the diaphragm and drives breathing.  It has been suggested that this coupling occurs at the level of the individual, spinally projecting C1 and non-C1 neuron. 

These investigators achieved this by using the in situ working heart-brainstem preparation, which has been referred to as the “half rat” preparation.  Although neither considered in vivo nor a fully intact animal, the preparation does allow the use of whole-cell patch recordings in the absence of anesthesia because the animal is decerebrated, which means the areas of the brain that perceive pain are removed.  In addition to the electrophysiology they are able to fill the recorded cells with biocytin and identify them with immunohistofluorence and stain for TH to determine if they are TH positive or not.  After recording from the cells they are able obtain the RNA from them and do single cell PCR.  In addition to being a real technical tour de force they also examine normal rats and rats that have been submitted to chronic intermittent hypoxia (CIH), a common model for sleep apnea.

The authors found that both C1 and non C1 neurons expressed several different kinds of phenotypes based on intrinsic electrophysiological properties, whether or not they had respiratory synaptic inputs, and what ionic currents they expressed.  Interestingly in this preparation all RVLM neurons had persistent sodium current-dependent pacemaker properties that persisted after synaptic blockade.  These latter data support the notion that RVLM neurons are capable of generating their own firing which could be important in states of overactivity including hypertension, heart failure and inactivity.  Also non-C1 but not C1 neurons from animals that had been exposed to CIH demonstrated enhanced excitatory input which could explain why CIH animals exhibit increased sympathetic nerve activity.

~PJM