Somatostatin selectively ablates post-inspiratory activity after injection into the Bötzinger complex.
Somatostatin (SST) neurons in the ventral respiratory column (VRC) are essential for the generation of normal breathing. Little is known about the neuromodulatory role of SST on ventral respiratory neurons other than that local administration induces apnoea. Here, we describe the cardiorespiratory effects of microinjecting SST into the preBötzinger and Bötzinger complexes which together elaborate a normal inspiratory augmenting and expiratory respiratory pattern, and on spinally projecting respiratory subnuclei (rostral ventral respiratory group; rVRG). Microinjections (20-50 nl) of SST (0.15, 0.45, 1.5 mM) were made into respiratory subnuclei of urethane-anaesthetized, paralysed, vagotomized and artificially ventilated Sprague-Dawley rats (n=46). Unilateral microinjection of SST into the Bötzinger complex converted the augmenting activity of phrenic nerve discharge into a square-wave apneustic pattern associated with a lengthening of inspiratory period and shortening of expiratory time. Following bilateral microinjection the apneusis became pronounced and was associated with a dramatic variability in inspiratory duration. Microinjection of SST into the Bötzinger complex also abolished the post-inspiratory (post-I) motor activity normally observed in vagal and sympathetic nerves. In the preBötzinger complex SST caused bradypnoea and with increasing dose, apnoea. In the rVRG SST reduced phrenic nerve amplitude, eventually causing apnoea. In conclusion, SST powerfully inhibits respiratory neurons throughout the VRC. Of particular interest is the finding that chemical inhibition of the Bötzinger complex with SST ablates the post-I activity that is normally seen in respiratory activity and leads to apneusis. This loss of post-I activity is a unique feature of inhibition with SST and is not seen following inhibition with other agents such as galanin, GABA and endomorphin. The effect seen on post-I activity is similar to the effect of inhibiting the Kölliker-Fuse nucleus in the pons. The mechanism by which SST exerts this effect on Bötzinger neurons remains to be determined.
Australian School of Advanced Medicine, 3 Innovation Road, Macquarie University, NSW 2109, Australia.
P G R
PG
Burke
S B G
SB
Abbott
S
S
McMullan
A K
AK
Goodchild
P M
PM
Pilowsky
D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010507:Periodicity; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012125:Respiratory Center / Q000187:drug effects / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology / Q000502:physiology*
D013004:Somatostatin