Integrative responses of neurons in parabrachial nuclei to a nauseogenic gastrointestinal stimulus and vestibular stimulation in vertical planes

Abstract

In addition, the PBN/KF region receives inputs from the vestibular system and likely mediates the malaise associated with motion sickness. However, previous studies have not considered whether GI and vestibular inputs converge on the same PBN/KF neurons, and if so, whether the GI signals alter the responses of the cells to body motion. The present study, conducted in decerebrate cats, tested the hypothesis that intragastric injection of copper sulfate, which elicits emesis by irritating the stomach lining, modifies the sensitivity of PBN/KF neurons to vertical plane rotations that activate vestibular receptors. Intragastric copper sulfate produced a 70% median change in the gain of responses to vertical plane rotations of PBN/KF units, whose firing rate was modified by the administration of the compound; the response gains for 16 units increased and those for 17 units decreased. The effects were often dramatic: out of 51 neurons tested, 13 responded to the rotations only after copper sulfate was injected, whereas 10 others responded only before drug delivery. These data show that a subset of PBN/KF neurons, whose activity is altered by a nauseogenic stimulus also respond to body motion and that irritation of the stomach lining can either cause an amplification or reduction in the sensitivity of the units to vestibular inputs. The findings imply that nausea and affective responses to vestibular stimuli may be modified by the presence of emetic signals from the GI system.

Responses of neurons in the caudal medullary lateral tegmental field to visceral inputs and vestibular stimulation in vertical planes

“…Data were collected from 15 purpose-bred adult male cats (Liberty Research, Waverly, NY), weighing 4 -5 kg (medianϭ4.4 kg). Because the procedures employed in this study were similar to those described in two recent articles (53,54), they are presented in abbreviated fashion below.…”

“…Surgery was performed under 1-3% isoflurane anesthesia to cannulate both femoral veins, insert a Millar (Houston, TX) blood pressure transducer through the femoral artery into the abdominal aorta, perform a tracheostomy, and ligate both carotid arteries. The carotid arteries were also dissected free of surrounding tissues and prepared for mechanical stretch of the carotid sinus, as in our prior studies (15,53,54). An intragastric catheter was inserted through an esophagostomy to administer copper sulfate (53,54).…”

“…The carotid arteries were also dissected free of surrounding tissues and prepared for mechanical stretch of the carotid sinus, as in our prior studies (15,53,54). An intragastric catheter was inserted through an esophagostomy to administer copper sulfate (53,54). Subsequently, the animal was placed in a stereotaxic frame with the head pitched-down 30°to vertically align the vertical semicircular canals, and the body was secured using hip pins and a clamp placed on the dorsal process of the T1 vertebra.…”

“…Electrode penetrations were made using 4 -6 M⍀ tungsten microelectrodes (FHC, Bowdoin, ME), from 8.5-12 mm posterior to stereotaxic zero and 2-5 mm lateral to the midline, to record activity from LTF neurons. Single-unit activity, blood pressure, and tilt table position were sampled using a Micro1401-2 data collection system and Spike2 version 6 software (Cambridge Electronic Design, Cambridge, UK), as discussed in our previous papers (15,53,54). In addition, the electrocardiogram was recorded using leads placed on each side of the chest and sampled at 1,000 Hz.…”

“…Our previous study showed that the delivery of the emetic drug copper sulfate to the stomach altered the gain of responses of parabrachial nucleus neurons to vestibular stimulation (54). Because the parabrachial nuclei play a key role in relaying visceral inputs to the diencephalon and telencephalon (14), parabrachial neurons with labyrinthine inputs likely participate in generating affective responses and queasiness during motion sickness and related conditions (5).…”