Error signals as powerful stimuli for the operant conditioning-like process of the fictive respiratory output in a brainstem-spinal cord preparation from rats.

Respiratory neuromuscular activity needs to adapt to physiologic and pathologic conditions. We studied the conditioning effects of sensory fiber (putative Ia and II type from neuromuscular spindles) stimulation on the fictive respiratory output to the diaphragm, recorded from C4 phrenic ventral root, of in-vitro brainstem-spinal cord preparations from rats. The respiratory burst frequency in these preparations decreased gradually (from 0.26±0.02 to 0.09±0.003 bursts(-1)±SEM) as the age of the donor rats increased from zero to 4 days. The frequency greatly increased when the pH of the bath was lowered, and was significantly reduced by amiloride. C4 low threshold, sensory fiber stimulation, mimicking a stretched muscle, induced a short-term facilitation of the phrenic output increasing burst amplitude and frequency. When the same stimulus was applied contingently on the motor bursts, in an operant conditioning paradigm (a 500ms pulse train with a delay of 700ms from the beginning of the burst) a strong and persistent (>1h) increase in burst frequency was observed (from 0.10±0.007 to 0.20±0.018 bursts(-1)). Conversely, with random stimulation burst frequency increased only slightly and declined again within minutes to control levels after stopping stimulation. A forward model is assumed to interpret the data, and the notion of error signal, i.e. the sensory fiber activation indicating an unexpected stretched muscle, is re-considered in terms of the reward/punishment value. The signal, gaining hedonic value, is reviewed as a powerful unconditioned stimulus suitable in establishing a long-term operant conditioning-like process.