Learning And Memory In Central Contral Of Respiratory Rhythm

Learning and memory are important computational strategies of the brain. They are generally believed to result from changes in synaptic efficacy induced by afferent activity. Non-associative learning that includes habituation and desensitization classically, and associative learning that is conditioning reflex, are the two major forms of learning. Memory can be divided into short-term memory and long-term memory. Synaptic plasticity that can be both structural and functional is the physiological basis of learning and memory. Recently, such sophisticated cognitive functions of the high brain have been found to be possibly existing in the brainstem and spinal cord.Although there are proofs that the brainstem respiratory neuronal circuit has the ability of learning and memory, this problem still needs to be experimentally addressed. In the present study, three parts of experiments were performed. First, we re-examined the inspiratory inhibition of Botzinger complex (Bot C) to see if it showed signs of nonassociative learning. At the same time, the influence of 5-HTergic raphe pallidus (RP) and the NEergic locus coeruleus (LC) on the Bot.C's inspiratory inhibition were observed. Second, we studied the effects of NO on the long-term respiratory facilitation produced by repeated electrical stimulation of nucleus raphe obscurus (NRO). Finally, we studied the learning and memory exhibited by the classic Hering-Breuer reflex.1. Inspiratory inhibition of Bot.C and modulation by RP and LCBot.C is a group of expiratory neurons in the rostral ventral respiratory group of the medulla. It plays an important role in respiratory phase transition andin the formation of expiratory phase. Sustained long time electrical stimulation (10-50 uA, 40-100 Hz, 0.1 msec, for 15-30 sec) of Bot.C in rabbit caused the inhibition of phrenic nerve discharge, which showed intensity and frequency dependence. Habituation was shown during the stimulation, showing the inspiratory inhibition decreased gradually. Post-stimulus rebound exhibited upon the cessation of the stimulation, showing the magnitude of the phrenic activity increased transiently and returned gradually to the baseline. Habituation of the inhibition during the stimulation was frequency and intensity dependent inversely, showing that the degree of habituation was weakened with the increase of the stimulus intensity and frequency, but the degree of post-stimulus rebound was enhanced. Short-term memory was shown in the inhibition and habituation of the phrenic activity, showing the inhibitory response of the second stimulation was weaker when the intermission period between the two consecutive stimulation was shorter, but when the intermission was increased to 30 sec, the inhibition of the second stimulation was not significantly different from the first one (P>0.05).Electrical stimulation of RP or LC depressed the inspiratory inhibition caused by electrical stimulation of Bot.C. After giving long train stimulation to the RP or LC, within a short period of time (2-20 sec), another long train stimulation to the Bot.C caused weaker inspiratory inhibition, stronger habituation and stronger post-stimulus rebound than that of pure Bot.C's stimulation. Such modulation showed short-term memory, which typically lasted 18-20 sec. Microinjection of glutamate into the RP or LC mimicked the effects of sustained long time electrical stimulation on the Bot.C's inspiratory inhibition.2. Effects of L-Arginine on LTF of phrenic activity induced by sustained electrical stimulation of nucleus raphe obscurusSustained long time (5 min) electrical stimulation of nucleus raphe obscurus (NRO) caused long-term facilitation (LTF) of the phrenic nerve discharge, showing significant increases in both integrated phrenic activity and respiratory frequency lasting 35±5 min (n=15) after cessation of the stimulus. Microinjection of L-Arg into NRO did not produce significant changes in phrenic discharge (n=10, P>0.05), comparing with the control. After microinjection, 5-minutes sustained stimulation of NRO lengthened the duration of the long-term facilitation to 55±5 min (n=10, PO.01).