Effect of orexin-B-saporin-induced lesions of the lateral hypothalamus on performance on a progressive ratio schedule

It has been suggested that a sub-population of orexinergic neurones whose somata lie in the lateral hypothalamic area (LHA) play an important role in regulating the reinforcing value of both food and drugs. This experiment examined the effect of disruption of orexinergic mechanisms in the LHA on performance on the progressive-ratio schedule of reinforcement, in which the response requirement increases progressively for successive reinforcers. The data were analysed using a mathematical model which yields a quantitative index of reinforcer value and dissociates effects of interventions on motor and motivational processes (Killeen, 1994). Rats were trained under a progressive-ratio schedule using food-pellet reinforcement. They received bilateral injections of conjugated orexin-B-saporin (OxSap) into the LHA or sham lesions. Training continued for a further 40 sessions after surgery. Equations were fitted to the response rate data from each rat, and the parameters of the model were derived for successive blocks of 10 sessions. The OxSap lesion reduced the number of orexin-containing neurones in the LHA by approximately 50% compared to the sham-lesioned group. The parameter expressing the incentive value of the reinforcer was not significantly altered by the lesion. However, the parameter related to the maximum response rate was significantly affected, suggesting that that motor capacity was diminished in the OxSap-lesioned group. The results indicate that OxSap lesions of the LHA disrupted food-reinforced responding on the progressive-ratio schedule. It is suggested that this disruption was brought about by a change in non-motivational (motor) processes

Cessation of activity in red nucleus neurons during stimulation of the medial medulla in decerebrate rats

The pontine oral reticular nucleus, gigantocellular reticular nucleus (Gi) and dorsal paragigantocellular nucleus (DPGi) of the medulla are key elements of a brainstem-reticulospinal inhibitory system that participates in rapid eye movement (REM) sleep atonia. Our recent study has shown that excitation of these brainstem nuclei in decerebrate rats inhibits locus coeruleus cells and the midbrain locomotor region neurons related to muscle tone facilitation. In the present study we have examined the influences of electrical and chemical stimulation of Gi and DPGi inhibitory sites on the activity of neurons located in the magnocellular part of the red nucleus (RMC), a cell group that participates in both the tonic and phasic regulation of motor output. A total of 192 RMC neurons were recorded in precollicular-premammillary decerebrate rats with muscle rigidity and induced locomotion. Thirty-three RMC neurons were identified antidromically as rubrospinal (RMC-spinal) cells by stimulation of the contralateral dorsolateral funiculus at the L2 level. A total of 141 RMC neurons (88.7 %) and all RMC-spinal neurons were inhibited during electrical stimulation of Gi and DPGi inhibitory sites. This cessation of activity was correlated with bilateral muscle atonia or blockage of locomotion. Six RMC cells (3.8 %) were excited (224 ± 50 %, n = 6, minimum = 98, maximum = 410, P < 0.05) and 11 cells (7 %) gave no response to Gi and DPGi stimulation. Microinjections of kainic acid (100 μm, 0.2 μl) into Gi and DPGi inhibitory sites, previously identified by electrical stimulation, produced a short-latency (35 ± 3.5 s, n = 11) decrease of rigid hindlimb muscle tone and inhibition of all tested RMC (n = 7) and RMC-spinal (n = 5) neurons. These results, combined with our recent published data, suggest that inhibition of motor function during activation of the brainstem inhibitory system is related to both the descending inhibition of spinal motoneurons and suppression of activity in supraspinal motor facilitatory systems. These two mechanisms acting synergistically may cause generalized motor inhibition during REM sleep and cataplexy