Michael H. Chase

It is well established that cholinergic agonists, when injected into the pontine reticular formation in cats, produce a generalized suppression of motor activity (1, 3, 6, 14, 18, 27, 33, 50). The responsible neuronal mechanisms were explored by measuring ventral root activity, the amplitude of the Ia-monosynaptic reflex, and the basic electrophysiological properties of hindlimb motoneurons before and after carbachol was microinjected into the pontine reticular formation of decerebrate cats. Intrapontine microinjections of carbachol (0.25-1.0 microliter, 16 mg/ml) resulted in the tonic suppression of ventral root activity and a decrease in the amplitude of the Ia-monosynaptic reflex. An analysis of intracellular records from lumbar motoneurons during the suppression of motor activity induced by carbachol revealed a considerable decrease in input resistance and membrane time constant as well as a reduction in motoneuron excitability, as evidenced by a nearly twofold increase in rheobase. Discrete inhibitory postsynaptic potentials were also observed following carbachol administration. The changes in motoneuron properties (rheobase, input resistance, and membrane time constant), as well as the development of discrete inhibitory postsynaptic potentials, indicate that spinal cord motoneurons were postsynaptically inhibited following the pontine administration of carbachol. In addition, the inhibitory processes that arose after carbachol administration in the decerebrate cat were remarkably similar to those that are present during active sleep in the chronic cat. These findings suggest that the microinjection of carbachol into the pontine reticular formation activates the same brain stem-spinal cord system that is responsible for the postsynaptic inhibition of alpha-motoneurons that occurs during active sleep.

Postsynaptic inhibition is a principal process responsible not only for the atonia of the somatic musculature during active sleep but also for the phasic episodes of decreased motoneuron excitability that accompany bursts of REMs during this state. These postsynaptic processes are dependent upon the presence of active sleep-specific IPSPs, which are apparently mediated by glycine. The phasic excitation of motoneurons during REM periods is due to excitatory postsynaptic potentials that, when present, encounter a motoneuron already subjected to enhanced postsynaptic inhibition. These EPSPs are mediated by a non-NMDA neurotransmitter. Thus, from the perspective of motoneurons, active sleep can be characterized as a state abundant in the availability of strikingly potent patterns of postsynaptic inhibition and, during REM periods, not only by enhanced postsynaptic excitation, but also by enhanced postsynaptic inhibition. The site of origin of these inhibitory and excitatory drives is, at present, less clearly defined. There is a consensus that the structure(s) from which the inhibitory drives emanate are located in the lower brainstem, with a cholinoceptive trigger zone situated in the dorsolateral pontine tegmentum in or in the vicinity of the nucleus pontis oralis. We have suggested that from this cholinoceptive trigger zone there emanates an excitatory drive that directly, or through interneurons, excites a medullary are in or in the vicinity of the nucleus reticularis gigantocellularis. Thus, a cascade of cholinoceptively activated excitatory activity proceeds to eventually activate inhibitory interneurons whose activation results in motoneuron inhibition and muscle atonia during active sleep. Resolution of the precise location and mechanisms of interaction of the supraspinal inhibitory and excitatory motoneuron control mechanism constitutes a major goal of future experiments and the next major challenge for researchers in this field.