Department of Physiology and the Brain Research Institute
UCLA, School of Medicine, Los Angeles, CA 90024
hen an animal switches between behavioral states, such as from quiet sleep to REM sleep, and from active sleep to wakefulness, there are profound changes in almost all physiological systems. These changes occur rapidly, with an observable time base of seconds, although the responsible mechanisms are likely operating in the range of milliseconds. We are exploring the processes that allow an animal to switch from one behavioral state to another by examining a prototypical physiological characteristic of REM sleep, which is motor atonia. As a basis for exploring these processes, we are investigating the fashion in which non-NMDA-mediated EPSPs occur spontaneously in motoneurons during wakefulness, and at the moment of REM sleep and for its duration, there arise glycinergically-mediated IPSPs.
How can these patterns of motor response-reversal take place with the only variable being the change of state of the animal? Our hypothesis is that at the moment of REM sleep (and for the duration of the state), a switching mechanism (or neuronal gate) is activated in the nucleus pontis oralis so that input to this region, that normally triggers motor excitation, now results in motor inhibition. The proposed neuronal gating mechanism that operates during active sleep is based upon the cholinergic activation of cells in the nucleus pontis oralis, the cholinergic inhibition of other cells in the nucleus pontis oralis and the disfacilitation of GABAergic interneurons. We further suggest that within the nucleus pontis oralis, and at each of the key relays along the active sleep-dependent motor inhibition system (i.e., the nucleus pontis oralis, a medullary motor inhibitory area and motor nuclei), activity is enhanced by the action of neuromodulators. The final result is the excitation of glycinergic terminals that promote the postsynaptic inhibition of motoneurons exclusively during active sleep.
We expect that neuromodulated neuronal gates (or switching mechanisms) are the key elements which channel activity in different directions, such as to motor inhibition during REM sleep. It is also possible that these processes of neuromodulation are also responsible for switching between the behavioral states of sleep and wakefulness by activating specific circuits which determine the behavioral state of the animal; accordingly, the coordinated switching of many neuromodulated physiological processes may determine, i.e., define, the ongoing behavioral state. In general, processes of neuromodulation may be viewed as a method that the nervous system employs to enact great changes in physiological processes by activating critical neuronal junctions. Thus, a small expenditure of "neuronal energy", perhaps only a few molecules, may be necessary to open or close neuronal switches that control profoundly different behavioral states.
