Almost every part of the brain connects either directly or indirectly with every other part, which creates a serious challenge. If the first part excites the second, the second the third, the third the fourth, and so on until finally the signal re-excites the first part, it is clear that an excitatory signal entering any part of the brain would set off a continuous cycle of re-excitation of all parts. If this cycle should occur, the brain would be inundated by a mass of uncontrolled reverberating signals—signals that would be transmitting no information but, nevertheless, would be consuming the circuits of the brain so that none of the informational signals could be transmitted. Such an effect occurs in widespread areas of the brain during epileptic seizures. How does the central nervous system prevent this effect from happening all the time? The answer lies mainly in two basic mechanisms that function throughout the central nervous system: (1) inhibitory circuits and (2) fatigue of synapses.
INHIBITORY CIRCUITS AS A MECHANISM FOR STABILIZING NERVOUS SYSTEM FUNCTION
Two types of inhibitory circuits in widespread areas of the brain help prevent excessive spread of signals: (1) inhibitory feedback circuits that return from the termini of pathways back to the initial excitatory neurons of the same pathways (these circuits occur in virtually all sensory nervous pathways and inhibit either the input neurons or the intermediate neurons in the sensory pathway when the termini become overly excited), and (2) some neuronal pools that exert gross inhibitory control over widespread areas of the brain (for instance, many of the basal ganglia exert inhibitory influences throughout the muscle control system).
SYNAPTIC FATIGUE AS A MEANS OF STABILIZING THE NERVOUS SYSTEM
Synaptic fatigue means simply that synaptic transmission becomes progressively weaker the more prolonged and more intense the period of excitation. Figure 1 shows three successive records of a flexor reflex elicited in an animal caused by inflicting pain in the footpad of the paw. Note in each record that the strength of contraction progressively “decrements”—that is, its strength diminishes; much of this effect is caused by fatigue of synapses in the flexor reflex circuit. Furthermore, the shorter the interval between successive flexor reflexes, the less the intensity of the subsequent reflex response.
Fig1. Successive flexor reflexes showing fatigue of conduction through the reflex pathway.
Automatic Short-Term Adjustment of Pathway Sensitivity by the Fatigue Mechanism. Now let us apply this phenomenon of fatigue to other pathways in the brain. Those that are overused usually become fatigued, so their sensitivities decrease. Conversely, those that are underused become rested and their sensitivities increase. Thus, fatigue and recovery from fatigue constitute an important short term means of moderating the sensitivities of the different nervous system circuits. These functions help to keep the circuits operating in a range of sensitivity that allows effective function.
Long-Term Changes in Synaptic Sensitivity Caused by Automatic Down-Regulation or Up-Regulation of Synaptic Receptors. The long-term sensitivities of syn apses can be changed tremendously by upregulating the number of receptor proteins at the synaptic sites when there is underactivity and downregulating the receptors when there is overactivity. The mechanism for this process is the following: Receptor proteins are being formed constantly by the endoplasmic reticular–Golgi apparatus system and are constantly being inserted into the receptor neuron synaptic membrane. However, when the synapses are overused so that excesses of transmitter substance combine with the receptor proteins, many of these receptors are inactivated and removed from the synaptic membrane.
It is indeed fortunate that upregulation and down regulation of receptors, as well as other control mechanisms for adjusting synaptic sensitivity, continually adjust the sensitivity in each circuit to almost the exact level required for proper function. Think for a moment how serious it would be if the sensitivities of only a few of these circuits were abnormally high; one might then expect almost continual muscle cramps, seizures, psychotic disturbances, hallucinations, mental tension, or other nervous disorders. Fortunately, the automatic controls normally readjust the sensitivities of the circuits back to controllable ranges of reactivity any time the circuits begin to be too active or too depressed.
