Homosynaptic depression and transmitter turnover in spinal monosynaptic pathway

1. The transmission in the spinal monosynaptic pathway was studied during repetitive stimulation of a motor nerve by 10 stimuli at 2, 5, or 10 Hz in spinal cats. Initially, the amplitudes of the monosynaptic responses rapidly declined, reaching a plateau after a few stimuli. The level of the plateau was inversely related to the frequency of stimulation. 2. This depression of monosynaptic response was seen only when the same pathway was stimulated; the response elicited from the lateral gastrocnemius was not depressed when preceded by stimulation of the medial gastrocnemius nerve and vice versa. Pretreatment with semicarbazide left the homosynaptic depression unchanged while suppressing the dorsal root reflex. The participation of a depolarization of primary afferents in the described depression is, therefore, unlikely. 3. The decrease of transmitter release by successive volleys, which is the cause of the observed depression, could conceivably be related to the depletion of transmitter stores. 4. A procedure is described, based on this assumption, which allows the calculation of transmitter turnover. The input-output relation in the spinal monosynaptic pathway is used to convert the amplitudes of monosynaptic responses to the amounts of transmitter, both relative to the maximum response. The changes of transmitter release are analyzed under the assumption that each volley releases instantaneously a constant fraction of the transmitter store available for release and that this store is replenished at a constant fraction of the depleted part per second. 5. The values of fractional release per volley were about 0.4, irrespective of frequency of stimulation. 6. The values of fractional replenishment per second ranged from about 1 to 5 on the average, depending directly on the frequency of stimulation. 7. It is suggested that the described procedure might be useful in analyzing drug effects on synaptic transmission.