INVITRO STUDIES OF PROLONGED SYNAPTIC DEPRESSION IN THE NEONATAL RAT SPINAL-CORD

1. Synaptic transmission between dorsal root afferents and alpha-motoneurones was studied in the in vitro hemisected spinal cord preparation isolated from neonatal rats. 2. Repetitive stimulation of the dorsal roots depressed the monosynaptic reflex recorded from the homologous ventral roots. The depression developed within the first five to six pulses in a stimulus train and stabilized at a plateau-like level for many seconds of stimulation. 3. The magnitude of the reflex depression depended on the stimulation interval and was capable of reducing the reflex to 17% of its undepressed control during 5 Hz stimulus trains. Complete recovery from depression was obtained at stimulation intervals greater-than-or-equal-to 30 s. 4. Monosynaptic excitatory postsynaptic potentials (EPSPs) were recorded intracellularly after reduction of the activity in polysynaptic pathways by addition of mephenesin to the bathing media. These EPSPs exhibited a prolonged, frequency-dependent synaptic depression. The depression reduced the amplitude of the EPSP to 25% of the undepressed control during 5 Hz stimulus trains, and was alleviated completely at stimulus interval greater-than-or-equal-to 60 s. 5. The prolonged EPSP depression was not altered by blockade of glycinergic and type-A gamma-aminobutyric acid (GABA(A)-ergic) receptors underlying postsynaptic inhibition in the spinal cord. Injection of current steps to motoneurones before and during the prolonged depression revealed similar values of the membrane time constant and input resistance. These excluded changes in the passive properties of the motoneurone membrane as an explanation for the observed synaptic depression. 6. Extracellular recordings of terminal potentials and their accompanying synaptic fields from motor nuclei in the ventrolateral cord revealed that the frequency-dependent depression in the synaptic fields was not preceded by any detectable changes in the amplitude or the shape of the terminal potential, suggesting that the depression cannot be attributed to impairment of action potential invasion to the afferent terminals. 7. Reduction of the basic level of transmitter release in the spinal cord by increasing the Mg2+/Ca2+ ratio of the bathing solution or by application of 2-mu-M of L(-)baclofen markedly diminished the synaptic potential depression at all the stimulation intervals tested in this study. Recovery from depression was evident for stimulation intervals greater-than-or-equal-to 5 s. Under these conditions, short tetanic trains (5 pulses at 25 Hz) revealed a substantial facilitation and potentiation of the EPSPs. 8. We suggest that prolonged depression of synaptic potentials in the neonatal rat reflects decreased transmitter output from the activated afferent terminals. The decrease in transmitter release seems best explained by postulating immature properties of the transmitter release machinery in developing synapses, which prevents sustained transmitter release during moderate stimulation rates.