Developmental changes in short-term synaptic depression in the neonatal mouse spinal cord

We examined age-dependent changes in short-term synaptic depression of monosynaptic excitatory postsynaptic potentials (EPSPs) recorded in lumbar motoneurons in hemisected spinal cords of neonatal Swiss-Webster mice between postnatal day 2 (P2) and 12 (P12). We used four paradigms that sample the input-output dependence on stimulation history in different but complementary ways: 1) paired-pulse depression; 2) steady-state depression during constant frequency trains; 3) modulation during irregular stimulation sequences; and 4) recovery after high-frequency conditioning trains. Paired-pulse synaptic depression declined more than steady-state depression during 10-pulse trains at frequencies from 0.125 to 8 Hz in this age range. Depression during sequences of irregular stimulations that more closely mimic physiological activation also declined with postnatal age. On the other hand, the overall rate of synaptic recovery after a 4-Hz conditioning train exhibited surprisingly little change between P2 and P12. Control experiments indicated that these observations depend primarily, if not exclusively, on changes in presynaptic transmitter release. The data were examined using quantitative models that incorporate factors that have been suggested to exist at more specialized central synapses. The model that best predicted the observations included two presynaptic compartments that are depleted during activation, plus two superimposed processes that enhance transmitter release by different mechanisms. One of the latter produced rapidly-decaying enhancement of transmitter release fraction. The other mechanism indirectly enhanced the rate of renewal of one of the depleted presynaptic compartments. This model successfully predicted the constant frequency and irregular sequence data from all age groups, as well as the recovery curves following short, high-frequency tetani. The results suggest that a reduction in release fraction accounts for much of the decline in synaptic depression during early postnatal development, although changes in both enhancement processes also contribute. The time constants of resource renewal showed surprisingly little change through the first 12 days of postnatal life.