Developmental alterations in the functional properties of excitatory neocortical synapses

Abstract

In the neocortex, most excitatory, glutamatergic synapses are established during the first 4-5 weeks after birth. During this period profound changes in the properties of synaptic transmission occur. Excitatory postsynaptic potentials (EPSPs) at immature synaptic connections are profoundly and progressively reduced in response to moderate to high frequency (5-100 Hz) stimulation. With maturation, this frequency-dependent depression becomes progressively weaker and may eventually transform into a weak to moderate EPSP facilitation. In parallel to changes in the short-term plasticity, a reduction in the synaptic reliability occurs at most glutamatergic neocortical synapses: immature synapses show a high probability of neurotransmitter release as indicated by their low failure rate and small EPSP amplitude variation. This high reliability is reduced in mature synapses, which show considerably higher failure rates and more variable EPSP amplitudes. During early neocortical development synaptic vesicle pools are not yet fully differentiated and their replenishment may be slow, thus resulting in EPSP amplitude depression. The decrease in the probability of neurotransmitter release may be the result of an altered Ca 2+ control in the presynaptic terminal with a reduced Ca 2+ influx and/or a higher Ca 2+ buffering capacity. This may lead to a lower synaptic reliability and a weaker short-term synaptic depression with maturation.

Postnatal Development of Intrinsic and Synaptic Properties Transforms Signaling in the Layer 5 Excitatory Neural Network of the Visual Cortex

“…At this developmental stage (P11-P15), L5 neurons also exhibit a long membrane time constant. In concert with the large amplitude and slow kinetics of uEPSPs, this will act to maximize the temporal summation of synaptic potentials and so promote activity-dependent stabilization of salient connections during cortical map refinement, consistent with findings from the somatosensory system (Feldmeyer and Radnikow, 2009). Interestingly, we observed that this transition in the properties of unitary excitatory synaptic transmission was accompanied by a marked and rapid development of the properties of presynaptic action potentials, which approached mature values by P15.…”

“…The use-dependent properties of synaptic transmission are particularly important for shaping information transfer at cortical connections in an activity-and frequency-dependent manner (for review, see Feldmeyer and Radnikow, 2009). We thus explored how connections in the two age groups process more complex, time-varying patterns of presynaptic AP firing.…”

Developmental Changes in Short-Term Plasticity at the Rat Calyx of Held Synapse

“…Since quantal analysis suggested release probability to be low in the young-adult calyx of Held (Lorteije et al, 2009), it seems likely that the developmental reduction of release probability made a large contribution to the decreased impact of short-term depression. A developmental reduction of release probability has also been observed at other synapses, for example in cortex (for review, see Feldmeyer and Radnikow, 2009). …”

Emergence of Adaptive Computation by Single Neurons in the Developing Cortex

“…The developmental period we investigated is also characterized by significant synaptic maturation (Garaschuk et al, 2000;McCabe et al, 2007;Feldmeyer and Radnikow, 2009); determining how changing synaptic inputs interact with the developing gain-scaling properties of single cortical neurons is an open question. It is possible that intrinsic somatic properties can serve to alleviate or normalize out the effects of changes in synaptic filtering that help to shape the statistics of the input to the soma.…”