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.

Figure 1. Developmental alterations in the short-term plasticity and reliability of the intracortical synaptic connections between layer 5A pyramidal neurons

Aa, recordings from synaptically coupled layer 5A pyramidal neurons at postnatal day (P) 14 and P29 showing trains of three presynaptic action potentials at 10 Hz (top traces) and six consecutive traces of associated EPSPs (grey middle traces). The bottom traces show the average EPSPs for each connection. In this example, the immature (P14) connection showed strong short-term depression whilst the more mature connection (P29) displayed paired pulse facilitation, an observation made in ∼40% of connections of at this age. Ab, summary graph showing the change the paired pulse behaviour with age. Three age groups (P14–P15, P18–P20, P25–P29) are shown; circles are paired pulse ratios of individual connections, are averages paired pulse ratios of the three age groups. The red line indicates the average paired pulse ratio for immature synaptic connections, the blue line that for more mature connections. Note that whilst almost all connections at P14–P15 are depressing, those at older ages (P25–P29) vary between weakly depressing and facilitating. Ba, recordings from synaptically coupled layer 5A pyramidal neurons at P15 and P28. Seven consecutive postsynaptic responses (grey traces, middle row) to action potentials evoked in the presynaptic neuron (top row) are shown. While the response amplitude is stable for the P15 connection, the amplitude is more variable in the mature connections and occasionally failures can be observed in P28 connections. The bottom row gives the average EPSP for each connection, which was generally smaller for more mature connections. Bb, summary graph showing the developmental alteration of the coefficient of EPSP amplitude variation (CV). Three age groups (P14–P16, P18–P20, P25–P29) are shown; circles are CVs of individual connections, diamond average CVs of the three age groups. The red line indicates the average CV for immature synaptic connections, the blue line that for more mature connections. With maturation, the CV increases, which suggests a reduction in the probability of transmitter release at this synapse. Figure modified from Frick et al. 2007.