Critical Roles of Voltage-Dependent Sodium Channels in the Process of Synaptogenesis During the Postnatal Cortical Development of Rats

Abstract

The developmental changes of the sodium channel and construction of synapse connection were studied in cerebral cortical pyramidal neurons of rats at different age groups. We used whole-cell patch-clamp recordings to characterize electrophysiological properties of cortical neurons at different age stages, including the sodium currents, APs evoked by depolarizing current and short-term plasticity of the eEPSCs. The result shows that the sodium currents undergo a hyperpolarizing shift in activation process and acceleration of activation and inactivation with age. The maximal sodium current also increased with maturation, and the evident difference appeared from P7-P11 (with the day of birth as P0) to P12-P15 group. The tendency of the sodium current density changes which exhibited the same properties as that of sodium current, showed the significant increases from P19-P21 to P >or= 22 group. The APs' parameters exhibited the age-dependent changes except the threshold, including the increase of the peak amplitude from P <or= 6 to P16-P18 groups, and the curtailment of duration and the time-to-peak with age. The amplitude of 1st eEPSC increased with maturation, and STP displays depression at all observed groups. In addition, although STP also exhibited depression in response to last three stimulations in P >or= 22 group, the 2nd response showed the tendency of facilitation compared with the younger age groups. Our results indicated that the cerebral cortical pyramidal neurons of rats are undergoing marked changes in the characteristics of their sodium channels with maturation, which play a critical role in synaptogenesis and construction of the neuronal network.

GABAergic Signaling Increases Through the Postnatal Development to Provide the Potent Inhibitory Capability for the Maturing Demands of the Prefrontal Cortex

“…(Kim and Park 2009). Consistent to our previous study on pyramidal cells (Wang et al 2009), many LTS interneurons younger than P7 did not give all five responses, even the first response was not induced either. This phenomenon indicated that, in early age stage (P \ 7), the developmental changes of both the pyramidal cells and interneurons embodied in the intrinsic parameters of individual neuron primarily such as sodium channel increases, size augment and enhancement of excitability.…”

“…Previous studies presented that pyramidal cells showed significant intrinsic changes in almost postnatal 2-3 weeks in the somatosensory cortex (Wang et al 2009) and in PFC (Zhang 2004), while LTS interneurons in the PFC exhibited a developmental delay in the process of maturation, which were in accordance with the other reports about the maturation of the GABAergic signaling systems (Douglas and Martin 2009). During the early postnatal period, maybe the development of LTS interneurons directly depends on the growth of excitatory pyramidal cells.…”

“…And the STP of eEPSCs was quantified by normalizing the amplitude of all five responses to that of the first one. Incompatible to the report by Wang et al (2009) on pyramidal cells, it was found that, in response to the five stimulations, STP of LTS interneurons displayed synaptic facilitation (increased the magnitude of the summed current) in all researched age groups, and this facilitation enhanced from P7-P11 (n = 6) to P16-P19 (n = 25) group, weakened from P20-P23 (n = 33) to P [ 27 Fig. 4 The short-term plasticity (STP) of eEPSCs in cortex at different developmental stages.…”

“…As our results shown that the amplitudes of 1st and 5th eEPSC both increased with age, it was indicated that these age-dependent changes were not only attributed to the functional maturation of individual synapse such as the increase of the number of receptors, release probability, and/or quantum size of presynaptic vesicles, but also attributed to the reinforcement of complexity of the whole synaptic connections (Takai et al 2003;Ye et al 2005;Wang et al 2009). Developmental changes of decay-rate of 1st and 5th eEPSC may be due to the fact that synaptic responses at early ages (from P7-P11 to P16-P19 group) have a large NMDA component with slow kinetics, whereas a fast AMPA component becomes dominant at older age stages (from P20-P23 to P [ 27 group) (Crair and Malenka 1995;Ramoa and McCormick 1994).…”

“…It was shown that the amplitude of sIPSC decreased and frequency remained unaltered leading to developmental down-regulation of GABAergic drive during maturation in culture mouse neocortical network. Second, compared with our previous study on pyramidal cells (Wang et al 2009), the amplitude of eEPSC in pyramidal cells and LTS interneurons both increased with age, which were consistent with other reports that both hyperpolarizing GABAergic inhibition and glutamatergic excitation are relatively weak during early development, and both increased as development progresses (Dunning et al 1999;Liu 2004). But it should be pointed out that the significant enhancement of eEPSC amplitude in pyramidal cells was appeared from P7-P11 to P12-P15 group, while that of eEPSC, sEPSC, and sIPSC in LTS interneurons were shown nearly 3-4 weeks after birth until the last test period in our research (from P20-P23 to P [ 27).…”