Adaptations to glutamate receptor inactivity in developing hippocampal neurons
Description
During the development of neuronal networks, ionotropic glutamate receptor signaling regulates both activity-dependent morphological plasticity and homeostatic synaptic plasticity. Dependent upon the strength of the afferent glutamatergic input, the interplay between these two processes likely determines the activity features of the mature network. However, it has not been shown whether the relative strength of the glutamate signal leads to proportional and relative plasticity-mediated adaptions in developing networks. Here, I show that by blocking activity prior to synaptogenesis, with two proportional levels of a combination of ionotropic glutamate receptor antagonists, and examining after putative synaptic maturation, both groups exhibited significant recovery of some activity-related parameters. These parameters included an increase in the incidence and frequency of Ca2+ transients, an increased amplitude of Ca2+ responses to bath applied glutamate, an increase in intrinsic excitability and the ability to induce non-NMDA receptor-mediated synchronized bursting upon disinhibition. Concomitantly, when removed from their respective concentrations of antagonists, I found proportional regulation of Ca2+ responses to bath applied glutamate and a tending towards a proportional increase in mEPSC frequency. In addition, I found proportional regulation of the AMPA subunit, GluR1 expression, the NMDA receptor subunit, NR1 expression and the expression of the beta-subunit of CaMKII. This work suggests that the activity properties of mature cultured hippocampal networks are function of the relative ionotropic glutamate signal through the period of synaptogenesis