Astrocyte mediated switch in spike timing dependent plasticity during hippocampal development
Presynaptic spike timing dependent long term depression (t LTD) at hippocampal CA3 CA1 synapses is evident until the 3rd postnatal week in mice, disappearing during the 4th week. At more mature stages, we found that the protocol that induced t LTD induced t LTP. We characterized this form of t LTP and the mechanisms involved in its induction, as well as that driving this switch from t LTD to t LTP. We found that this t LTP is expressed presynaptically at CA3 CA1 synapses, as witnessed by coefficient of variation, number of failures, paired pulse ratio and miniature responses analysis. Additionally, this form of presynaptic t LTP does not require NMDARs but the activation of mGluRs and the entry of Ca2+ into the postsynaptic neuron through L type voltage dependent Ca2+ channels and the release of Ca2+ from intracellular stores. Nitric oxide is also required as a messenger from the postsynaptic neuron. Crucially, the release of adenosine and glutamate by astrocytes is required for t LTP induction and for the switch from t LTD to t LTP. Thus, we have discovered a developmental switch of synaptic transmission from t LTD to t LTP at hippocampal CA3 CA1 synapses in which astrocytes play a central role and revealed a form of presynaptic LTP and the rules for its induction.
Nature communications