Abstract
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.
Highlights
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
Characterizing this form of t-Long-term potentiation (LTP), the result of a switch from presynaptic t-LTD, coefficient of variation, number of failures, paired-pulse ratio (PPR) and miniature responses analyses demonstrate its presynaptic nature. This form of presynaptic timing-dependent LTP (t-LTP) does not require NMDARs but requires mGluR5 activation. We find that this presynaptic t-LTP requires the flux of calcium through postsynaptic L-type calcium channels, as well as calcium release from intracellular stores
No t-LTD was observed at P22–30, yet when the same protocol was applied at P35–42 a robust t-LTP was surprisingly observed (141 ± 5%, n = 13 vs 100 ± 4%, n = 13 in the unpaired pathway, Fig. 1b–d)
Summary
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. 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, pairedpulse ratio and miniature responses analysis. 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. Spike timing-dependent plasticity (STDP) is a Hebbian form of long-term synaptic plasticity detected in all species examined to date, from insects to humans This process is a strong candidate to underlie circuit remodeling during development, as well as that in subsequent learning and memory[6]. Timing-dependent LTP (t-LTP) occurs when a presynaptic spike is followed by a postsynaptic spike, whereas timing-dependent LTD (t-LTD) is induced when this order is inverted, exceptions exist[6,7]
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