Astrocyte-mediated switch in spike timing-dependent plasticity during hippocampal development

Abstract

Presynaptic spike timing-dependent long-term depression (t-LTD) at hippocampal CA3-CA1 synapses is evident until the 3 rd postnatal week in mice, disappearing during the 4 th 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, pairedpulse 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 Ca 2+ into the postsynaptic neuron through L-type voltage-dependent Ca 2+ channels and the release of Ca 2+ 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.

Input-selective adenosine A1 receptor-mediated synaptic depression of excitatory transmission in dorsal striatum

“…Evidence for tonic inhibition by A1Rs has been found in other brain regions, however, such as the hippocampus. Application of the same A1R antagonist in the current study, CPT, produced increases in evoked EPSPs in the CA1 region of the of the hippocampus 42 , 43 . Interestingly, this effect became stronger over the course of postnatal development.…”

Astrocyte-mediated spike-timing-dependent long-term depression modulates synaptic properties in the developing cortex

“…The exact signaling between astrocytic CB 1 Rs and presynaptic NMDARs cooperatively leading to synaptic depression is, however, not fully understood. Moreover, the presynaptic NMDAR-dependent LTD (in the vertical pathway) seems to be developmentally regulated and disappears by 3–4 weeks of age in the mouse barrel cortex [ 10 ] and visual cortex [ 105 ] as well as in the mouse hippocampus [ 41 ]. Regardless of the few missing components and debates on the exocytosis of astrocytic glutamate and the presynaptic NMDARs [ 14 , 17 , 29 , 106 – 108 ], we conclude that there is a growing body of evidence suggesting the involvement of astrocytes in t-LTD during postnatal development.…”

“…Several lines of evidence suggest that, through this close association with neurons, astrocytes alter synaptic functions. Astrocytes have been shown to modulate synaptic transmission [33,34], long-term potentiation [34][35][36][37][38][39][40], and long-term depression [15] in several brain areas, as well as provide a developmental switch of synaptic transmission from LTD to LTP in hippocampus [41]. More and more details about astrocytic cellular and subcellular mechanisms have recently been presented [40,[42][43][44][45][46][47][48][49].…”

The role of astrocyte‐mediated plasticity in neural circuit development and function

“…Interestingly, the authors also found that while direct neuronal activation impaired memory formation, delayed activation through astrocytes strongly enhanced memory allocation [ 190 ], suggesting that indirect signaling through astrocytes may be necessary to gate LTP. Indeed, a recent report suggests that gliotransmission by astrocytes recruits metabotropic glutamate receptors to the presynaptic terminal during spike timing-dependent plasticity, a process that shifts developing hippocampal synapses from long term depression (LTD) to LTP [ 191 , 192 ] (Fig. 3 ).…”