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• W4283764663 endingPage "6052" @default.
• W4283764663 startingPage "6038" @default.
• W4283764663 abstract "During development, critical periods of synaptic plasticity facilitate the reordering and refinement of neural connections, allowing the definitive synaptic circuits responsible for correct adult physiology to be established. The L4–L2/3 synapses in the somatosensory cortex (S1) exhibit a presynaptic form of spike timing-dependent long-term depression (t-LTD) that probably fulfills a role in synaptic refinement. This t-LTD persists until the fourth postnatal week in mice, disappearing thereafter. When we investigated the mechanisms underlying this maturation-related loss of t-LTD in either sex mouse slices, we found that it could be completely recovered by antagonizing adenosine type 1 receptors. By contrast, an agonist of A₁R impeded the induction of t-LTD at P13–27. Furthermore, we found that the adenosine that mediated the loss of t-LTD at the end of the fourth week of development is most probably supplied by astrocytes. At more mature stages (P38–60), we found that the protocol used to induce t-LTD provokes t-LTP. We characterized the mechanisms underlying the induction of this form of LTP, and we found it to be expressed presynaptically, as witnessed by paired-pulse and coefficient of variation analysis. In addition, this form of presynaptic t-LTP requires the activation of NMDARs and mGlu1Rs, and the entry of Ca²⁺ into the postsynaptic neuron through L-type voltage-dependent Ca²⁺ channels. Nitric oxide is also required for t-LTP as a messenger in the postsynaptic neuron as are the adenosine and glutamate that are released in association with astrocyte signaling. These results provide direct evidence of the mechanisms that close the window of plasticity associated with t-LTD and that drive the switch in synaptic transmission from t-LTD to t-LTP at L4–L2/3 synapses, in which astrocytes play a central role. <b>SIGNIFICANCE STATEMENT</b> During development, critical periods of plasticity facilitate the reordering and refining of neural connections, allowing correct adult physiology to be established. The L4–L2/3 synapses in the somatosensory cortex exhibit a presynaptic form plasticity (LTD) that probably fulfills a role in synaptic refinement. It is present until the fourth postnatal week in mice, disappearing thereafter. The mechanisms that are responsible for this loss of plasticity are not clear. We describe here these mechanisms and those involved in the switch from LTD to LTP observed as the brain matures. Defining these events responsible for closing (and opening) plasticity windows may be important for brain repair, sensorial recovery, the treatment of neurodevelopmental disorders, and for educational policy." @default.
• W4283764663 created "2022-07-02" @default.
• W4283764663 creator A5012752153 @default.
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• W4283764663 creator A5090999187 @default.
• W4283764663 date "2022-06-29" @default.
• W4283764663 modified "2023-10-02" @default.
• W4283764663 title "Adenosine and Astrocytes Determine the Developmental Dynamics of Spike Timing-Dependent Plasticity in the Somatosensory Cortex" @default.
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