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

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Developmental Biology

Background:

• Presynaptic spike timing-dependent long-term depression (t-LTD) is observed at hippocampal CA3-CA1 synapses in young mice.
• This t-LTD disappears by the 4th postnatal week, with a switch to a different form of synaptic plasticity.

Purpose of the Study:

• To characterize the newly identified presynaptic long-term potentiation (t-LTP) at mature CA3-CA1 synapses.
• To elucidate the molecular and cellular mechanisms underlying this t-LTP and the developmental switch from t-LTD to t-LTP.

Main Methods:

• Analysis of synaptic transmission parameters (coefficient of variation, paired-pulse ratio, miniature responses).
• Investigation of molecular pathways including NMDARs, mGluRs, Ca2+ channels, intracellular Ca2+ stores, and nitric oxide.
• Assessment of astrocyte involvement through the release of adenosine and glutamate.

Main Results:

• A novel form of presynaptic t-LTP is induced by protocols previously causing t-LTD in mature mice.
• t-LTP induction requires mGluRs, postsynaptic Ca2+ influx via L-type channels, intracellular Ca2+ release, and nitric oxide.
• Astrocytic release of adenosine and glutamate is essential for t-LTP induction and the developmental switch.

Conclusions:

• A developmental switch from t-LTD to t-LTP occurs at hippocampal CA3-CA1 synapses.
• Astrocytes play a critical role in mediating this switch and inducing presynaptic t-LTP.
• This study reveals a novel form of presynaptic LTP and its induction rules.