Fully-primed slowly-recovering vesicles mediate presynaptic LTP at neocortical neurons

Weichard, I.; Taschenberger, H.; Gsell, F.; Bornschein, G.; Ritzau-Jost, A.; Schmidt, H.; Kittel, R. J.; Eilers, J.; Neher, E.; Hallermann, S.; Nerlich, J.

doi:10.1101/2023.04.11.535831

bioRxiv · 10.1101/2023.04.11.535831

Fully-primed slowly-recovering vesicles mediate presynaptic LTP at neocortical neurons

Weichard, I.·Taschenberger, H.·Gsell, F.·Bornschein, G.·Ritzau-Jost, A.·Schmidt, H.·Kittel, R. J.·Eilers, J.·Neher, E.·Hallermann, S.·Nerlich, J.

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Abstract

Pre- and postsynaptic forms of long-term potentiation (LTP) are candidate synaptic mechanisms underlying learning and memory. At layer 5 pyramidal neurons LTP increases the initial synaptic strength but also short-term depression during high-frequency transmission. This classical form of presynaptic LTP has been referred to as redistribution of synaptic efficacy. However, the underlying mechanisms remain unclear. We therefore performed whole-cell recordings from layer 5 pyramidal neurons in acute cortical slices of rats and analyzed presynaptic function before and after LTP induction by paired pre- and postsynaptic neuronal activity. LTP was successfully induced in about half of the synaptic connections tested and resulted in increased synaptic depression during high-frequency transmission and a decelerated recovery from depression due to an increased occurrence of a slow recovery component. Analysis with a recently established sequential two-step vesicle priming model indicates an increase in the abundance of fully-primed and slowly-recovering vesicles. A systematic analysis of short-term plasticity and synapse-to-synapse variability of synaptic strength at various types of synapses revealed that stronger synapses generally recover more slowly from synaptic depression. Finally, pharmacological stimulation of the cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG) signaling pathways, which are both known to promote synaptic vesicle priming mimicked electrically-induced LTP and slowed the recovery from depression. Our data thus demonstrate that LTP at layer 5 pyramidal neurons increases synaptic strength primarily by enlarging a subpool of fully-primed slowly-recovering vesicles.

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Weichard, I., Taschenberger, H., Gsell, F., Bornschein, G., Ritzau-Jost, A., Schmidt, H., Kittel, R. J., Eilers, J., Neher, E., Hallermann, S., Nerlich, J.. 2023-04-11. Fully-primed slowly-recovering vesicles mediate presynaptic LTP at neocortical neurons. https://doi.org/10.1101/2023.04.11.535831

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