No abstract

Spike-timing-dependent plasticity (STDP) is a candidate mechanism for information storage in the brain, but the whole-cell recordings required for the experimental induction of STDP are typically limited to 1 h. This mismatch of time scales is a long-standing weakness in synaptic theories of memory. Here we use spectrally separated optogenetic stimulation to fire precisely timed action potentials (spikes) in CA3 and CA1 pyramidal cells. Twenty minutes after optogenetic induction of STDP (oSTDP), we observed timing-dependent depression (tLTD) and timing-dependent potentiation (tLTP), depending on the sequence of spiking. As oSTDP does not require electrodes, we could also assess the strength of these paired connections three days later. At this late time point, late tLTP was observed for both causal (CA3 before CA1) and anticausal (CA1 before CA3) timing, but not for asynchronous activity patterns (Δt = 50 ms). Blocking activity after induction of oSTDP prevented stable potentiation. Our results confirm that neurons wire together if they fire together, but suggest that synaptic depression after anticausal activation (tLTD) is a transient phenomenon.

Summary Shrinkage and loss of dendritic spines are vital components of the neuronal plasticity that supports learning. To investigate the mechanisms of spine shrinkage and loss, Oh and colleagues established a two-photon glutamate uncaging protocol that reliably induces input-specific spine shrinkage on dendrites of rodent hippocampal CA1 pyramidal neurons. Here, we provide a detailed description of that protocol and also an optimized version that can be used to induce input- and synapse-specific shrinkage of dendritic spines at physiological Ca 2+ levels. For complete details on the use and execution of this protocol, please refer to Oh et al. (2013) , Stein et al. (2015) , Stein et al. (2020) , and Stein et al. (2021) .

Spike-timing-dependent plasticity (STDP) is a candidate mechanism for information storage in the brain. However, it has been practically impossible to assess the long-term consequences of STDP as recordings from postsynaptic neurons last at most one hour. We assessed both the short-term (20 minutes) and long-term (3 days) effects of optically-induced STDP (oSTDP) using two colors of light to independently activate CA3 and CA1 neurons expressing the opsins ChrimsonR and CheRiff. During patch-clamp recordings short-term effects followed classic STDP rules, synapses potentiated when postsynaptic spikes followed presynaptic spikes (tLTP, causal pairing) and depressed when postsynaptic spikes were first (tLTD, anti-causal pairing). Surprisingly, three days after inducing oSTDP without patching the neurons, tLTP was evident regardless of pairing sequence. Potentiation depended on NMDA receptors and spontaneous activity was necessary in the two days following oSTDP. Our data suggest that tLTD at Schaffer collateral synapses is a transitory phenomenon or a recording artifact.