Distinct Neuronal Coding Schemes in Memory Revealed by Selective Erasure of Fast Synchronous Synaptic Transmission

Neurons encode information by firing spikes in isolation or bursts and propagate information by spike-triggered neurotransmitter release that initiates synaptic transmission. Isolated spikes trigger neurotransmitter release unreliably but with high temporal precision. In contrast, bursts of spikes trigger neurotransmission reliably (i.e., boost transmission fidelity), but the resulting synaptic responses are temporally imprecise. However, the relative physiological importance of different spike-firing modes remains unclear. Here, we show that knockdown of synaptotagmin-1, the major Ca2+ sensor for neurotransmitter release, abrogated neurotransmission evoked by isolated spikes but only delayed, without abolishing, neurotransmission evoked by bursts of spikes. Nevertheless, knockdown of synaptotagmin-1 in the hippocampal CA1 region did not impede acquisition of recent contextual fear memories, although it did impair the precision of such memories. In contrast, knockdown of synaptotagmin-1 in the prefrontal cortex impaired all remote fear memories. These results indicate that different brain circuits and types of memory employ distinct spike-coding schemes to encode and transmit information. º Burst-evoked synaptic transmission suffices to entrain hippocampus-dependent memory º Precisely timed spikes are indispensible for prefrontal cortex-dependent memory º Prefrontal cortex and hippocampus determine the precision of contextual memories º AAV DJ allows efficient brain region-specific manipulation of gene expression Xu et al. selectively erase fast, synchronous synaptic transmission in vivo, thereby blocking information transfer of isolated spikes, but not of bursts of spikes. This approach reveals distinct coding schemes in memory circuits, with spike bursts sufficient for hippocampal encoding of memories.