How synaptic strength, short-term plasticity, and input synchrony contribute to neuronal spike output

Abstract

Neurons integrate from thousands of synapses whose strengths span an order of magnitude. Intriguingly, in mouse neocortex, the few strong synapses are formed between similarly tuned cells, suggesting they determine neuronal spiking output. This raises the question of how other computational primitives, including background activity from the many weak synapses, short-term plasticity, and temporal factors contribute to spiking. We combined extracellular stimulation and whole-cell recordings in mouse barrel cortex to map excitatory postsynaptic potential (EPSP) amplitudes and paired-pulse ratios of excitatory synaptic connections converging onto individual layer 2/3 (L2/3) neurons. While net short-term plasticity was weak, connections with EPSPs > 2 mV were exclusively depressing. There was no evidence for clustering of synaptic properties on individual neurons. Instead, EPSPs and paired-pulse ratios of connections converging onto the same cells spanned the full range observed across L2/3, which critically constrains theoretical models of cortical filtering. To investigate how different computational primitives of synaptic information processing interact to shape spiking, we developed a computational model of a pyramidal neuron in the rodent L2/3 circuitry, which was constrained by our own experiments and published in vivo data. We found that the ability of strong inputs to evoke spiking depended on their high temporal synchrony and high firing rates observed in vivo and on synaptic background activity - and not primarily on synaptic strength, which further amplified information transfer. Our results provide a framework of how cortical neurons exploit complex synergies between temporal coding, synaptic properties, and noise to transform synaptic inputs into output firing.