Coincidence Detection within the Excitable Rat Olfactory Bulb Granule Cell Spines

In the mammalian olfactory bulb, the inhibitory axonless granule cells (GCs) feature reciprocal synapses that interconnect them with the principal neurons of the bulb, mitral, and tufted cells. These synapses are located within large excitable spines that can generate local action potentials (APs) upon synaptic input ("spine spike"). Moreover, GCs can fire global APs that propagate throughout the dendrite. Strikingly, local postsynaptic Ca²⁺ entry summates mostly linearly with Ca²⁺ entry due to coincident global APs generated by glomerular stimulation, although some underlying conductances should be inactivated. We investigated this phenomenon by constructing a compartmental GC model to simulate the pairing of local and global signals as a function of their temporal separation t. These simulations yield strongly sublinear summation of spine Ca²⁺ entry for the case of perfect coincidence t = 0 ms. Summation efficiency (SE) sharply rises for both positive and negative t. The SE reduction for coincident signals depends on the presence of voltage-gated Na⁺ channels in the spine head, while NMDARs are not essential. We experimentally validated the simulated SE in slices of juvenile rat brain (both sexes) by pairing two-photon uncaging of glutamate at spines and APs evoked by somatic current injection at various intervals t while imaging spine Ca²⁺ signals. Finally, the latencies of synaptically evoked global APs and EPSPs were found to correspond to t 10 ms, explaining the observed approximately linear summation of synaptic local and global signals. Our results provide additional evidence for the existence of the GC spine spike.

SIGNIFICANCE STATEMENT Here we investigate the interaction of local synaptic inputs and global activation of a neuron by a backpropagating action potential within a dendritic spine with respect to local Ca²⁺ signaling. Our system of interest, the reciprocal spine of the olfactory bulb granule cell, is known to feature a special processing mode, namely, a synaptically triggered action potential that is restricted to the spine head. Therefore, coincidence detection of local and global signals follows different rules than in more conventional synapses. We unravel these rules using both simulations and experiments and find that signals coincident within ±7 ms around 0 ms result in sublinear summation of Ca²⁺ entry because of synaptic activation of voltage-gated Na⁺ channels within the spine.

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