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bioRxiv · 10.1101/405829

Soma-axon coupling configurations that enhance neuronal coincidence detection

Goldwyn, J. H.·Remme, M.·Rinzel, J.
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Abstract

Coincidence detector neurons transmit timing information by responding preferentially to concurrent synaptic inputs. Principal cells of the medial superior olive (MSO) in the mammalian auditory brainstem are superb coincidence detectors. They encode sound source location with high temporal precision, distinguishing submillisecond timing differences among inputs. We investigate computationally how dynamic coupling between the \"input\" region (soma and dendrite) and the spike-generating \"output\" region (axon and axon initial segment) can enhance coincidence detection in MSO neurons. To do this, we formulate a two-compartment neuron model and characterize extensively coincidence detection sensitivity throughout a parameter space of coupling configurations. We focus on the interaction between coupling configuration and two currents that provide dynamic, voltage-gated, negative feedback in subthreshold voltage range: sodium current with rapid inactivation and low-threshold potassium current, IKLT. These currents reduce synaptic summation and can prevent spike generation unless inputs arrive with near simultaneity. We show that strong soma-to-axon coupling promotes the negative feedback effects of sodium inactivation and is, therefore, advantageous for coincidence detection. Furthermore, the \"feedforward\" combination of strong soma-to-axon coupling and weak axon-to-soma coupling enables spikes to be generated efficiently (few sodium channels needed) and with rapid recovery that enhances high-frequency coincidence detection. These observations detail the functional benefit of the strongly feedforward configuration that has been observed in physiological studies of MSO neurons. We find that IKLT further enhances coincidence detection sensitivity, but with effects that depend on coupling configuration. For instance, in weakly-coupled models, IKLT in the spike-generator compartment enhances coincidence detection more effectively than IKLT in the input compartment. By using a minimal model of soma-to-axon coupling, we connect structure, dynamics, and computation. Here, we consider the particular case of MSO coincidence detectors. In principle, our method for creating and exploring a parameter space of two-compartment models can be applied to other neurons.\n\nAuthor summaryBrain cells (neurons) are spatially extended structures. The locations at which neurons receive inputs and generate outputs are often distinct. We formulate and study a minimal mathematical model that describes the dynamical coupling between the input and output regions of a neuron. We construct our model to reflect known properties of neurons in the auditory brainstem that play an important role in our ability to locate sound sources. These neurons are known as \"coincidence detectors\" because they are most likely to respond when they receive simultaneous inputs. We use simulations to explore coincidence detection sensitivity throughout the parameter space of input-output coupling and to identify the coupling configurations that are best for neural coincidence detection. We find that strong forward coupling (from input region to output region), enhances coincidence detection sensitivity in our model and that low-threshold potassium current further improves coincidence detection. Our study is significant in that we detail how cell structure affects neuronal dynamics and, consequently, the ability of neurons to perform as temporally-precise coincidence detectors.

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Goldwyn, J. H., Remme, M., Rinzel, J.. 2018-08-31. Soma-axon coupling configurations that enhance neuronal coincidence detection. https://doi.org/10.1101/405829

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