Soma-axon coupling configurations that enhance neuronal coincidence detection

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, I KLT . 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 I KLT further enhances coincidence detection sensitivity, but with effects that depend on coupling configuration. For instance, in weakly-coupled models, I KLT in the spike-generator compartment enhances coincidence detection more effectively than I KLT 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. PLOS1/30 Author 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 neu...

Optical measurement of physiological sodium currents in the axon initial segment

“…Notably, the remarkable SNR allowed detection, in a proportion of cells, of a subthreshold component of the Na + influx occurring during the somatic current injection but before the onset of the AP. A subthreshold Na + current boosts the depolarization in the AIS to reach the firing threshold and it is therefore expected to contribute to the transduction of postsynapic excitatory inputs from the dendrites into the firing output of the neuron (Goldwyn et al 2019). The principal (suprathreshold) current starting at the onset of the AP was visually characterized by two phases: a first phase with a steep fluorescence increase and a second phase with a longer lasting and weaker fluorescence increase due to a slow Na + current.…”

Optical measurement of physiological sodium currents in the axon initial segment

“…Notably, the remarkable SNR allowed detecting, in a proportion of cells, a subthreshold component of the Na + influx occurring during the somatic current injection but before the onset of the AP. A subthreshold Na + current amplifies the transmission of depolarisation from the soma to the axon and it is therefore expected to contribute to the transduction of postsynapic excitatory inputs from the dendrites into the firing output of the neuron (Goldwyn et al 2019). The principal (suprathreshold) current starting at the onset of the AP was visually characterized by two phases: a first phase with a steep fluorescence increase and a second phase with a longer lasting and weaker fluorescence increase due to a slow Na + current.…”

Different dynamical behaviors induced by slow excitatory feedback for type II and III excitabilities

“…Compared with type I and II excitability, there are far fewer investigations of type III excitability [8][9][10]26,27 . Neurons with type III excitability only fire a spike or a few spikes at the onset of step depolarization current stimulation, which is also known as phasic firing 3,5,10 .…”

“…Type III excitability has been observed in neurons such as the spinal cord neuron 6 , dorsal root ganglion neuron 28 , and auditory brain stem neuron [29][30][31] . Neurons with type III excitability exhibit extraordinary temporal precision for phase locking 32 and enhanced coincidence detection 2,9,27 . These properties are related to some physiological 29,31,33 and pathological functions 28,34 .…”