Minimal Number of Required Inputs for Temporally Precise Action Potential Generation in Auditory Brainstem Nuclei

Abstract

The auditory system relies on temporal precise information transfer, requiring an interplay of synchronously activated inputs and rapid postsynaptic integration. During late postnatal development synaptic, biophysical, and morphological features change to enable mature auditory neurons to perform their appropriate function. How the number of minimal required input fibers and the relevant EPSC time course integrated for action potential generation changes during late postnatal development is unclear. To answer these questions, we used in vitro electrophysiology in auditory brainstem structures from pre-hearing onset and mature Mongolian gerbils of either sex. Synaptic and biophysical parameters changed distinctively during development in the medial nucleus of the trapezoid body (MNTB), the medial superior olive (MSO), and the ventral and dorsal nucleus of the lateral lemniscus (VNLL and DNLL). Despite a reduction in input resistance in most cell types, all required fewer inputs in the mature stage to drive action potentials. Moreover, the EPSC decay time constant is a good predictor of the EPSC time used for action potential generation in all nuclei but the VNLL. Only in MSO neurons, the full EPSC time course is integrated by the neuron's resistive element, while otherwise, the relevant EPSC time matches only 5-10% of the membrane time constant, indicating membrane charging as a dominant role for output generation. We conclude, that distinct developmental programs lead to a general increase in temporal precision and integration accuracy matched to the information relaying properties of the investigated nuclei.

Synaptic Mechanisms Underlying Temporally Precise Information Processing in the VNLL, an Auditory Brainstem Nucleus

“…1B, inset). Non-NMDAR-mediated currents reversed at 0 mV and showed strong inward rectification, in agreement with earlier results (Kladisios et al, 2020). This suggests that mainly GluR2 lacking AMPARs known from other auditory brainstem nuclei (Geiger et al, 1995;Lujan et al, 2019;Franzen et al, 2020) are underlying the adaptation of rapid synaptic transmission.…”

“…Previous studies in auditory brainstem neurons have shown that a stimulus waveform influences action potential current thresholds (Cathala et al, 2003;Couchman et al, 2010;Ammer et al, 2012;Lehnert et al, 2014;Franzen et al, 2015;Cao and Oertel, 2017;Kladisios et al, 2020;Bondy et al, 2021). Since VNLL EPSCs exhibited biexponential decay that persisted after NMDAR block (Fig.…”

“…Their modulation transfer functions are tuned for onset responses to envelope sounds in a frequency range ,250 Hz (Zhang and Kelly, 2006a;Recio-Spinoso and Joris, 2014). Biophysically, ventral VNLL neurons are characterized by an onset action potential (Wu, 1999;Caspari et al, 2015;Franzen et al, 2015;Baumann and Koch, 2017;Kladisios et al, 2020), and membrane dynamics that amplify output frequencies ;20 Hz (Fischer et al, 2018). The endbulb inputs are large, fast, and depress during ongoing activity (Wu, 1999;Caspari et al, 2015;Baumann and Koch, 2017;Kladisios et al, 2020).…”

Periodicity Pitch Perception Part III: Sensibility and Pachinko Volatility

“…Subsequently, STDP requires postactivation, which occurs through the generation of a somatic sodium (Na + ) spike that propagates back into the dendrites (Winters and Golding, 2018 ). The briefly previously presensitized synapse is potentiated by the passing backpropagating spike, as these concurrent pre/post stimuli trigger the influx of calcium into the spike head of the synapse (Franzen et al, 2020 ; Kladisios et al, 2020 ). If it is an inhibitory synapse, it will be suppressed.…”

“…In the simplest case, a single distant synaptic input is attenuated and low-pass filtered before it reaches the soma. A single EPSP remains below threshold, and most of the collective synaptic potentials are too weak on their own to trigger a somatic action potential, but some constellations have converging EPSPs that sum at the soma and trigger an AP (Kladisios et al, 2020 ). The dendritic calculation evaluates the threshold crossing condition as a function of the actual sum of EPSPs arriving simultaneously at the soma.…”