Biology subjects

Sierksma, M. C.

Publications and source records attributed to Sierksma, M. C..

4 recordsLinked to original sources

bioRxiv2026

Dissection of the contribution of bushy cell delays to sound localization in juvenile and adult Mongolian gerbils

Sound sources along the azimuth generate interaural time differences in arrival (ITDs) at the ears. According to Jeffress hypothesis, ITDs are detected by coincidence-sensitive neurons of the medial superior olive (MSO) for which a differential axonal delay from each ear to the MSO compensates for the ITDs. The origin and development of these delays remain poorly understood. To this end, we made recordings from bushy cells (BCs), which project to both MSOs, in adult and in 2-4-week-old Mongolian gerbils of either sex. First spike latency revealed a frequency-dependent delay likely originating in the cochlea. Latencies were markedly larger for pure tone stimulation than for complex sounds. Combined with our published recordings from the MSO, we observed a developmental decrease in most delays, including the contralateral BC-to-MSO axonal delay. Unexpectedly, the ipsilateral BC-to-MSO axonal delay did not decrease. Anatomical brainstem reconstructions revealed that the inter-MSO distance was stable whereas the cochlear nucleus-to-MSO distance increased during development. Together, this indicated an increase in axonal propagation velocity, particularly for the contralateral projection. The variability in the averaged firing onset between BCs was found to be as large as the variance in bITDs, suggesting that BCs with matching firing onset are selected to converge onto the same MSO neuron. Together, our results indicate that the developmental speedup of ear-to-MSO delays contributes greatly to bringing the bITDs within their ecological range, but that the difference in path length is not overcome, keeping the ITD tuning biased to contralateral sound sources.

neuroscience↗

bioRxiv2021

Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse.

At synapses, the pre- and postsynaptic cell get so close that currents entering the cleft do not flow exclusively along its conductance, gcl. A prominent example is found in the calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB), where the presynaptic action potential can be recorded in the postsynaptic cell in the form of a prespike. Here, we developed a theoretical framework for ephaptic coupling via the synaptic cleft, and we tested its predictions using the MNTB prespike recorded in voltage-clamp. The shape of the prespike is predicted to resemble either the first or the second derivative of the inverted, presynaptic action potential if cleft currents dissipate either mostly capacitively or resistively, respectively. We found that the resistive dissipation scenario provided a better description of the prespike shape. Its size is predicted to scale with the fourth power of the radius of the synapse, explaining why intracellularly recorded prespikes are uncommon in the central nervous system. We show that presynaptic calcium currents also contribute to the prespike shape. This calcium prespike resembled the first derivative of the inverted calcium current, again as predicted by the resistive dissipation scenario. Using this calcium prespike, we obtained an estimate for gcl of ~1 S. We demonstrate that, for a circular synapse geometry, such as in conventional boutons or the immature calyx of Held, gcl is scale-invariant and only defined by extracellular resistivity, which was ~75 {Omega}cm, and by cleft height. During development the calyx of Held develops fenestrations. We show that these fenestrations effectively minimize the cleft potentials generated by the adult action potential, which might otherwise interfere with calcium channel opening. We thus provide a quantitative account of the dissipation of currents by the synaptic cleft, which can be readily extrapolated to conventional, bouton-like synapses. Author SummaryAt chemical synapses two neurons are separated by a cleft, which is very narrow. As a result, the concentration of released neurotransmitter can rapidly peak, which is essential for fast synaptic transmission. At the same time, the currents that flow across the membranes that face the synaptic cleft are also substantial, and a fraction of these currents will enter the other cell. We made an electronic model of the synaptic cleft, which indicated that if the shape and fraction of these currents are known, the electrical resistance of the synaptic cleft can be inferred. We tested several of the predictions of our model by comparing the membrane currents during a presynaptic action potential in a giant terminal, the calyx of Held, with the much smaller prespike evoked by these currents in the postsynaptic cell. We estimate the cleft resistance to be about 1 M{Omega}, which means that the changes in the cleft potential due to the membrane currents can become large enough to have an impact on voltage-dependent calcium channels controlling neurotransmitter release.

neuroscience↗

bioRxiv2020

Properties of the axial current of retinal ganglion cells at spike initiation

The action potential of most vertebrate neurons initiates in the axon initial segment (AIS), and is then transmitted to the soma where it is regenerated by somatodendritic sodium channels. For successful transmission, the AIS must produce a strong axial current, so as to depolarize the soma to the threshold for somatic regeneration. Theoretically, this axial current depends on AIS geometry and Na+ conductance density. We measured the axial current of mouse RGCs using whole-cell recordings with post-hoc AIS labeling. We found that this current is large, implying high Na+ conductance density, and carries a charge that co-varies with capacitance so as to depolarize the soma by ~30 mV. Additionally, we observed that the axial current attenuates strongly with depolarization, consistent with sodium channel inactivation, but temporally broadens so as to preserve the transmitted charge. Thus, the AIS appears to be organized so as to reliably backpropagate the axonal action potential.

neuroscience↗

bioRxiv2020

Structure-function relation of the developing calyx of Held synapse in vivo

In adult rodents, a principal neuron in the medial nucleus of the trapezoid (MNTB) is generally contacted by a single, giant axosomatic terminal called the calyx of Held. How this one-on-one relation is established is still unknown, but anatomical evidence suggests that during development principal neurons are innervated by multiple calyces, which may indicate calyceal competition. However, in vivo electrophysiological recordings from principal neurons indicated that only a single strong synaptic connection forms per cell. To test whether a mismatch exists between synaptic strength and terminal size, we compared the strength of synaptic inputs with the morphology of the synaptic terminals. In vivo whole-cell recordings of the MNTB neurons from newborn Wistar rats of either sex were made while stimulating their afferent axons, allowing us to identify multiple inputs. The strength of the strongest input increased to calyceal levels in a few days across cells, while the strength of the second strongest input was stable. The recorded cells were subsequently immunolabeled for vesicular glutamate transporters (VGluT) to reveal axosomatic terminals with structured-illumination microscopy. Synaptic strength of the strongest input was correlated with the contact area of the largest VGluT cluster at the soma (r = 0.8), and no indication of a mismatch between structure and strength was observed. Together, our data agree with a developmental scheme in which one input strengthens and becomes the calyx of Held, but not with multi-calyceal competition. Key points summaryO_LIDuring development the giant, auditory calyx of Held forms a one-to-one connection with a principal neuron of the medial nucleus of the trapezoid body. C_LIO_LIWhile anatomical studies described that most of the target cells are temporarily contacted by multiple calyces, multi-calyceal innervation was only sporadically observed in in vivo recordings, suggesting a structure-function discrepancy. C_LIO_LIWe correlated synaptic strength of inputs, identified in in vivo recordings, with post hoc labeling of the recorded neuron and synaptic terminals containing vesicular glutamate transporters (VGluT). C_LIO_LIDuring development only one input increased to the level of the calyx of Held synapse, and its strength correlated with the large VGluT cluster contacting the postsynaptic soma. C_LIO_LIAs neither competing strong inputs nor multiple large VGluT clusters on a single cell were observed, our findings did not indicate a structure-function discrepancy. C_LI

neuroscience↗