Biology subjects

Kuokkanen, P. T.

Publications and source records attributed to Kuokkanen, P. T..

4 recordsLinked to original sources

bioRxiv2025

Inhibitory inputs to avian ITD circuits

In birds, detection of sound source azimuth begins in the nucleus laminaris (NL), which computes interaural time differences (ITDs). Inhibition has been proposed to protect NL neurons from losing ITD sensitivity with increasing sound level, although the nature of this inhibition is incompletely understood. Anatomical studies show GABAergic synapses throughout NL and the first order nuclei, while in vitro studies in chicken NL showed that depolarizing, GABAergic inhibitory postsynaptic potentials (IPSPs) shorten membrane time constants, perhaps to allow the membrane potential to follow rapid synaptic currents accurately over a range of sound levels. Given the importance of inhibition in regulating auditory brainstem activity, we examined the nature of the inhibitory input to NL in vivo. The Superior Olivary Nucleus (SON) is the major source of descending GABAergic inhibition to the ipsilateral nucleus magnocellularis (NM), nucleus angularis (NA) and NL, and receives excitatory input from NA and NL. We used viral tracers to reveal projections from SON to NL, and characterized response types within SON. In NL, we isolated inhibitory synaptic contributions from extracellular field potentials through the iontophoretic application of blockers of GABA (gabazine) or glycine (strychnine). These blockers increase the onset and offset responses evoked by tonal stimuli, but did not shift best ITD. The co-application of gabazine and strychnine revealed supra-linear summation of GABA and glycine. Profiles of synaptic activation revealed more prominent inhibition following stimulus offset, suggesting inputs to NL originate from both the sustained and offset response types of the SON. These heterogeneous responses may represent separate SON neuronal populations.

neuroscience↗

bioRxiv2024

Single neuron contributions to the auditory brainstem EEG

The auditory brainstem response (ABR) is an acoustically evoked EEG potential that is an important diagnostic tool for hearing loss, especially in newborns. The ABR originates from the response sequence of auditory nerve and brainstem nuclei, and a click-evoked ABR typically shows three positive peaks ( waves) within the first six milliseconds. However, an assignment of the waves of the ABR to specific sources is difficult, and a quantification of contributions to the ABR waves is not available. Here, we exploit the large size and physical separation of the barn owl first-order cochlear nucleus magnocellularis (NM) to estimate single-cell contributions to the ABR. We simultaneously recorded NM neurons spikes and the EEG in owls of both sexes, and found that {gtrsim} 5, 000 spontaneous single-cell spikes are necessary to isolate a significant spike-triggered average response at the EEG electrode. An average single-neuron contribution to the ABR was predicted by convolving the spike-triggered average with the cells peri-stimulus time histogram. Amplitudes of predicted contributions of single NM cells typically reached 32.9 {+/-} 1.1 nV (mean {+/-} SE, range: 2.5 - 162.7 nV), or 0.07 {+/-} 0.02% (median {+/-} SE; range from 0.01% to 1%) of the ABR amplitude. The time of the predicted peak coincided best with the peak of the ABR wave II, independent of the click sound level. Our results suggest that individual neurons contributions to an EEG can vary widely, and that wave II of the ABR is shaped by NM units. Significance statementThe auditory brainstem response (ABR) is a scalp potential used for the diagnosis of hearing loss, both clinically and in research. We investigated the contribution of single action potentials from auditory brainstem neurons to the ABR and provide direct evidence that action potentials recorded in a first order auditory nucleus, and their EEG contribution, coincide with wave II of the ABR. The study also shows that the contribution of single cells varies strongly across the population.

neuroscience↗

bioRxiv2023

Experience-Dependent Plasticity in Nucleus Laminaris of the Barn Owl

Barn owls experience increasing interaural time differences (ITDs) during development, because their head width more than doubles in the month after hatching. We therefore hypothesized that their ITD detection circuit might be modified by experience. To test this, we raised owls with unilateral ear inserts that delayed and attenuated the acoustic signal, then measured the ITD representation in the brainstem nucleus laminaris (NL) when they were adult. The ITD circuit is composed of delay line inputs to coincidence detectors, and we predicted that plastic changes would lead to shorter delays in the axons from the manipulated ear, and complementary shifts in ITD representation on the two sides. In owls that received ear inserts starting around P14, the maps of ITD shifted in the predicted direction, but only on the ipsilateral side, and only in those tonotopic regions that had not experienced auditory stimulation prior to insertion. The contralateral map did not change. Experience-dependent plasticity of the ITD circuit occurs in NL, and our data suggest that ipsilateral and contralateral delays are independently regulated. Thus, altered auditory input during development leads to long-lasting changes in the representation of ITD. Significance StatementThe early life of barn owls is marked by increasing sensitivity to sound, and by increasing ITDs. Their prolonged post-hatch development allowed us to examine the role of altered auditory experience on the development of ITD detection circuits. We raised owls with a unilateral ear insert and found that their maps of ITD were altered by experience, but only in those tonotopic regions that had not experienced auditory stimulation prior to insertion. Thus experience-induced plasticity allows the sound localization circuits to be customized to individual characteristics, such as the size of the head, and potentially to compensate for natural conductive hearing losses.

neuroscience↗

bioRxiv2017

Dipolar extracellular potentials generated by axonal projections

Extracellular field potentials (EFPs) are an important source of information in neuroscience, but their physiological basis is in many cases still a matter of debate. Axonal sources are typically discounted in modeling and data analysis because their contributions are assumed to be negligible. Here, we show experimentally and theoretically that contributions of axons to EFPs can be significant. Modeling action potentials propagating along axons, we showed that EFPs were prominent in the presence of a terminal zone where axons branch and terminate in close succession, as found in many brain regions. Our models predicted a dipolar far field and a polarity reversal at the center of the terminal zone. We confirmed these predictions using EFPs from the barn owl auditory brainstem where we recorded in nucleus laminaris using a multielectrode array. These results demonstrate that axonal terminal zones produce EFPs with considerable amplitude and spatial reach.

neuroscience↗