Reliability of Synaptic Transmission at the Synapses of Held In Vivo under Acoustic Stimulation

BACKGROUND:The giant synapses of Held play an important role in high-fidelity auditory processing and provide a model system for synaptic transmission at central synapses. Whether transmission of action potentials can fail at these synapses has been investigated in recent studies. At the endbulbs of Held in the anteroventral cochlear nucleus (AVCN) a consistent picture emerged, whereas at the calyx of Held in the medial nucleus of the trapezoid body (MNTB) results on the reliability of transmission remain inconsistent. In vivo this discrepancy could be due to the difficulty in identifying failures of transmission. METHODS/FINDINGS:We introduce a novel method for detecting unreliable transmission in vivo. Based on the temporal relationship between a cells' waveform and other potentials in the recordings, a statistical test is developed that provides a balanced decision between the presence and the absence of failures. Its performance is quantified using simulated voltage recordings and found to exhibit a high level of accuracy. The method was applied to extracellular recordings from the synapses of Held in vivo. At the calyces of Held failures of transmission were found only rarely. By contrast, at the endbulbs of Held in the AVCN failures were found under spontaneous, excited, and suppressed conditions. In accordance with previous studies, failures occurred most abundantly in the suppressed condition, suggesting a role for inhibition. CONCLUSIONS/SIGNIFICANCE:Under the investigated activity conditions/anesthesia, transmission seems to remain largely unimpeded in the MNTB, whereas in the AVCN the occurrence of failures is related to inhibition and could be the basis/result of computational mechanisms for temporal processing. More generally, our approach provides a formal tool for studying the reliability of transmission with high statistical accuracy under typical in vivo recording conditions

Multidimensional Characterization and Differentiation of Neurons in the Anteroventral Cochlear Nucleus

Multiple parallel auditory pathways ascend from the cochlear nucleus. It is generally accepted that the origin of these pathways are distinct groups of neurons differing in their anatomical and physiological properties. In extracellular in vivo recordings these neurons are typically classified on the basis of their peri-stimulus time histogram. In the present study we reconsider the question of classification of neurons in the anteroventral cochlear nucleus (AVCN) by taking a wider range of response properties into account. The study aims at a better understanding of the AVCN's functional organization and its significance as the source of different ascending auditory pathways. The analyses were based on 223 neurons recorded in the AVCN of the Mongolian gerbil. The range of analysed parameters encompassed spontaneous activity, frequency coding, sound level coding, as well as temporal coding. In order to categorize the unit sample without any presumptions as to the relevance of certain response parameters, hierarchical cluster analysis and additional principal component analysis were employed which both allow a classification on the basis of a multitude of parameters simultaneously. Even with the presently considered wider range of parameters, high number of neurons and more advanced analytical methods, no clear boundaries emerged which would separate the neurons based on their physiology. At the current resolution of the analysis, we therefore conclude that the AVCN units more likely constitute a multi-dimensional continuum with different physiological characteristics manifested at different poles. However, more complex stimuli could be useful to uncover physiological differences in future studies

Origin of intrinsic irregular firing in cortical interneurons

Cortical spike trains are highly irregular both during ongoing, spontaneous activity and when driven at high firing rates. There is uncertainty about the source of this irregularity, ranging from intrinsic noise sources in neurons to collective effects in large-scale cortical networks. Cortical interneurons display highly irregular spike times (coefficient of variation of the interspike intervals >1) in response to dc-current injection in vitro. This is in marked contrast to cortical pyramidal cells, which spike highly irregularly in vivo, but regularly in vitro. We show with in vitro recordings and computational models that this is due to the fast activation kinetics of interneuronal K+ currents. This explanation holds over a wide parameter range and with Gaussian white, power-law, and Ornstein-Uhlenbeck noise. The intrinsically irregular spiking of interneurons could contribute to the irregularity of the cortical network

Neuronal responses to omitted tones in the auditory brain: A neuronal correlate for predictive coding

Prediction provides key advantages for survival, and cognitive studies have demonstrated that the brain com- putes multilevel predictions. Evidence for predictions remains elusive at the neuronal level because of the com- plexity of separating neural activity into predictions and stimulus responses. We overcome this challenge by recording from single neurons from cortical and subcortical auditory regions in anesthetized and awake prep- arations, during unexpected stimulus omissions interspersed in a regular sequence of tones. We find a subset of neurons that responds reliably to omitted tones. In awake animals, omission responses are similar to anesthe- tized animals, but larger and more frequent, indicating that the arousal and attentional state levels affect the degree to which predictions are neuronally represented. Omission-sensitive neurons also responded to frequen- cy deviants, with their omission responses getting emphasized in the awake state. Because omission responses occur in the absence of sensory input, they provide solid and empirical evidence for the implementation of a predictive process.This work was supported by project PID2019-104570RB-I00 funded by MCIN/AEI/10.13039/501100011033 (to M.S.M.) and Foundation Ramón Areces grant CIVP20A6616 (to M.S.M. and D.P.-G.), European Union’s Horizon 2020 grant agreement no. 952378—BrainTwin (to M.S.M., D.P.-G., and A.B.L.-R.), Foundation Ramón Areces grant CIVP20A6616 (to M.S.M. and D.P.-G.), NWO-VIDI grant 016.VIDI.189.052 (to B.E., K.P., and A.A.), NWO-ALW-Open grant (ALWOP-346) (to K.P.), iNavigate grant H2020-MS-CA-RISE-2019-873178 (to E.Y.), and NeurotechEU grant EPP-EUR-UNIV-2020-101004080 (to E.Y.)

Zebrafish RTRBM

Code and data accompanying The Recurrent Temporal Restricted Boltzmann Machine Captures Neural Assembly Dynamics in Whole-brain Activity Sebastian Quiroz Monnens, Casper Peters, Kasper Smeets, Luuk Willem Hesselink, Bernhard Englitz bioRxiv 2024.02.02.578570; doi: https://doi.org/10.1101/2024.02.02.578570 Up-to-date code versions can be found at https://github.com/benglitz/Zebrafish_RTRB