Biology subjects

Baayen, J. C.

Publications and source records attributed to Baayen, J. C..

8 recordsLinked to original sources

bioRxiv2022

Human voltage-gated Na+ and K+ channel properties underlie sustained fast AP signaling

Human cortical pyramidal neurons are large, have extensive dendritic trees, and yet have surprisingly fast input-output properties: rapid subthreshold synaptic membrane potential changes are reliably encoded in timing of action potentials (APs). Here, we tested whether biophysical properties of voltage-gated sodium (Na+) and potassium (K+) currents in human pyramidal neurons can explain their fast input-output properties. Human Na+ and K+ currents exhibited more depolarized voltage-dependence, slower inactivation and faster recovery from inactivation compared with their mouse counterparts. Computational modeling showed that despite lower Na+ channel densities in human neurons, the biophysical properties of Na+ channels resulted in higher channel availability and contributed to fast AP kinetics stability. Finally, human Na+ channel properties also resulted in a larger dynamic range for encoding of subthreshold membrane potential changes. Thus, biophysical adaptations of voltage-gated Na+ and K+ channels enable fast input-output properties of large human pyramidal neurons. One-Sentence SummaryBiophysical properties of Na+ and K+ ion channels enable human neurons to reliably encode fast inputs into output.

neuroscience↗

bioRxiv2021

Intracortical human recordings reveal intensity coding for the pain of others in the insula

Based on neuroimaging data, the insula is considered important for people to empathize with the pain of others, whether that pain is perceived through facial expressions or the sight of limbs in painful situations. Here we present the first report of intracranial electroencephalographic (iEEG) recordings from the insulae collected while 7 presurgical epilepsy patients rated the intensity of a womans painful experiences viewed in movies. In two separate conditions, pain was deduced from seeing facial expressions or a hand being slapped by a belt. We found that broadband activity in the 20-190 Hz range correlated with the trial-by-trial perceived intensity in the insula for both types of stimuli. Using microwires at the tip of a selection of the electrodes, we additionally isolated 8 insular neurons with spiking that correlated with perceived intensity. Within the insula, we found a patchwork of locations with differing selectivities within our stimulus set, some representing intensity only for facial expressions, others only for the hand being hit, and others for both. That we found some locations with intensity coding only for faces, and others only for hand across simultaneously recorded locations suggests that insular activity while witnessing the pain of others cannot be entirely reduced to a univariate salience representation. Psychophysics and the temporal properties of our signals indicate that the timing of responses encoding intensity for the sight of the hand being hit are best explained by kinematic information; the timing of those encoding intensity for facial expressions are best explained by shape information in the face. In particular, the furrowing of the eyebrows and the narrowing of the eyes of the protagonist in the movies suffice to predict both the rating of and the timing of the neuronal response to the facial expressions. Comparing the broadband activity in the iEEG signal with spiking activity and an fMRI experiment with similar stimuli revealed a consistent spatial organization for the representation of intensity from our hand stimuli, with stronger intensity representation more anteriorly and around neurons with intensity coding. In contrast, for the facial expressions, we found that the activity at the three levels of measurement do not coincide, suggesting a more disorganized representation. Together, our intracranial recordings indicate that the insula encodes, in a partially intermixed layout, both static and dynamic cues from different body parts that reflect the intensity of pain experienced by others.

neuroscience↗

bioRxiv2021

Expansion of cortical layers 2 and 3 in human left temporal cortex associates with verbal intelligence

The expansion of supragranular cortical layers is thought to have enabled evolutionary development of human cognition and language. However, whether increased volume of supragranular cortical layers can actually support greater cognitive and language abilities in humans has not been demonstrated. Here, we find that subjects with higher general and verbal intelligence test (VIQ) scores have selectively expanded layers 2 and 3 only in the left temporal cortex, an area associated with language and IQ-test performance. This expansion is accompanied by lower neuron densities and larger cell-body size. Furthermore, individuals with higher VIQ scores had neurons with larger dendritic trees in left temporal cortex, potentially impacting their function. Indeed, neurons of subjects with higher VIQ scores had faster action potential upstroke kinetics, which improves information processing. These data show that expansion of supragranular layer volume, cortical and cellular micro-architecture and function are associated with improved verbal mental ability in human subjects.

neuroscience↗

bioRxiv2021

Neuronal morphology and physiology, functional brain networks and memory in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) patients are at risk of memory deficits, which have been linked to functional network disturbances, particularly of integration of the default mode network (DMN). However, the cellular substrates of functional network integration are unknown. We leverage a unique cross-scale dataset of therapy-resistant TLE patients, who underwent fMRI, MEG and/or neuropsychological testing before neurosurgery. fMRI and MEG underwent atlas-based connectivity analyses. Functional network centrality of the lateral middle temporal gyrus, part of the DMN, was used as a measure of local network integration. Subsequently, non-pathological cortical tissue from this region was used for single cell morphological and electrophysiological patch-clamp analysis, assessing integration in terms of total dendritic length and action potential rise speed. As could be hypothesized, greater network centrality related to better memory performance. Moreover, greater network centrality correlated with more integrative properties at the cellular level across patients. We conclude that individual differences in cognitively relevant functional network integration of a DMN region are mirrored by differences in cellular integrative properties of this region in TLE patients. These findings connect previously separate scales of investigation, increasing translational insight into focal pathology and large-scale network disturbances in TLE.

neuroscience↗

bioRxiv2020

Human hippocampal neurons track moments in a sequence of events.

An indispensable feature of episodic memory is our ability to temporally piece together different elements of an experience into a coherent memory. Hippocampal "time cells" - neurons that represent temporal information - may play a critical role in this process. While these cells have been repeatedly found in rodents, it is still unclear to what extent similar temporal selectivity exists in the human hippocampus. Here we show that temporal context modulates the firing activity of human hippocampal neurons during structured temporal experiences. We recorded neuronal activity in the human brain while patients learned predictable sequences of pictures. We report that human time cells fire at successive moments in this task. Furthermore, time cells also signaled inherently changing temporal contexts during empty 10-second gap periods between trials, while participants waited for the task to resume. Finally, population activity allowed for decoding temporal epoch identity, both during sequence learning and during the gap periods. These findings suggest that human hippocampal neurons could play an essential role in temporally organizing distinct moments of an experience in episodic memory. Significance StatementEpisodic memory refers to our ability to remember the "what, where, and when" of a past experience. Representing time is an important component of this form of memory. Here, we show that neurons in the human hippocampus represent temporal information. This temporal signature was observed both when participants were actively engaged in a memory task, as well as during 10s-long gaps when they were asked to wait before performing the task. Furthermore, the activity of the population of hippocampal cells allowed for decoding one temporal epoch from another. These results suggest a robust representation of time in the human hippocampus.

neuroscience↗

bioRxiv2020

Proteomic and Transcriptomic Analyses of the Hippocampus and Cortex in SUDEP and High-Risk SUDEP Cases

Sudden unexpected death in epilepsy (SUDEP) is the leading type of epilepsy-related death. Severely depressed brain activity in these cases may impair respiration, arousal, and protective reflexes, occurring as a prolonged postictal generalized EEG suppression (PGES) and resulting in a high-risk for SUDEP. In autopsy hippocampus and cortex, we observed no proteomic differences between SUDEP and epilepsy cases, contrasting our previously reported robust differences between epilepsy and controls. Transcriptomics in hippocampus and cortex from surgical epilepsy cases segregated by PGES identified 55 differentially expressed genes (37 protein-coding, 15 lncRNAs, three pending) in hippocampus. Overall, the SUDEP proteome and high-risk SUDEP transcriptome largely reflected other epilepsy cases in the brain regions analyzed, consistent with diverse epilepsy syndromes and comorbidities associated with SUDEP. Thus, studies with larger cohorts and different epilepsy syndromes, as well as additional anatomic regions may identify molecular mechanisms of SUDEP.

neuroscience↗

bioRxiv2019

Theta-phase dependent neuronal coding during sequence learning in human single neurons.

The ability to maintain a sequence of items in short-term memory (STM) is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human subjects learned sequences of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining their sequential order in STM.

neuroscience↗

bioRxiv2018

A cellular basis of human intelligence

It is generally assumed that human intelligence relies on efficient processing by neurons in our brain. Behavioral and brain-imaging studies robustly show that higher intelligence associates with faster reaction times and thicker gray matter in temporal and frontal cortical areas. However, no direct evidence exists that links individual neuron activity and structure to human intelligence. Since a large part of cortical grey matter consists of dendrites, these structures likely determine cortical architecture. In addition, dendrites strongly affect functional properties of neurons, including action potential speed. Thereby, dendritic size and action potential firing may constitute variation in cortical thickness, processing speed, and ultimately IQ.\n\nTo investigate this, we took advantage of brain tissue available from neurosurgery and recorded from pyramidal neurons in the medial temporal cortex, an area showing high association between cortical thickness, cortical activity and intelligence. Next, we reconstructed full dendritic structures of recorded neurons and combined these with brain-imaging data and IQ scores from the same subjects. We find that high IQ scores and large temporal cortical thickness associate with larger, more complex dendrites of human pyramidal neurons. We show in silico that larger dendrites enable pyramidal neurons to track activity of synaptic inputs with higher temporal precision, due to fast action potential initiation. Finally, we find that human pyramidal neurons of individuals with higher IQ scores sustain faster action potentials during repeated firing. These findings provide first evidence that human intelligence is associated with neuronal complexity, action potential speed and efficient information transfer in cortical neurons.

neuroscience↗