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Holtkamp, M.

Publications and source records attributed to Holtkamp, M..

3 recordsLinked to original sources

Intra-individual Physiomic Landscape of Pyramidal Neurons in the Human Neocortex

Understanding the functional principles of the human brain requires deep insight into the neuronal and network physiology. To what extent such principles of cellular physiology and synaptic interactions are common across different human individuals is unknown. We characterized the physiology of ~1200 pyramidal neurons and ~1400 monosynaptic connections using advanced multineuron patch-clamp recordings in slices from human temporal cortex. To disentangle within and between individual sources of heterogeneity, we recorded up to 100 neurons per single subject. We found that neuronal, but not synaptic physiology varied with laminar depth. Connection probability was ~15% throughout layer 2-3. Synaptic amplitudes exhibited heavy-tailed distributions with an inverse power law relationship to short term plasticity. Neurons could be classified into four functional subtypes. These general principles of microcircuit physiology were common across individuals. Our study advances the understanding of human neuron and synaptic diversity from an individual and phenotypic perspective.

neuroscience↗

Early beta oscillations in multisensory association areas underlie crossmodal performance enhancement

The combination of signals from different sensory modalities can enhance perception and facilitate behavioral responses. While previous research described crossmodal influences in a wide range of tasks, it remains unclear how such influences drive performance enhancements. In particular, the neural mechanisms underlying performance-relevant crossmodal influences, as well as the latency and spatial profile of such influences are not well understood. Here, we examined data from high-density electroencephalography (N = 30) and electrocorticography (N = 4) recordings to characterize the oscillatory signatures of crossmodal facilitation of response speed, as manifested in the speeding of visual responses by concurrent task-irrelevant auditory information. Using a data-driven analysis approach, we found that individual gains in response speed correlated with reduced beta power (13-25 Hz) in the audiovisual compared with the visual condition, starting within 80 ms after stimulus onset in multisensory association and secondary visual areas. In addition, the electrocorticography data revealed a beta power suppression in audiovisual compared with visual trials in the superior temporal gyrus (STG). Our data suggest that the crossmodal facilitation of response speed is associated with early beta power in multisensory association and secondary visual areas, presumably reflecting the enhancement of early sensory processing through selective attention. This finding furthers our understanding of the neural correlates underlying crossmodal response speed facilitation and highlights the critical role of beta oscillations in mediating behaviorally relevant audiovisual processing. Significance StatementThe use of complementary information across multiple senses can enhance perception. Previous research established a central role of neuronal oscillations in multisensory perception, but it remains poorly understood how they relate to multisensory performance enhancement. To address this question, we recorded electrophysiological signals from scalp and intracranial electrodes (implanted for presurgical monitoring) in response to simple visual and audiovisual stimuli. We then associated the difference in oscillatory power between the two conditions with the speeding of responses in the audiovisual trials. We demonstrate, that the crossmodal facilitation of response speed is associated with beta power in multisensory association areas during early stages of sensory processing. This finding highlights the importance of beta oscillations in mediating behaviorally relevant audiovisual processing.

neuroscience↗

Lithium inhibits tryptophan catabolism via the inflammation-induced kynurenine pathway in human microglia

Activation of the kynurenine pathway may lead to depletion of the serotonin precursor tryptophan, which has been implicated in the neurobiology of depression. This study describes a mechanism whereby lithium inhibits inflammatory tryptophan breakdown. Upon activation, immortalized human microglia showed a robust increase in indoleamine-2,3-dioxygenase (IDO1) mRNA transcription, IDO1 protein expression, and activity. Further, chromatin immunoprecipitation verified enriched binding of both STAT1 and STAT3 to the IDO1 promoter. Lithium counteracted these effects, increasing inhibitory GSK3{beta}S9 phosphorylation and reducing STAT1S727 and STAT3Y705 phosphorylation levels in activated cells. Experiments in primary human microglia and human induced pluripotent stem cell (hiPSC)-derived microglia corroborated lithiums effects. Moreover, IDO activity was reduced by GSK3 inhibitor SB-216763 and STAT inhibitor nifuroxazide via downregulation of P-STAT1S727 and P-STAT3Y705. Our study demonstrates that lithium inhibits the inflammatory kynurenine pathway in the microglia compartment of the human brain.

neuroscience↗