Human Ex Vivo Cortical Microcircuit: Identified Connections, Inhibitory Control and Neuromodulation

Cortical computational capability processes arise from the interaction among synaptic transmission, cellular excitability, dendritic integration, inhibitory regulation, plasticity, neuromodulation, network architecture, and the extracellular environment. Although each has been studied in depth, yet largely in isolation or without direct identification of the participating cell types and connections. Plasticity rules are established at single connections without reference to the inhibitory circuitry that constrains them, while neuromodulation is characterised at the receptor level without a corresponding account of what it does to the local network. Ex vivo cortical preparations offer the possibility of integrating these levels by allowing the simultaneous recording of neurons identified morphologically, physiologically or molecularly, while preserving the local circuit architecture. Surgically resected human cortical tissue is particularly important because it allows for the direct study of cellular and synaptic mechanisms in the human brain, in known layers and known cell types, and in which pharmacological agents can be applied directly. Recent findings from work in resected human cortex has demonstrated that many of the cellular and biophysical properties observed in rodent models are not present in the same form in the microcircuitry of the human cerebral cortex, highlighting the need to distinguish conserved mechanisms from human specializations.This Research Topic aims to assemble mechanistic studies that resolve cortical synaptic function at the level of identified cells, synaptic connections, and local microcircuits, with a primary emphasis on surgically resected human cortical tissue. We welcome work addressing unitary synaptic transmission and plasticity at identified cortical synapses, dendritic and axonal signal integration, cell-type-specific inhibitory control, and neuromodulatory regulation of synaptic transmission and circuit state; the contribution of interneuron subtypes to the balance of excitation and inhibition; tonic and phasic inhibitory signaling; and the neuromodulatory control of transmission and local circuit state, including receptor pharmacology and the testing of compounds on living tissue. Comparative studies using acute and organotypic slices, cultured cortical networks and surgically resected human tissue are all in scope, when they directly inform the interpretation of human cortical mechanisms. Where authors can set their findings against data from another species, we encourage them to do so, since the question of which cortical mechanisms are conserved and which are species-specific remains open. That comparison is welcome throughout, but it is not a condition of submission.We invite contributions spanning synaptic, cellular, circuit and translational research that resolves mechanism at identified connections or at microcircuit resolution in cortical preparations. Topics of interest include, but are not limited to:• Unitary synaptic transmission and short or long-term potentiation and depression at identified cortical synapses• Plasticity of excitatory and inhibitory connections and its layer and cell-type specificity• Contributions of interneuron subtypes to excitation and inhibition balance• Tonic and phasic and slow inhibition, including extrasynaptic and metabotropic receptor signaling• State dependent neuromodulation of synaptic transmission and local circuit state• Dendritic and axonal integration, signal propagation, calcium dynamics and biophysical scaling in cortical neurons• Receptor pharmacology and compound testing on living cortical tissue• Effects of age, clinical condition, tissue origin, epilepsy, and other pathological conditions on identified cortical cells and connection• Species differences in synaptic efficacy, kinetics and connectivity across cortical preparations• Methods for obtaining, maintaining and assessing acute, organotypic and human ex vivo cortical tissue• Advanced methodologies (paired and multiple patch-clamp recordings, dynamic clamp, optogenetics, patch-seq and single-cell omics, morphological reconstruction) applied to address defined microcircuit mechanismsWe encourage a wide range of submissions, including original research, methods papers, brief research reports, data reports, systematic reviews, mini reviews and perspectives. Topic editors: Gabor Molnar, Lucia Wittner, Brian R Lee Source: https://www.frontiersin.org/research-topics/86217/human-ex-vivo-cortical-microcircuit-identified-connections-inhibitory-control-and-neuromodulation