Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex

PLoS Biology, Sep 2008

Synaptic interactions between neurons of the human cerebral cortex were not directly studied to date. We recorded the first dataset, to our knowledge, on the synaptic effect of identified human pyramidal cells on various types of postsynaptic neurons and reveal complex events triggered by individual action potentials in the human neocortical network. Brain slices were prepared from nonpathological samples of cortex that had to be removed for the surgical treatment of brain areas beneath association cortices of 58 patients aged 18 to 73 y. Simultaneous triple and quadruple whole-cell patch clamp recordings were performed testing mono- and polysynaptic potentials in target neurons following a single action potential fired by layer 2/3 pyramidal cells, and the temporal structure of events and underlying mechanisms were analyzed. In addition to monosynaptic postsynaptic potentials, individual action potentials in presynaptic pyramidal cells initiated long-lasting (37 ± 17 ms) sequences of events in the network lasting an order of magnitude longer than detected previously in other species. These event series were composed of specifically alternating glutamatergic and GABAergic postsynaptic potentials and required selective spike-to-spike coupling from pyramidal cells to GABAergic interneurons producing concomitant inhibitory as well as excitatory feed-forward action of GABA. Single action potentials of human neurons are sufficient to recruit Hebbian-like neuronal assemblies that are proposed to participate in cognitive processes.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

http://www.plosbiology.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371/journal.pbio.0060222&representation=PDF

Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex

Citation: Molnar G, Olah S, Komlosi G, Fule M, Szabadics J, et al. ( Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex Ga bor Moln ar 0 1 Szabolcs Ol ah 0 1 Gergely Komlo si 0 1 Miklo s Fu le 0 1 J anos Szabadics 0 1 Csaba Varga 0 1 Pa l Barz o 0 1 Ga bor Tam as 0 1 0 Academic Editor: Rafael Yuste, Columbia University , United States of America 1 1 Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary, 2 Department of Neurosurgery, University of Szeged , Szeged , Hungary Synaptic interactions between neurons of the human cerebral cortex were not directly studied to date. We recorded the first dataset, to our knowledge, on the synaptic effect of identified human pyramidal cells on various types of postsynaptic neurons and reveal complex events triggered by individual action potentials in the human neocortical network. Brain slices were prepared from nonpathological samples of cortex that had to be removed for the surgical treatment of brain areas beneath association cortices of 58 patients aged 18 to 73 y. Simultaneous triple and quadruple whole-cell patch clamp recordings were performed testing mono- and polysynaptic potentials in target neurons following a single action potential fired by layer 2/3 pyramidal cells, and the temporal structure of events and underlying mechanisms were analyzed. In addition to monosynaptic postsynaptic potentials, individual action potentials in presynaptic pyramidal cells initiated long-lasting (37 6 17 ms) sequences of events in the network lasting an order of magnitude longer than detected previously in other species. These event series were composed of specifically alternating glutamatergic and GABAergic postsynaptic potentials and required selective spike-to-spike coupling from pyramidal cells to GABAergic interneurons producing concomitant inhibitory as well as excitatory feedforward action of GABA. Single action potentials of human neurons are sufficient to recruit Hebbian-like neuronal assemblies that are proposed to participate in cognitive processes. - Functional characterization of microcircuits of the cerebral cortex of rodents, carnivores, and to some extent, monkeys has been propelled by simultaneous multiple recordings from synaptically connected neurons combined with anatomical and molecular analysis of the recorded cells providing direct experimental analysis of neural connections [15]. In the human cortical microcircuit, however, only single cells were characterized to date; interactions between identified neurons were not studied [68]. Recent in vivo experiments in rodents showed that individual neurons of the cerebral cortex can effectively initiate movements [9] and modulate behavioral tasks [10]. This suggests that the activity of a single cell is sufficient for driving a relatively widespread functional assembly of neurons. However, mechanisms at the level of microcircuits are not clear in producing single-neurontriggered events requiring the activation of neural assemblies originally postulated to be important in higher order brain functions by Hebb [11]. Feed-forward excitatory and inhibitory connections are required for wiring spike and signal propagation in neural circuits and were proposed to participate in sculpting the pattern of firing traveling through the network [1120]. Experiments testing the effectiveness of individual pyramidal neurons of the cortex showed excitatory, but usually subthreshold, postsynaptic potentials and occasional triggering of postsynaptic spikes in interneurons, leading to temporally limited (,3 ms) microcircuit events terminated by disynaptic inhibitory responses [2,18,2123]. Thus, it is considered that single presynaptic spikes in pyramidal cells are not sufficient for initiating postsynaptic firing in glutamatergic neurons [24], and effective triggering of subsequent multistep event sequences characteristic to functional neuronal assemblies requires concomitant activation of several convergent inputs or repeated firing of single presynaptic cells. We set out to record the first interactions between identified human pyramidal cells and their postsynaptic target neurons in order to characterize the saliency of single cells and the contribution of unitary signals to the triggering of compound network events. Our recordings reveal that single spikes of pyramidal neurons are followed, not only by monosynaptic excitatory postsynaptic potentials (EPSPs), but also by complex event sequences with a stereotyped series of polysynaptic potentials. We then show some of the underlying network mechanisms that sequentially combine the pathwayspecific effectiveness of glutamatergic excitation followed by a concomitant and bimodal GABAergic wave of events composed of inhibitory and excitatory effects. We recorded the first connections, to our knowledge, between human nerve cells and reveal (...truncated)


This is a preview of a remote PDF: http://www.plosbiology.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371/journal.pbio.0060222&representation=PDF

Gábor Molnár, Szabolcs Oláh, Gergely Komlósi, Miklós Füle, János Szabadics, Csaba Varga, Pál Barzó, Gábor Tamás. Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex, PLoS Biology, 2008, 9, DOI: 10.1371/journal.pbio.0060222