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.
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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)