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. We recorded the first connections, to our knowledge, between human nerve cells and reveal that a subset of interactions is so strong that some presynaptic cells are capable of eliciting action potentials in the postsynaptic target neurons. Interestingly, these strong connections selectively link pyramidal cells using the neurotransmitter glutamate to neurons releasing gamma aminobutyric acid (GABA). Moreover, the GABAergic neurons receiving the strong connections include different types: basket cells, which inhibit several target cell populations, and another type called the chandelier cells, which can be excitatory and target pyramidal cells only. Thus, the activation originating from a single pyramidal cell propagates to synchronously working inhibitory and excitatory GABAergic neurons. Inhibition then arrives to various neuron classes, but excitation finds only pyramidal cells, which in turn, can propagate excitation even further in the network of neurons. This chain of events revealed here leads to network activation approximately an order of magnitude longer than detected previously in response to a single action potential in a single neuron. Individual-neuron–activated groups of neurons resemble the so-called functional assemblies that were proposed as building blocks of higher order cognitive representations.

While oncotherapy has made rapid progress in recent years, side effects of anti-cancer drugs and treatments have also come to the fore. These side effects include cardiotoxicity, which can cause irreversible cardiac damages with long-term morbidity and mortality. Despite the continuous in-depth research on anti-cancer drugs, an improved knowledge of the underlying mechanisms of cardiotoxicity are necessary for early detection and management of cardiac risk. Although most reviews focus on the cardiotoxic effect of a specific individual chemotherapeutic agent, the aim of our review is to provide comprehensive insight into various agents that induced cardiotoxicity and their underlying mechanisms. Characterization of these mechanisms are underpinned by research on animal models and clinical studies. In order to gain insight into these complex mechanisms, we emphasize the role of inflammatory processes and oxidative stress on chemotherapy-induced cardiac changes. A better understanding and identification of the interplay between chemotherapy and inflammatory/oxidative processes hold some promise to prevent or at least mitigate cardiotoxicity-associated morbidity and mortality among cancer survivors.