Highlights d Sex-specific differences are decreased in response to longevity interventions d Many interventions, but not rapamycin, exhibit similar transcriptomic responses d Certain gene expression changes are associated with longevity across interventions d Longevity signatures may be used to discover new lifespanextending interventions

, which blocks non-quantal release at the neuromuscular junction, suppressed the effects of AChE inhibitors. Thus, accumulation of ACh is likely to be caused by non-quantal release from cholinergic terminals. We propose that non-quantal release of ACh, shown previously at the neuromuscular junction, is present in cholinergic postganglionic fibres of the rat heart in addition to quantal release.

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Optogenetics approach is used widely in neurobiology as it allows control of cellular activity with high spatial and temporal resolution. In most studies, optogenetics is used to control neuronal activity. In the present study optogenetics was used to stimulate astrocytes with the aim to modulate neuronal activity. To achieve this goal, light stimulation was applied to astrocytes expressing a version of ChR2 (ionotropic opsin) or Opto-α1AR (metabotropic opsin). Optimal optogenetic stimulation parameters were determined using patch-clamp recordings of hippocampal pyramidal neurons’ spontaneous activity in brain slices as a readout. It was determined that the greatest increase in the number of spontaneous synaptic currents was observed when astrocytes expressing ChR2(H134R) were activated by 5 s of continuous light. For the astrocytes expressing Opto-α1AR, the greatest response was observed in the pulse stimulation mode (T = 1 s, t = 100 ms). It was also observed that activation of the astrocytic Opto-a1AR but not ChR2 results in an increase of the fEPSP slope in hippocampal neurons. Based on these results, we concluded that Opto-a1AR expressed in hippocampal astrocytes provides an opportunity to modulate the long-term synaptic plasticity optogenetically, and may potentially be used to normalize the synaptic transmission and plasticity defects in a variety of neuropathological conditions, including models of Alzheimer’s disease and other neurodegenerative disorders.

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Effects of organophosphorous acetylcholinesterase inhibitor paraoxon were studied in the isolated atrial and ventricular myocardium preparations of a fish (cod), an amphibian (frog) and a mammal (rat) using the microelectrode technique. Incubation of isolated atrium with paraoxon (5 × 10(-6)-5 × 10(-5) M) caused significant reduction of action potential duration and marked slowing of sinus rhythm. These effects were abolished by muscarinic blocker atropine and therefore are caused by acetylcholine, which accumulates in the myocardium due to acetylcholinesterase inhibition even in the absence of vagal input. Hemicholinium III is a blocker of high affinity choline-uptake transporters, which are believed to mediate non-quantal release of acetylcholine from cholinergic terminals in different tissues. In the atrial myocardium of all the three studied species, hemicholinium III (10(-5) M) significantly suppressed all the effects of paraoxon. Blocker of parasympathetic ganglionic transmission hexamethonium bromide (10(-4) M) and inhibitor of vesicular acetylcholine transporters vesamicol (10(-5) M) failed to attenuate paraoxon effects. Among ventricular myocardium preparations of three species paraoxon provoked marked cholinergic effects only in frog, hemicholinium III abolished these effects effectively. We conclude that paraoxon stops degradation of acetylcholine in the myocardium and helps to reveal the effects of acetylcholine, which is continuously secreted from the cholinergic nerves in non-quantal manner. Thus, non-quantal release of acetylcholine in the heart is not specific only for mammals, but is also present in the hearts of different vertebrates.

Investigation of biochemical mechanisms underlying the long-term storage of information in nervous system is one of main problems of modern neurobiology. As a molecular basis of long-term memory, long-term changes in kinase activities, increase in the level and changes in the subunit composition of receptors in synaptic membranes, local activity of prion-like proteins, and epigenetic modifications of chromatin have been proposed. Perhaps a combination of all or of some of these factors underlies the storage of long-term memory in the brain. Many recent studies have shown an exclusively important role of atypical protein kinases (PKCζ, PKMζ, and PKCι/λ) in processes of learning, consolidation and maintenance of memory. The present review is devoted to consideration of mechanisms of transcriptional and translational control of atypical protein kinases and their roles in induction and maintenance of long-term synaptic plasticity and memory in vertebrates and invertebrates.