Gamma oscillations (30 -120 Hz) are thought to be important for various cognitive functions, including perception and working memory, and disruption of these oscillations has been implicated in brain disorders, such as schizophrenia and Alzheimer's disease. The cornu ammonis area 1 (CA1) of the hippocampus receives gamma frequency inputs from upstream regions (cornu ammonis area 3 and medial entorhinal cortex) and generates itself a faster gamma oscillation. The exact nature and origin of the intrinsic CA1 gamma oscillation is still under debate. Here, we expressed channelrhodopsin-2 under the CaMKII␣ promoter in mice and prepared hippocampal slices to produce a model of intrinsic CA1 gamma oscillations. Sinusoidal optical stimulation of CA1 at theta frequency was found to induce robust theta-nested gamma oscillations with a temporal and spatial profile similar to CA1 gamma in vivo. The results suggest the presence of a single gamma rhythm generator with a frequency range of 65-75 Hz at 32°C. Pharmacological analysis found that the oscillations depended on both AMPA and GABA A receptors. Cell-attached and whole-cell recordings revealed that excitatory neuron firing slightly preceded interneuron firing within each gamma cycle, suggesting that this intrinsic CA1 gamma oscillation is generated with a pyramidal-interneuron circuit mechanism.

Recently, we have developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserved natural extracellular matrix structure, mechanical anisotropy, and vasculature templates, and also showed good cell recellularization and differentiation potential. In this study, a multi-stimulation bioreactor was built to provide coordinated mechanical and electrical stimulations for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (106 cells/ml) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that, after 2-day culture with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed cardiomyocyte-like phenotype, by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2-day bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2-day and 4-day tissue constructs were comparable to the tissue constructs produced by stirring reseeding followed by 2-week static culture, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development, but also for patients by reducing the waiting time in future clinical scenarios.

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The entorhinal-hippocampal system is an important circuit in the brain, essential for certain cognitive tasks such as memory and navigation. Different gamma oscillations occur in this circuit, with the medial entorhinal cortex (mEC), CA3 and CA1 all generating gamma oscillations with different properties. These three gamma oscillations converge within CA1, where much work has gone into trying to isolate them from each other. Here, we compared the gamma generators in the mEC, CA3 and CA1 using optogenetically induced theta-gamma oscillations. Expressing channelrhodopsin-2 in principal neurons in each of the three regions allowed for the induction of gamma oscillations via sinusoidal blue light stimulation at theta frequency. Recording the oscillations in CA1 in vivo, we found that CA3 stimulation induced slower gamma oscillations than CA1 stimulation, matching in vivo reports of spontaneous CA3 and CA1 gamma oscillations. In brain slices ex vivo, optogenetic stimulation of CA3 induced slower gamma oscillations than stimulation of either mEC or CA1, whose gamma oscillations were of similar frequency. All three gamma oscillations had a current sink-source pair between the perisomatic and dendritic layers of the same region. Taking advantage of this model to analyse gamma frequency mechanisms in slice, we showed using pharmacology that all three gamma oscillations were dependent on the same types of synaptic receptor, being abolished by blockade of either type A c-aminobutyric acid receptors or a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors, and insensitive to blockade of N-methyl-D-aspartate receptors. These results indicate that a fast excitatory-inhibitory feedback loop underlies the generation of gamma oscillations in all three regions.

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