Mechanisms underlying spontaneous oscillations in the hippocampus in vitro

In vivo oscillations, reflecting the coordinated activity ofneuronal ensembles, are observed spontaneously and through stimulus-driven experimentation, and have been suggested to be important for cognitive functions. This thesis has revealed the preservation of the hippocampus in the in vitro slice has sufficient endogenous drive and/or neuromodulatory substance release, to generate persistent spontaneous gamma-theta oscillations without the need for any external manipulations. In addition, hippocampal areas CAl and CA3 have the intrinsic capabilities to generate spontaneous oscillations without any external input. Spontaneous oscillations in area CA3 are inhibition-based rhythms. The time-dependent expressions of these rhythms were dependent upon NMDARs, with gamma frequency oscillation also reliant upon KAR, mGluR and AchRs. The stability ofestablished spontaneous beta and gamma frequency oscillations was reliant upon KAR, and mAchRs excitatory drives, holding some similarities to previous druginduced models. However, these spontaneous. oscillations required different excitatory transmitter systems in conjunction, suggesting they are unique in vitro hippocampal rhythms. Spontaneous theta oscillations also appeared to constitute a novel model of atropine-resistant theta rhythms, proposed to be generated via lacunosum-moleculare interneurons. A novel fmding showed the dependence of spontaneous oscillations on GlyR-mediated inhibition. In addition, this thesis discovered high concentrations of MK-801, SKF-1O,047 and PCP can induce gamma frequency oscillations in area CA3 de novo. MK-801-induced rhythmogenesis relied upon functional sigma-l receptors, but not functional NMDARs. The stability of the oscillations depended upon KAR excitatory and GABAAR inhibitory synaptic transmission, therefore exhibiting some similarities to the established spontaneous gamma frequency rhythms. In contrast, MK-801-induced gamma frequency rhythms were potentiated by mGluRI a antagonism and resistant to GlyR blockade, suggesting that, though similar, the mechanisms responsible for gamma rhythmogenesis with sigma receptor activation may be fundamentally different from those required to generate spontaneous rhythms in drug-free conditions.EThOS - Electronic Theses Online ServiceGBUnited Kingdo