Investigating the mechanisms of cellular and network rhythmogenesis in the hippocampal formation and neocortex

Rhythmic activity is a hallmark of neural activity on all organizational scales. On the cellular and population levels, various forms of rhythmic activity have been identified and countless studies have demonstrated the necessity of these rhythms for normal cognitive function. Here, we focus on studies of rhythmic activity in the theta (4--12 Hz) frequency band in the hippocampal formation and in the gamma (30--90 Hz) frequency band in the neocortex, as well as the development of several technological tools to further the study of these phenomena. We find that intrinsic rhythmicity of layer II stellate neurons of the entorhinal cortex develops in the third postnatal week and that the emergence of this property can be attributed to changes in passive membrane properties, expression levels of a persistent sodium conductance, and, to a lesser degree, expression levels of the hyperpolarization-activated cation conductance, Ih. We find that substantial membrane nonlinearities are introduced by these conductances and that these nonlinearities produce phase-dependent modulation of synaptic inputs during intrinsic and extrinsic oscillations of membrane potential.;In order to study the generation of these rhythms at the population level computationally, we developed software capable of simulating neuron networks and seamlessly interfacing these simulations with existing dynamic clamp software. Experimental efforts were bolstered by the construction of a two-photon laser scanning microscope that enabled calcium imaging studies and the employment of transgenic animals expressing fluorophores in genetically-identified populations for electrophysiological studies. These technologies enabled the computational and experimental study of neocortical gamma rhythmogenesis. Investigating the manner in which this rhythm arises in networks displaying high levels of variability, we found that, although rhythm generation is robust, passive membrane properties, synaptic efficacy, and noise contribute greatly to the frequency and stability of this rhythm. We further investigated these relationships in order to determine the manner in which these intrinsic cellular and synapse properties affect network-level oscillations, stability, and input sensitivity.