Fast Oscillations In Cortical Circuits PDF Download

The present Thesis addressed different questions concerning spontaneous oscillatory activity in the cerebral cortex, including functional comparative studies, studies of mechanisms generating this activity and the evaluation of alterations in a model of mental disability. The main technique used for this work is the recording of electrophysiological extracellular Local Field Potential signals, which mainly respond to the activity of local populations of neurons. This type of recordings was obtained both in brain slices and in vivo and was used in combination with other techniques. Single Unit recordings, which evaluate the firing properties of a single neuron, were also obtained in combination of LFP in some of the studies. In the first study, we aimed to disclose the role of persistent sodium current in controlling cortical oscillatory activity, either in the generation and maintenance of UP states in slow oscillations and the control of fast beta-gamma oscillations. Here, we saw that blocking this current with phenytoin provoked the elongation of UP states and increased firing rate of the network, while the generation of new UP states was prevented. In another study, we performed a comparison of the oscillatory activity along different cortical areas in vivo. Here, prefrontal cortex showed special features compared to primary areas, including increased firing rate and gamma oscillations, and firing patterns of single units. This study also included a measurement of the speed of propagation of UP states, because prefrontal cortex was found to present a reduced Coefficient of Variation of UP state duration, compatible with being an area of wave generation. Thus, we aimed to demonstrate a main pattern of propagation of slow waves from frontal areas to posterior areas, as previously described in humans. Finally, we performed a study of the functional and anatomical alterations in the cortical network underlying cognitive deficits in a transgenic model of Down syndrome, TgDyrk1A mice. This work was performed in two cortical areas: prefrontal and primary somatosensory cortex. In our study of prefrontal cortex, TgDyrk1A mice presented alterations in oscillatory activity that were compatible with as more inhibited network, such as decreased firing rate, decreased gamma oscillations and a slower speed of propagation. This unbalance between excitation and inhibition was later demonstrated at anatomical level, and may explain our findings of altered behavior in cognitive tasks that involved prefrontal cortex such as the puzzle box. In our study in somatosensory cortex, thalamocortical evoked potentials showed increased cortical inhibition. Although that, oscillatory activity, either in parameters of Slow waves or beta-gamma frequencies, remained unchanged, suggesting the existence of compensatory mechanisms. From the work of this Thesis, we demonstrated some mechanistic aspects that control the emergence of rhythmic patterns from cortical circuits, with a striking role on the mechanisms which control excitability or cortical connectivity that underlies oscillations. First, this study presents de dependence of slow and fast rhythms on an intrinsic mechanism of neurons that governs cortical oscillations which is the persistent sodium current. Secondly, here is presented the role of cortical excitability in the expression of those rhythms across different cortical areas. And finally, this study shows the changes in cortical network function in a model of Down syndrome by means of analyzing oscillatory activity, as this represents a network activity and reflects the altered cellular and connectivity elements which are critical for the expression of cortical rhythms. These findings can all be understood within frame of altered balance between excitation and inhibition.