The oscillatory activities form neural networks are involved in many behaviors, and animals need to be able to control the frequencies of these activities to respond to the environmental challenges. Neurons in many systems have frequency-dependent properties and preferred frequencies (also known as resonance). We hypothesize that the activity frequency of an oscillatory network is determined by the preferred frequencies of the neurons and of the synapses in the network. We examined this hypothesis by investigating the frequency-dependent properties of the neurons and of the synapses in the pyloric network in the crab Cancer borealis. We also examined what factors affect the preferred frequencies and how changing in these factors influence the frequency of the network activity. We first showed that the preferred frequency of neurons could be measured with the voltage-clamp technique. Measuring the preferred frequency with the voltage-clamp technique allowed us to have a full control of the voltage range and the waveform of the oscillation. By shifting the voltage range of the oscillation, we found that the pacemaker PD neuron has a higher preferred frequency when it is oscillating at a higher voltage range, and the preferred frequency of the follower LP neuron is only affected by the upper bound of the oscillation. The PD neuron also has different preferred frequencies when oscillating with different waveforms. Specifically, one waveform parameter, the 75 - 100% rising slope, showed a negative correlation with the preferred frequency. After knowing that the voltage range and the waveform of the oscillation are correlated with the preferred frequency, we used dynamic clamp to alter the voltage range and the waveform of the PD oscillation during the ongoing activity and measured the pyloric frequency. Based on our hypothesis, we expected the voltage range and the waveform would have similar effects on the pyloric frequency as they do on the preferred frequency. Indeed, our result showed that the shifts in the pyloric frequency during the dynamic clamp experiments could be explained by the changes in the voltage range and in the waveform parameters. Finally, we examined the frequency-dependencies of the amplitude and the phase of the synaptic current. The amplitudes of the synaptic currents between the AB/PD and LP neuron showed preferred frequencies. Interestingly, the preferred frequencies of the synapses were significantly lower than those of the presynaptic neurons and also than the pyloric frequency. While the voltage range of the presynaptic PD oscillation did not affect the preferred frequency of the AB/PD to LP synapse, the preferred frequency of the LP to PD synapse was higher when the upper bound, but not the lower bound, of the LP oscillation was increased. Moreover, the strength of the synaptic resonance depended on the upper bound of the presynaptic oscillation. To produce the strongest resonance, the upper bound of the presynaptic oscillation need to be within the voltage range at which the synapse is most sensitive to the presynaptic membrane potential. In addition to the amplitude, the phase of the synapses also showed frequency-dependence. At low frequencies (< 1 Hz), the synaptic current reached its peak before the presynaptic membrane potential did, and this phase relationship reversed at high frequencies (> 1 Hz). Overall, in this study, we demonstrated that many properties of the neurons and synapses depend on the frequency of the oscillation and have preferred frequencies. Moreover, these preferred frequencies can be regulated by many factors, including the voltage range and the waveform of the oscillation. Because some of these frequency-dependent properties are able to influence the network frequency, the factors affecting their preferred frequencies could change the network frequency in the same way. As a result, the frequency of an oscillatory network is not determined by a single factor, but by the dynamic interactions among the frequency-dependent properties of the network components.
This dissertation investigated how several different types of oscillation organize neural activity in the hippocampus and the entorhinal cortex. I used recordings performed by myself and others to explore the nature of the ripple, sharp wave, fast gamma, theta, and spindle oscillations, the manner in which these oscillations propagate through the hippocampal network, and how behavior affects the properties of these oscillations. The first study concerned two types of high frequencyoscillation in CA1: fast gamma and ripples, their relationship to sharp waves, the nature of their emergence in CA3 and propagation to CA1, and their interaction with slow oscillations during sleep. I found that the ripple oscillation emerges de novo in CA1 rather than being transmitted wave-by-wave from CA3 to CA1. I also found that there is an inverted-U shaped relationship between the peak frequency of ripple oscillations and the amplitude of sharp waves. The second study extended the observations of the first study by taking the behavioral state of the animal into account. I found that the ripples that occur intermidst active behavior oscillate at a higher frequency than those that occur during sleep and quiescence, and that the relationship between sharp wave amplitude and ripple frequency differs depending on behavioral state. I also found that ripples that are detected during running are due to recording artifacts, whereas ripples occasionally occur during REM sleep. The third study examined the nature of sleep spindles in the hippocampus, and is an exploration (and ultimately, a rejection) of the hypothesis that the mechanisms of sleep spindles are the same. I found that many neurons prefer different oscillation phases of theta and spindles, suggesting that different sets of inputs drive neurons. I also found that principal cells are not rhythmically entrained by spindle oscillations; this and the lack of phase precession during spindles led to the conclusion that spindles should not be considered as a special case of theta.
Apparent but controversial evidence of supersolidity, a coexistence of crystalline and superfluid states, was observed in 2004. Samples of solid 4He were grown, in a chamber, inside a torsion oscillator (TO). The samples showed evidence of apparent decoupling from their container in the form of a resonant frequency increase of the TO as the temperature was lowered. We have developed a Compound torsion oscillator (CTO), with two resonant modes, that allows us to observe a single solid helium sample at two frequencies simultaneously. This thesis will cover the first comprehensive study on the frequency dependence of the apparent supersolid effect. This includes a study of the effect of varying 3He concentrations (x3) on the frequency dependence. Additionally a study on how changes in x3 affect the dissipation, which previous studies of x3 dependence have not explored. Also studied is how varying x3 affected the hysteresis first observed by Aoki et al. The CTO has allowed the exploration of the amplitude dependent effects in new ways. By exciting the sample at both frequencies simultaneously and varying the driving amplitude of one mode one can see how excitations at one mode affect what is observed at the other. The studies of the effects of varying x3 show results that are consistent with the dislocation movement model proposed by Iwasa. The collected data was not consistent with the simple supersolid model initially proposed. The studies of hysteresis show that the onset of hysteresis was dependent on x3 but was not frequency dependent. This lends credit to the hysteresis being due to the pinning and unpinning of 3He impurities. The studies of the effect of amplitude dependent effects show an asymmetry between the two frequencies. The higher frequency has a larger effect on the lower frequency than the lower frequency has on the higher. This is also inconsistent with the initial simple supersolid model.
Frequency synthesizers are widely being used for generating local oscillators for majority of RF, wireless, communication, and navigation systems for the last few decades. Phase-locked-loops (PLL) on the other hand are one of the fundamental portions of any digital/mixed-signal devices in addition to the previously mentioned systems. In this thesis work, a PLL based fractional-N frequency synthesizer for 2.4 GHz and 5 GHz wireless local area network (WLAN) in 0.18 μm CMOS-RF process has been proposed. With the adoption of a MASH 1-1-1 delta-sigma modulator facilitating fractional division ratios through a programmable divider, the frequency synthesizer differs from its integer-N counterpart in its higher reference frequency, wider loop bandwidth, faster settling time, and better phase noise and suppression of spurious tones. The synthesizer consists of several blocks, including a wide range LC-tuned voltage controlled oscillator (VCO), divide by 16 – 252 programmable divider, dead-zone free phase-frequency detector (PFD), low mismatch high swing cascode charge pump (CP), 3rd order loop filter (LF), and a 3rd order MASH delta-sigma modulator (DSM)—all of which have been designed and constructed in both transistor and layout levels. SPICE (BSIM3) level simulations have been performed for all the individual blocks as well as the complete frequency synthesizer for extracting transient, DC, periodic-steady-state, and phase-noise analyses results. Overall, with 1.2 V supply voltage, the 0.628 mm X 0.594 mm fractional-N frequency synthesizer achieves “locked” state in approximately 2 μs and produces approximately -111 dBc/Hz phase noise at 1 MHz offset (excluding the MASH modulator) while consuming about 20.76 mW of power.
The 24-hour biological rhythm, or circadian rhythm, has been attributed as a fitness trait in multiple organisms.  To identify how organisms adapted their circadian rhythms to increase their fitness, we used a global population from the Neurospora discreta complex. Under cycling light conditions, North American strains in N. discreta PS4B exhibit no rhythms in their sporulation output. To understand the molecular variation of the oscillator underlying these divergent phenotypes, we analyzed the expression of the key clock protein FREQUENCY and found FRQ levels have a rhythm in constant conditions. Based on our findings, we concluded that the North American strains in the N. discreta PS4B population have decoupled their developmental rhythm from their molecular oscillator to enhance their fitness. Our mathematical model supports the hypothesis that North American strains have increased their fitness by decreasing their coupling coefficient and threshold. In addition, we found the candidate region for habitat specific clock variation (HSCV) occurs on chromosome 3. In an intercontinental F1 population, we observed an opposite allele effect, resulting in strains with the North American phenotype having the African parent allele. To understand the mechanism and components of another oscillator, we used the strain PRD-1, which is hypothesized in the literature to be a key component of the metabolic oscillator. We have observed arrhythmic ATP oscillation in PRD-1 compared to WT strains.
Circadian rhythms are daily oscillations in biological activities that have a periodicity of approximately 24 hours. Underlying these rhythms are multiple molecularoscillators that interact to form the circadian clock of an organism. The filamentous fungi and eukaryotic model organism, Neurospora crassa, possesses a core circadian oscillator known as the FREQUENCY (FRQ)/WHITE-COLLAR (WC) oscillator (FWO). Recent studies have shown that homologous Neurospora clock genes are not universally conserved across the fungal kingdom. Here, we aimed to identify similaritiesand differences at the sequence, molecular, and macroscopic level of the circadian clock in divergently related species to N. crassa. The Neurospora discreta species complex contains numerous reproductive species with isolates that have been collected from allaround the world, and extend the latitudinal boundaries of Neurospora by inhabiting regions as far North as Alaska, thus this clade provides an unique opportunity to study the evolution of the fungal clock to diverse local environments. Sequence comparison of the Neurospora discreta PS4b (8579) core clock homologs revealed a high degree of overall conservation with notable exceptions in the presence of additional WC complex consensus binding sites in frequency, suggesting possible differences in gene expression.Rhythms in asexual development in Neurospora discreta sensu stricto are overtly circadian regulated and underlying this were oscillations in FRQ abundance and phosphorylation were robust. Rhythmic conidiation in N. discreta PS4b 8579 was observed in cycling and free-running environments, however this expression was reliant upon several environmental conditions in order to be visualized. Molecular analysis of FRQ appears to reveal rhythms in abundance with decreased amplitude. An Alaskan strain, N. discreta PS4b 9981, demonstrated blue light mediated photo-responses, but was arrhythmic under free-running conditions and temperature cycling conditions. Phenotypes in asexual development of N. discreta species range from robustly clock controlled to arrhythmic. Western analysis of FRQ in N. discreta sensu stricto and N. discreta PS4b 8579, suggests that these phenotypes might reflect differences in the FWO.Based on data from the current study, we propose that these changes in clock regulation might have played a role for the N. discreta species to adapt to their local environments.
In the current study, we have tested the hypothesis that temperature compensation (TC) of the circadian clock plays a role in local adaptation. To test this hypothesis, we chose strains of Neurospora collected from different latitudes; Alaska (high) and Ivory Coast (low). To examine the molecular oscillator of these selected strains, we transformed the natural strains with a translational luciferase reporter of the key clock gene FREQUENCY (FRQ). To examine the developmental overt rhythm, we used the inverted race tube assay. Q10 values of the molecular periods and the developmental periods of each strain have been calculated, and used as a quantitative measure of TC. Our data suggest that the molecular oscillators of natural strains collected from different latitudes do not differ from one another, and their Q10 values are relatively similar to each other. However, we found that the developmental overt rhythms have different period and Q10 values and a period among the strains studied. The periods and Q10 values of developmental rhythm are also more variable when compared to those of the molecular rhythm. Taken our results together, we concluded that 1) TC plays a role in adaptation, 2) the adaptation occurred at either the output of the clock or at the coupling mechanism between the oscillator, and 3) the adaptation occurred at the developmental rhythm rather than the molecular oscillator
Active Inductors are useful in reducing the large chip area typically consumed by spiral inductors, as well as providing larger inductance values and higher quality factors that otherwise cannot be achieved by spiral inductors. Integrated inductors find application in many radio frequency (RF) front end integrated circuits, including impedance matching, filtering, biasing and in oscillator circuits. Nonetheless, because of the interdependent relationship of the self-resonant frequency and quality factor it is often difficult to meet desired circuit requirements. Additionally, active devices pose problems of higher power consumption , noise figure and potential instability. This thesis begins with the study of active inductors, the Wu active inductor in particular, and considers tuning methods based on the Wu active inductor topology. Starting with the small-signal model, the emulated inductance and quality factor expressions are derived. Next, the operation of active inductors under large-signal is closely examined. Comparisons between a passive and an active VCO are made. The active inductor based voltage-controlled oscillator (Active VCO) is studied extensively, and the methods of improving the performance under large signal-behavior are discussed. Then a design procedure based on gm/ID methodology is proposed. A Matlab script that can be applied to gyrator-C based active inductors is developed to determine the sizing of the transistors for a desired inductance and resonant frequency. Cadence Virtuoso is used for simulations, and extraction based on an IBM 8RF technology file. Finally, a low power active VCO is designed, simulated and laid out.
Contributors:Weinberger, Norman M., Miasnikov, Alexandre A., Bieszczad, Kasia M., Chen, Jemmy C.
Gamma oscillations (∼30-120Hz) are considered to be a reflection of coordinated neuronal activity, linked to processes underlying synaptic integration and plasticity. Increases in gamma power within the cerebral cortex have been found during many cognitive processes such as attention, learning, memory and problem solving in both humans and animals. However, the specificity of gamma to the detailed contents of memory remains largely unknown. We investigated the relationship between learning-induced increased gamma power in the primary auditory cortex (A1) and the strength of memory for acoustic frequency. Adult male rats (n=16) received three days (200 trials each) of pairing a tone (3.66 kHz) with stimulation of the nucleus basalis, which implanted a memory for acoustic frequency as assessed by associatively-induced disruption of ongoing behavior, viz., respiration. Post-training frequency generalization gradients (FGGs) revealed peaks at non-CS frequencies in 11/16 cases, likely reflecting normal variation in pre-training acoustic experiences. A stronger relationship was found between increased gamma power and the frequency with the strongest memory (peak of the difference between individual post- and pre-training FGGs) vs. behavioral responses to the CS training frequency. No such relationship was found for the theta/alpha band (4-15 Hz). These findings indicate that the strength of specific increased neuronal synchronization within primary sensory cortical fields can determine the specific contents of memory.
This thesis presents a three-dimensional numerical study on the dynamics of deformable capsules in sinusoidally oscillating shear flow. For this study, we consider capsules of spherical and oblate spheroid resting shapes. For spherical resting shapes, we find identical deformation response during positive and negative vorticity. However, the deformation response becomes unequal and shows complex behavior for nonspherical resting shapes. The average elongation is higher in the retarding phase of the shear flow than in the accelerating phase. Primarily two types of dynamics are observed for nonspherical shapes: a clockwise/counter-clockwise swinging motion in response to the altering flow direction that occurs at both high and low values of shear rate amplitudes, and a continuous/unidirectional tumbling motion that occurs at intermediate values. The unidirectional tumbling motion occurs despite the fact that the time-average vorticity is zero. Such a tumbling motion is accompanied by a continuous tank-treading motion of the membrane in the opposite direction. We obtain phase diagram that shows existence of two critical shear rates and two oscillationfrequencies. The unidirectional tumbling motion occurs in the intermediate range, and the clockwise/counter-clockwise swinging motion occurs otherwise. We also find that the dynamics is highly sensitive to the initial condition. A swinging is generally observed when the capsule is released aligned with the extensional or compressional axis of the shear flow, and a tumbling is observed otherwise. These results suggest the possibility of chaotic behavior of cells in time-dependent flows. We provide explanations of such complex dynamics by analyzing the coupling between the shape and angular oscillation and the imposed flow oscillation.