Phase Advances Research Articles

Phase shifts to light are altered by antagonists to neuropeptide receptors

The mammalian circadian clock in the suprachiasmatic nucleus (SCN) is a heterogeneous structure. Two key populations of cells that receive retinal input and are believed to participate in circadian responses to light are cells that contain vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP). VIP acts primarily through the VPAC2 receptor, while GRP works primarily through the BB2 receptor. Both VIP and GRP phase shift the circadian clock in a manner similar to light when applied to the SCN, both in vivo and in vitro, indicating that they are sufficient to elicit photic-like phase shifts. However, it is not known if they are necessary signals for light to elicit phase shifts. Here we test the hypothesis that GRP and VIP are necessary signaling components for the photic phase shifting of the hamster circadian clock by examining two antagonists for each of these neuropeptides. The BB2 antagonist PD176252 had no effect on light-induced delays on its own, while the BB2 antagonist RC-3095 had the unexpected effect of significantly potentiating both phase delays and advances. Neither of the VIP antagonists ([d-p-Cl-Phe6, Leu17]-VIP, or PG99-465) altered phase shifting responses to light on their own. When the BB2 antagonist PD176252 and the VPAC2 antagonist PG99-465 were delivered together to the SCN, phase delays were significantly attenuated. These results indicate that photic phase shifting requires participation of either VIP or GRP; phase shifts to light are only impaired when signalling in both pathways are inhibited. Additionally, the unexpected potentiation of light-induced phase shifts by RC-3095 should be investigated further for potential chronobiotic applications.

Activation of M1/4 receptors phase advances the hamster circadian clock during the day

The mammalian circadian clock in the suprachiasmatic nucleus (SCN) can be reset by the cholinergic agonist carbachol. In hamsters, intraSCN carbachol produces phase advances during the day. This phenomenon has previously been attributed to the muscarinic receptors, as carbachol-induced phase shifts are blocked by pretreatment with the muscarinic antagonist atropine. The SCN contains all five muscarinic receptors, leaving open the question as to which muscarinic receptors mediate these shifts. Here we test two selective muscarinic agonists, the M1/4 agonist McN-A-343 and the M2/3 agonist bethanechol, in addition to the non-selective cholinergic agonist carbachol. Consistent with previous reports, carbachol produced significant phase advances when injected to the SCN during the mid-subjective day. At the doses used here, McN-A-343, but not bethanechol, also produced significant phase shifts when injected to the SCN during the mid-subjective day. Phase shifts to McN-A-343 were as large as those produced by carbachol, suggesting that activation of the M1/4 receptors alone can fully account for the daytime phase advances produced by cholinergic agonists. Given acetylcholine’s role in arousal, and the similarity between phase advances to carbachol/McN-A-343 and to exercise and arousal manipulations, it is possible that acetylcholine may contribute to non-photic resetting of the circadian clock.

Promoter-Terminator Gene Loops Affect Alternative 3′-End Processing in Yeast

Many eukaryotic genes undergo alternative 3'-end poly(A)-site selection producing transcript isoforms with 3'-UTRs of different lengths and post-transcriptional fates. Gene loops are dynamic structures that juxtapose the 3'-ends of genes with their promoters. Several functions have been attributed to looping, including memory of recent transcriptional activity and polarity of transcription initiation. In this study, we investigated the relationship between gene loops and alternative poly(A)-site. Using the KlCYC1 gene of the yeast Kluyveromyces lactis, which includes a single promoter and two poly(A) sites separated by 394 nucleotides, we demonstrate in two yeast species the formation of alternative gene loops (L1 and L2) that juxtapose the KlCYC1 promoter with either proximal or distal 3'-end processing sites, resulting in the synthesis of short and long forms of KlCYC1 mRNA. Furthermore, synthesis of short and long mRNAs and formation of the L1 and L2 loops are growth phase-dependent. Chromatin immunoprecipitation experiments revealed that the Ssu72 RNA polymerase II carboxyl-terminal domain phosphatase, a critical determinant of looping, peaks in early log phase at the proximal poly(A) site, but as growth phase advances, it extends to the distal site. These results define a cause-and-effect relationship between gene loops and alternative poly(A) site selection that responds to different physiological signals manifested by RNA polymerase II carboxyl-terminal domain phosphorylation status.

Four of the six Drosophila rhodopsin-expressing photoreceptors can mediate circadian entrainment in low light.

Light is the major stimulus for the synchronization of circadian clocks with day-night cycles. The light-driven entrainment of the clock that controls rest-activity rhythms in Drosophila relies on different photoreceptive molecules. Cryptochrome (CRY) is expressed in most brain clock neurons, whereas six different rhodopsins (RH) are present in the light-sensing organs. The compound eye includes outer photoreceptors that express RH1 and inner photoreceptors that each express one of the four rhodopsins RH3-RH6. RH6 is also expressed in the extraretinal Hofbauer-Buchner eyelet, whereas RH2 is only found in the ocelli. In low light, the synchronization of behavioral rhythms relies on either CRY or the canonical rhodopsin phototransduction pathway, which requires the phospholipase C-β encoded by norpA (no receptor potential A). We used norpA(P24) cry(02) double mutants that are circadianly blind in low light and restored NORPA function in each of the six types of photoreceptors, defined as expressing a particular rhodopsin. We first show that the NORPA pathway is less efficient than CRY for synchronizing rest-activity rhythms with delayed light-dark cycles but is important for proper phasing, whereas the two light-sensing pathways can mediate efficient adjustments to phase advances. Four of the six rhodopsin-expressing photoreceptors can mediate circadian entrainment, and all are more efficient for advancing than for delaying the behavioral clock. In contrast, neither RH5-expressing retinal photoreceptors nor RH2-expressing ocellar photoreceptors are sufficient to mediate synchronization through the NORPA pathway. Our results thus reveal different contributions of rhodopsin-expressing photoreceptors and suggest the existence of several circuits for rhodopsin-dependent circadian entrainment. J. Comp. Neurol. 524:2828-2844, 2016. © 2016 Wiley Periodicals, Inc.

Advances in experimental phasing.

Advances in experimental phasing.

Short Blue Light Pulses (30 Min.) in the Morning are Able to Phase Advance the Rhythm of Melatonin in a Home Setting

It is known that light in the morning is able to induce phase advances of the endogenous clock, however most studies have tested the phase advances in highly controlled laboratory conditions. At home the environmental lighting is more variable. In theory, a high intensity short morning-light pulse in the short-wavelengths-range (blue light) should be capable of inducing phase advances. If this is also true in a home setting, this could be a firm basis supporting light treatment in late chronotypes who suffer from a late sleep phase. In a study carried out in summer, 11 normal to relatively late (habitual midsleep 4:15-6:09 hours) chronotypes (age range 23-27 years, 4f/7m) participated in two conditions: (1) 1 baseline day followed by 3 consecutive days of 30 min. blue morning-light pulses, (2) 1 baseline day followed by 3 consecutive days of 60 min. blue light pulses. Blue light was applied by use of the Philips GoLite BLU (HF3320, blue leds, intensity at the cornea 2306 melanopic-lux, 300 lux, 3.65 W/m2). During all four evenings, subjects were asked to protect themselves from light exposure (<10 lux). The response of the melatonin rhythm, calculated as a shift in dim light melatonin onset (DLMO), to a single 30 min. light pulse varied between subjects and resulted in a non-significant phase advance of 15 (±48) min. (t10 = 1.04; P = 0.33), and a significant advance of 30 (±41) min. to a single 60 min. light pulse. (t10 = 2.40; P < 0.05). After 3 days of light exposure both in the 30- and in the 60 min. light pulses condition significant phase advances of DLMO were observed; 49 (±58) min. (t10 = 2.80; P < 0.05) and 59 (±29) min. (t10 = 6.9; P < 0.001) respectively. No significant differences were found in the DLMO shifts between conditions. In addition there was a trend for a lower sleepiness score directly after waking up after using light for 3 days in both conditions (t10 = 3.38; P = 0.096, 60 min. and (t10 = 4.10; P = 0.070, 30 min.). A prelimin.ary analysis of actimetry data indicated some support for an effect on sleep timin.g. The data support the conclusion that light pulses of 30 min. in the morning on three consecutive days, in a home setting, in combination with dim light during the evenings, can be part of an efficient phase advancing chronotherapy protocol.

6-h advances alter circadian activity patterns, fasting glucose, and insulin levels in C57BL6/J mice

Chronobiological disruptions, including shift work, have been linked to a number of disorders such as fatigue and diabetes. Additionally, there is evidence to support that exercise cannot only counteract fatigue and the onset of diabetes, but also alleviate the other negative symptoms associated with shift work. Therefore, the present study investigated the effects of wheel running and monthly 6-h phase advances on the circadian locomotor activity patterns and glucose and insulin levels in C57BL6/J mice. 6-h phase advances produced decreases in fasting glucose and increases in insulin, and wheel-running was able to alleviate the spike in insulin secretion. Additionally, mice experiencing the shift increased their food intake, despite having no change in body mass. Circadian wheel-running activity was also altered in phase-advanced mice. These results provide further evidence that chronobiological disruptions can lead to alterations in physiology and behavior, and that exercise can alleviate some of those symptoms.

Mismatch study of C-ADS main linac**Supported by China ADS Project (XDA03020000) and National Natural Science Foundation of China (11235012)

The ADS accelerator in China is a Continuous-Wave (CW) proton linac with 1.5 GeV beam energy, 10 mA beam current, and 15 MW beam power. To meet the extremely low beam loss rate and high reliability requirements, it is very important to study the beam halo caused by beam mismatch, which is one major sources of beam loss. To avoid envelope instability, the phase advances per period are all smaller than 90 degrees in the main linac design. In this paper, simulation results of the emittance growth and the envelope oscillations caused by mismatch in the main linac section are presented. To meet the emittance growth requirement, the transverse and longitudinal mismatch factors should be smaller than 0.4 and 0.3, respectively.

S.16.02 Chronotherapeutics to target the biological clock, heal depression and prevent suicide

Given the strong relationship between circadian rhythm disruption and mood regulation, combined chronotherapeutic approaches have been proposed for mood disorders. However, a comprehensive review of the available evidence on the efficacy of such interventions for depression is lacking.To systematically review available literature on Triple Chronotherapy (Sleep Deprivation – Sleep Phase Advance – Bright Light Therapy) for depressive symptoms in Major Depression and Bipolar Depression.We followed the PRISMA statement for systematic reviews to conduct a web-based search on PubMed, Scopus and Embase using a list of selected keywords relevant to depression and chronotherapy.After title and abstract screening of the 321 records retrieved, 25 potentially eligible studies were assessed at full-text screening. Nineteen studies were excluded for failure to match inclusion criteria. Six records of Triple Chronotherapy in addition to conventional treatment, published between 2009 and 2019, were included in the revision. All studies reported significant improvements on HAM–D scores at the end of treatment, with 50% to 84% response rates. Efficacy of treatment was confirmed on follow-up by three studies, with 58% to 61% response rates. Remission rates varied from 33,3% to 77%. Reported side effects were negligible across studies.Available trials are very few and only one included a control group treated with a daily exercise program.The limited literature suggests that Triple chronotherapy might be a safe and effective addition to conventional antidepressant interventions, although well–designed, randomized controlled trials are needed.

Triptans attenuate circadian responses to light.

Daily exposure to light synchronizes the circadian clock, located in the suprachiasmatic nucleus (SCN), to external day/night cycles. These responses to light can be modified by serotonergic drugs, such as serotonin 5HT1B receptor agonists. Triptans are specific 5HT1B agonists prescribed to treat migraines. Here, we examined the effects of two triptans (zolmitriptan and sumatriptan) on photic phase resetting in Syrian hamsters. Pre-treatment with intra-SCN sumatriptan significantly attenuates, and at higher doses completely blocks, phase advances to light during the late night. Pre-treatment with systemic zolmitriptan significantly attenuates both light-induced phase advances and phase delays. Neither of these drugs, nor their vehicles, causes phase shifts on their own. Pre-treatment with zolmitriptan also significantly reduces the expression of light-induced c-fos in the SCN. Neither zolmitriptan nor vehicle alone induces significant c-fos expression in the SCN. Finally, pre-treatment with zolmitriptan does not attenuate phase shifts to intra-SCN N-methyl-d-aspartate injections, indicating that the mechanism of action for zolmitriptan is likely to be through activation of presynaptic 5HT1B receptors on retinal terminals, thereby decreasing light-induced neurotransmitter release. As triptans are commercially available medications, there is potential for their use in blocking unwanted photic phase shifting during shift-work or jet-lag. Additionally, triptans may also affect the circadian clock in patients receiving them regularly for migraines. Finally, our results may hint at the mechanism by which triptans can alleviate the photophobia that frequently accompanies migraines, namely by activating 5HT1B receptors on retinal terminals elsewhere in the brain, and thereby diminishing visually-evoked neurotransmitter signalling in those areas.

Temporal changes of light-induced proteins in the SCN following treatment with the serotonin mixed agonist/antagonist BMY7378.

The 5-HT1A mixed agonist/antagonist BMY7378 has been shown to greatly potentiate photic phase advances in hamsters. The underlying mechanism and intracellular changes in the suprachiasmatic nucleus (SCN) by which this potentiation is accomplished have yet to be fully determined. Here, we examine the effect of BMY7378 on temporal activation patterns of a number of proteins and enzymes in the SCN following light exposure in the late subjective night. BMY7378 administration increased the amount of several photo-inducible proteins in the SCN at specific time points following light exposure in the late subjective night. Relative to animals given saline before a light pulse, the number of cells immunoreactive for cFos, JunB and PER1 was all significantly greater 360 min following the light pulse in BMY7378 pretreated animals, indicating an extended action of these light-induced proteins in the SCN following BMY7378 pretreatment. Aside from a modest, nonsignificant increase in P-ERK levels at 60 min, BMY7378 did not affect light-induced P-ERK levels. The levels of light-induced P-CREB were similarly unaffected by BMY7378. Also unaffected by BMY7378 treatment were cFos expression and JunB expression at 120 and 180 min following light exposure. These findings suggest that BMY7378 may potentiate photic phase shifts at least partly by prolonging the activity of some, but not all, light-induced proteins and biochemical pathways involved in coupling the light signal to the output of the circadian clock, particularly those which are active many hours after the light signal reaches the SCN.

Photoperiod sensitivity of the Arabidopsis circadian clock is tissue-specific

Tissue-specific functions of the circadian clock in Arabidopsis have recently been revealed. The vasculature clock shows distinctive gene expression profiles compared to the clock in other tissues under light-dark cycles. However, it has not yet been established whether the vasculature clock also shows unique gene expression patterns that correlate with temperature cycles, another important environmental cue. Here, we detected diel phase of TIMING OF CAB EXPRESSION 1 (TOC1) expression in the vasculature and whole leaf under long-day light-dark cycles and temperature cycles. We found that the vasculature clock had advanced TOC1 phase under light-dark cycles but not under temperature cycles, suggesting that the vasculature clock has lower sensitivity against temperature signals. Furthermore, the phase advancement of TOC1 was seen only under long-day condition but not under short-day condition. These results support our previous conclusion that the circadian clock in vasculature preferentially senses photoperiodic signals.

Predicted Role of NAD Utilization in the Control of Circadian Rhythms during DNA Damage Response.

The circadian clock is a set of regulatory steps that oscillate with a period of approximately 24 hours influencing many biological processes. These oscillations are robust to external stresses, and in the case of genotoxic stress (i.e. DNA damage), the circadian clock responds through phase shifting with primarily phase advancements. The effect of DNA damage on the circadian clock and the mechanism through which this effect operates remains to be thoroughly investigated. Here we build an in silico model to examine damage-induced circadian phase shifts by investigating a possible mechanism linking circadian rhythms to metabolism. The proposed model involves two DNA damage response proteins, SIRT1 and PARP1, that are each consumers of nicotinamide adenine dinucleotide (NAD), a metabolite involved in oxidation-reduction reactions and in ATP synthesis. This model builds on two key findings: 1) that SIRT1 (a protein deacetylase) is involved in both the positive (i.e. transcriptional activation) and negative (i.e. transcriptional repression) arms of the circadian regulation and 2) that PARP1 is a major consumer of NAD during the DNA damage response. In our simulations, we observe that increased PARP1 activity may be able to trigger SIRT1-induced circadian phase advancements by decreasing SIRT1 activity through competition for NAD supplies. We show how this competitive inhibition may operate through protein acetylation in conjunction with phosphorylation, consistent with reported observations. These findings suggest a possible mechanism through which multiple perturbations, each dominant during different points of the circadian cycle, may result in the phase advancement of the circadian clock seen during DNA damage.

Effect of arousing stimuli on circulating corticosterone and the circadian rhythms of luteinizing hormone (LH) surges and locomotor activity in estradiol-treated ovariectomized (ovx + EB) Syrian hamsters

In most proestrous hamsters, novel wheel exposure phase advances activity rhythms and blocks the preovulatory LH surge, which occurs 2h earlier the next day. Because wheel immobilization does not prevent these effects we hypothesized that arousal alone blocks and phase advances the LH surge. Ovariectomized (ovx) hamsters received a jugular vein cannula and estradiol benzoate (EB) or vehicle was injected sc. The next day (Day 1), at zeitgeber time (ZT) 4–5 (ZT 12=lights off), after obtaining a blood sample, each hamster was exposed to constant darkness (DD), and either remained in her home cage or was transferred to a new cage and exposed to a running wheel or a 2-hour arousal paradigm. Blood samples were obtained in dim red light and activity was recorded hourly until ~ZT 10–11 on Days 1 and 2. For the next 1–2weeks, activity was monitored in DD. Plasma LH and corticosterone were assessed by RIA. Novel wheel exposure or arousal at ZT 4 greatly attenuated the Day 1 LH surge in ovx+EB hamsters, and phase advanced the Day 2 LH surge by about 2h. In proestrous hamsters, novel wheel exposure led to a prolonged (>2h) increase in corticosterone levels only when LH surges were blocked. Phase advances in activity rhythms were enhanced by estradiol and arousal. The results suggest that estradiol modulates the effectiveness of non-photic stimuli. The role of the increased activity of the hypothalamic–pituitary–adrenal axis associated with novel wheel-induced attenuation of LH surges in ovx+EB hamsters remains to be determined.

Altered circadian rhythm and metabolic gene profile in rats subjected to advanced light phase shifts.

The circadian clock regulates metabolic homeostasis and its disruption predisposes to obesity and other metabolic diseases. However, the effect of phase shifts on metabolism is not completely understood. We examined whether alterations in the circadian rhythm caused by phase shifts induce metabolic changes in crucial genes that would predispose to obesity. Three-month-old rats were maintained on a standard diet under lighting conditions with chronic phase shifts consisting of advances, delays or advances plus delays. Serum leptin, insulin and glucose levels decreased only in rats subjected to advances. The expression of the clock gene Bmal 1 increased in the hypothalamus, white adipose tissue (WAT), brown adipose tissue (BAT) and liver of the advanced group compared to control rats. The advanced group showed an increase in hypothalamic AgRP and NPY mRNA, and their lipid metabolism gene profile was altered in liver, WAT and BAT. WAT showed an increase in inflammation and ER stress and brown adipocytes suffered a brown-to-white transformation and decreased UCP-1 expression. Our results indicate that chronic phase advances lead to significant changes in neuropeptides, lipid metabolism, inflammation and ER stress gene profile in metabolically relevant tissues such as the hypothalamus, liver, WAT and BAT. This highlights a link between alteration of the circadian rhythm and metabolism at the transcriptional level.

Synchronization properties of heterogeneous neuronal networks with mixed excitability type.

We study the synchronization of neuronal networks with dynamical heterogeneity, showing that network structures with the same propensity for synchronization (as quantified by master stability function analysis) may develop dramatically different synchronization properties when heterogeneity is introduced with respect to neuronal excitability type. Specifically, we investigate networks composed of neurons with different types of phase response curves (PRCs), which characterize how oscillating neurons respond to excitatory perturbations. Neurons exhibiting type 1 PRC respond exclusively with phase advances, while neurons exhibiting type 2 PRC respond with either phase delays or phase advances, depending on when the perturbation occurs. We find that Watts-Strogatz small world networks transition to synchronization gradually as the proportion of type 2 neurons increases, whereas scale-free networks may transition gradually or rapidly, depending upon local correlations between node degree and excitability type. Random placement of type 2 neurons results in gradual transition to synchronization, whereas placement of type 2 neurons as hubs leads to a much more rapid transition, showing that type 2 hub cells easily "hijack" neuronal networks to synchronization. These results underscore the fact that the degree of synchronization observed in neuronal networks is determined by a complex interplay between network structure and the dynamical properties of individual neurons, indicating that efforts to recover structural connectivity from dynamical correlations must in general take both factors into account.

Chronic shifts in the length and phase of the light cycle increase intermittent alcohol drinking in C57BL/6J mice.

Introduction: Shift workers—e.g., health care professionals, truck drivers, and factory workers—are forced to maintain daily cycles at odds with their natural circadian rhythms and as a consequence need to frequently readjust these cycles. This shift work-induced circadian desynchrony (CD) is associated with increased sleep disorders and with alcohol abuse. Nonetheless, it has proven difficult to model CD-induced changes in alcohol consumption in mouse models, which is an important step toward identifying the mechanisms by which CD increases alcohol intake. This study examined whether frequent changes in the light cycle could increase free access alcohol intake in a mouse line that readily consumes alcohol.Methods: Free access alcohol intake, water intake, and wheel-running activity patterns of male C57BL/6J mice were measured while the mice were maintained on a normal 12HR photoperiod for baseline data for 2 weeks. The mice were then exposed to an alternating photoperiod of 12 h and 18 h, with light onset advanced 8 h during the 18HR photoperiod. The photoperiods rotated every 3 days, for 21 days total.Results: The repeated pattern of phase advances and delays, with a concurrent change in the length of the photoperiod, shifted mice to a pattern of intermittent alcohol drinking without altering water intake. Wheel running activity demonstrated that mice were unable to reset their behavioral clocks during CD, showing constant, low-level activity with no peak in activity at the start of the dark phase and greater activity during the morning light phase.Conclusion: It is possible to model CD effects on alcohol intake in C57BL/6J mice using a pattern of phase shifts and changes in the photoperiod. Using this model, we demonstrate that mice begin intermittent drinking during CD, and this increase in alcohol intake does not correlate with an increase in overall activity or in overall fluid intake.

Effect of entrapped phase on the filling characteristics of closed-end nanopores.

We investigated the filling dynamics in closed-end capillaries of sub-micron length scale, in which the displacing phase advances at the expense of the entrapped phase. Contrary to common intuition, we reveal that the existence of a displaced phase in a closed-end nano-scale system does not necessarily retard the meniscus advancement over all temporal regimes, unlike what is observed in cases of macro-scale capillaries, but can also sometimes augment the local filling rates. We determined that the combined effect of surface wettability and the displaced phase molecules resulted from the pinning-depinning of the meniscus, and hence, from the local dynamics of capillary filling. We also employed a simple force balance-based model to capture the essential interfacial phenomena governing this behavior, and benchmarked the same with our molecular dynamics simulations. Our results suggest a possible mechanism for modifying the effective wettabilities of nano-scale capillaries without any modification of the surface architecture or chemical treatment of the surface.

Different effects of phase advance and delay in rotating light-dark regimens on clock and natriuretic peptide gene expression in the rat heart.

Under physiological conditions the mammalian circadian system is synchronized to a cyclic environment. The central oscillator in the suprachiasmatic nuclei (SCN) responds predominantly to an external light (L) dark (D) cycle. Peripheral oscillators are more efficiently synchronized by metabolic cues. When the circadian system is exposed to opposing synchronizing cues, peripheral oscillators uncouple from the SCN. To consider influence of phase advances and delays in light regimens mimicking shift work, we analyzed the expression of clock genes (per2, bmal1) and natriuretic peptides (anp, bnp) in the heart of male rats. Experimental groups were exposed to a rotating LD regimen with either 8 h phase advance or delay for 11 weeks. Samples were taken for a 24 h cycle in 4 h intervals. Peripheral oscillators responded to rotating phase advance by decreasing rhythm robustness, while phase delay mostly influenced the phase angle between the acrophase of rhythmic gene expression and the external LD cycle. The expression of anp was arrhythmic in the heart of control rats and was not influenced by rotating LD regimens. The expression of bnp showed a daily rhythm with a nadir during the active phase. The daily rhythm in bnp expression diminished under rotating LD regimen conditions.

English

2 ABSTRACT: Brushless Direct Current (BLDC) motors are widely used due to high reliability, simple frame, straight forward control, and low friction. BLDC motor has the advantage of high speed adjusting performance and high power density. Speaking of the motor drive control, the most important part is commutation control. On the other hand, they show a high torque ripple characteristics caused by nonideal commutation currents. This limits its application area especially for the low-voltage applications. In order to minimize torque ripple for the entire speed range, a ample analysis of commutation torque ripple was made according to phase advancing (PA) commutation control method. This approach is based on the terminal voltage sensing and converting the voltages into d-q reference frame and the commutation signals are generated by comparing it with reference values. The gating signals are obtained by switching sequence of BLDC motor and it is done using fuzzy logic controller(FLC).The design analysis and simulation of the proposed system is done using MATLAB version 2013a and the simulation results of proportional-integral (PI) controller and fuzzy logic controller(FLC) method is compared.