JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Stress-Induced Changes in the Expression of the Clock Protein PERIOD1 in the Rat Limbic Forebrain and Hypothalamus: Role of Stress Type, Time of Day, and Predictability.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Stressful events can disrupt circadian rhythms in mammals but mechanisms underlying this disruption remain largely unknown. One hypothesis is that stress alters circadian protein expression in the forebrain, leading to functional dysregulation of the brain circadian network and consequent disruption of circadian physiological and behavioral rhythms. Here we characterized the effects of several different stressors on the expression of the core clock protein, PER1 and the activity marker, FOS in select forebrain and hypothalamic nuclei in rats. We found that acute exposure to processive stressors, restraint and forced swim, elevated PER1 and FOS expression in the paraventricular and dorsomedial hypothalamic nuclei and piriform cortex but suppressed PER1 and FOS levels exclusively in the central nucleus of the amygdala (CEAl) and oval nucleus of the bed nucleus of the stria terminalis (BNSTov). Conversely, systemic stressors, interleukin-1? and 2-Deoxy-D-glucose, increased PER1 and FOS levels in all regions studied, including the CEAl and BNSTov. PER1 levels in the suprachiasmatic nucleus (SCN), the master pacemaker, were unaffected by any of the stress manipulations. The effect of stress on PER1 and FOS was modulated by time of day and, in the case of daily restraint, by predictability. These results demonstrate that the expression of PER1 in the forebrain is modulated by stress, consistent with the hypothesis that PER1 serves as a link between stress and the brain circadian network. Furthermore, the results show that the mechanisms that control PER1 and FOS expression in CEAl and BNSTov are uniquely sensitive to differences in the type of stressor. Finally, the finding that the effect of stress on PER1 parallels its effect on FOS supports the idea that Per1 functions as an immediate-early gene. Our observations point to a novel role for PER1 as a key player in the interface between stress and circadian rhythms.
Related JoVE Video
Diurnal influences on electrophysiological oscillations and coupling in the dorsal striatum and cerebellar cortex of the anesthetized rat.
Front Syst Neurosci
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Circadian rhythms modulate behavioral processes over a 24 h period through clock gene expression. What is largely unknown is how these molecular influences shape neural activity in different brain areas. The clock gene Per2 is rhythmically expressed in the striatum and the cerebellum and its expression is linked with daily fluctuations in extracellular dopamine levels and D2 receptor activity. Electrophysiologically, dopamine depletion enhances striatal local field potential (LFP) oscillations. We investigated if LFP oscillations and synchrony were influenced by time of day, potentially via dopamine mechanisms. To assess the presence of a diurnal effect, oscillatory power and coherence were examined in the striatum and cerebellum of rats under urethane anesthesia at four different times of day zeitgeber time (ZT1, 7, 13 and 19-indicating number of hours after lights turned on in a 12:12 h light-dark cycle). We also investigated the diurnal response to systemic raclopride, a D2 receptor antagonist. Time of day affected the proportion of LFP oscillations within the 0-3 Hz band and the 3-8 Hz band. In both the striatum and the cerebellum, slow oscillations were strongest at ZT1 and weakest at ZT13. A 3-8 Hz oscillation was present when the slow oscillation was lowest, with peak 3-8 Hz activity occurring at ZT13. Raclopride enhanced the slow oscillations, and had the greatest effect at ZT13. Within the striatum and with the cerebellum, 0-3 Hz coherence was greatest at ZT1, when the slow oscillations were strongest. Coherence was also affected the most by raclopride at ZT13. Our results suggest that neural oscillations in the cerebellum and striatum, and the synchrony between these areas, are modulated by time of day, and that these changes are influenced by dopamine manipulation. This may provide insight into how circadian gene transcription patterns influence network electrophysiology. Future experiments will address how these network alterations are linked with behavior.
Related JoVE Video
Phase differences in expression of circadian clock genes in the central nucleus of the amygdala, dentate gyrus, and suprachiasmatic nucleus in the rat.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
We performed a high temporal resolution analysis of the transcript level of two core clock genes, Period2 (Per2) and Bmal1, and a clock output gene, Dbp, in the suprachiasmatic nucleus (SCN), the master circadian clock, and in two forebrain regions, the lateral part of the central nucleus of the amygdala (CEAl), and dentate gyrus (DG), in rats. These regions, as we have shown previously, exhibit opposite rhythms in expression of the core clock protein, PERIOD2 (PER2). We found that the expression of Per2, Bmal1 and Dbp follow a diurnal rhythm in all three regions but the phase and amplitude of the rhythms of each gene vary across regions, revealing important regional differences in temporal dynamics underlying local daily rhythm generation in the mammalian forebrain. These findings underscore the complex temporal organization of subordinate circadian oscillators in the forebrain and raise interesting questions about the functional connection of these oscillators with the master SCN clock.
Related JoVE Video
Translational control of entrainment and synchrony of the suprachiasmatic circadian clock by mTOR/4E-BP1 signaling.
Neuron
PUBLISHED: 06-17-2013
Show Abstract
Hide Abstract
Protein synthesis is critical for circadian clock function, but little is known of how translational regulation controls the master pacemaker in mammals, the suprachiasmatic nucleus (SCN). Here we demonstrate that the pivotal translational repressor, the eukaryotic translational initiation factor 4E binding protein 1 (4E-BP1), is rhythmically regulated via the mechanistic target of rapamycin (mTOR) signaling in the SCN and preferentially represses vasoactive intestinal peptide (Vip) mRNA translation. Knockout (KO) of Eif4ebp1 (gene encoding 4E-BP1) leads to upregulation of VIP and higher amplitude of molecular rhythms in the SCN. Consequently, the 4E-BP1 null mice exhibit accelerated re-entrainment to a shifted light/dark cycle and are more resistant to the rhythm-disruptive effects of constant light. Conversely, in Mtor(+/-) mice VIP expression is decreased and susceptibility to the effects of constant light is increased. These results reveal a key role for mTOR/4E-BP1-mediated translational control in regulating entrainment and synchrony of the master clock.
Related JoVE Video
Membrane assembly during the infection cycle of the giant Mimivirus.
PLoS Pathog.
PUBLISHED: 05-01-2013
Show Abstract
Hide Abstract
Although extensively studied, the structure, cellular origin and assembly mechanism of internal membranes during viral infection remain unclear. By combining diverse imaging techniques, including the novel Scanning-Transmission Electron Microscopy tomography, we elucidate the structural stages of membrane biogenesis during the assembly of the giant DNA virus Mimivirus. We show that this elaborate multistage process occurs at a well-defined zone localized at the periphery of large viral factories that are generated in the host cytoplasm. Membrane biogenesis is initiated by fusion of multiple vesicles, ~70 nm in diameter, that apparently derive from the host ER network and enable continuous supply of lipid components to the membrane-assembly zone. The resulting multivesicular bodies subsequently rupture to form large open single-layered membrane sheets from which viral membranes are generated. Membrane generation is accompanied by the assembly of icosahedral viral capsids in a process involving the hypothetical major capsid protein L425 that acts as a scaffolding protein. The assembly model proposed here reveals how multiple Mimivirus progeny can be continuously and efficiently generated and underscores the similarity between the infection cycles of Mimivirus and Vaccinia virus. Moreover, the membrane biogenesis process indicated by our findings provides new insights into the pathways that might mediate assembly of internal viral membranes in general.
Related JoVE Video
Peripheral circadian clocks--a conserved phenotype?
Chronobiol. Int.
PUBLISHED: 02-20-2013
Show Abstract
Hide Abstract
The circadian system of mammals regulates the timing of occurrence of behavioral and physiological events, thereby optimizing adaptation to their surroundings. This system is composed of a single master pacemaker located in the suprachiasmatic nucleus (SCN) and a population of peripheral clocks. The SCN integrates time information from exogenous sources and, in turn, synchronizes the downstream peripheral clocks. It is assumed that under normal conditions, the circadian phenotype of different peripheral clocks would be conserved with respect to its period and robustness. To study this idea, we measured the daily wheel-running activity (WRA; a marker of the SCN output) in 84 male inbred LEW/Crl rats housed under a 12 h:12 h light-dark cycle. In addition, we assessed the mRNA expression of two clock genes, rPer2 and rBmal1, and one clock-controlled gene, rDbp, in four tissues that have the access to time cues other than those emanating from the SCN: olfactory bulbs (OBs), liver, tail skin, and white blood cells (WBCs). In contrast with the assumption stated above, we found that circadian clocks in peripheral tissues differ in the temporal pattern of the expression of circadian clock genes, in the robustness of the rhythms, and possibly in the number of functional ~24-h-clock cells. Based on the tissue diversity in the robustness of the clock output, the hepatic clock is likely to house the highest number of functional ~24-h-clock cells, and the OBs, the fewest number. Thus, the phenotype of the circadian clock in the periphery is tissue specific and may depend not only on the SCN but also on the sensitivity of the tissue to non-SCN-derived time cues. In the OBs and liver, the circadian clock phenotypes seem to be dominantly shaped by the SCN output. However, in the tail skin and WBC, other time cues participate in the phenotype design. Finally, our study suggests that the basic phenotype of the circadian clock is constructed at the transcript level of the core clock genes. Yet, additional posttranscriptional and translational events can contribute to the robustness and periodicity of the clock output.
Related JoVE Video
Recording and analysis of circadian rhythms in running-wheel activity in rodents.
J Vis Exp
PUBLISHED: 02-06-2013
Show Abstract
Hide Abstract
When rodents have free access to a running wheel in their home cage, voluntary use of this wheel will depend on the time of day. Nocturnal rodents, including rats, hamsters, and mice, are active during the night and relatively inactive during the day. Many other behavioral and physiological measures also exhibit daily rhythms, but in rodents, running-wheel activity serves as a particularly reliable and convenient measure of the output of the master circadian clock, the suprachiasmatic nucleus (SCN) of the hypothalamus. In general, through a process called entrainment, the daily pattern of running-wheel activity will naturally align with the environmental light-dark cycle (LD cycle; e.g. 12 hr-light:12 hr-dark). However circadian rhythms are endogenously generated patterns in behavior that exhibit a ~24 hr period, and persist in constant darkness. Thus, in the absence of an LD cycle, the recording and analysis of running-wheel activity can be used to determine the subjective time-of-day. Because these rhythms are directed by the circadian clock the subjective time-of-day is referred to as the circadian time (CT). In contrast, when an LD cycle is present, the time-of-day that is determined by the environmental LD cycle is called the zeitgeber time (ZT). Although circadian rhythms in running-wheel activity are typically linked to the SCN clock, circadian oscillators in many other regions of the brain and body could also be involved in the regulation of daily activity rhythms. For instance, daily rhythms in food-anticipatory activity do not require the SCN and instead, are correlated with changes in the activity of extra-SCN oscillators. Thus, running-wheel activity recordings can provide important behavioral information not only about the output of the master SCN clock, but also on the activity of extra-SCN oscillators. Below we describe the equipment and methods used to record, analyze and display circadian locomotor activity rhythms in laboratory rodents.
Related JoVE Video
Comprehensive mapping of regional expression of the clock protein PERIOD2 in rat forebrain across the 24-h day.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
In mammals, a light-entrainable clock located in the suprachiasmatic nucleus (SCN) regulates circadian rhythms by synchronizing oscillators throughout the brain and body. Notably, the nature of the relation between the SCN clock and subordinate oscillators in the rest of the brain is not well defined. We performed a high temporal resolution analysis of the expression of the circadian clock protein PERIOD2 (PER2) in the rat forebrain to characterize the distribution, amplitude and phase of PER2 rhythms across different regions. Eighty-four LEW/Crl male rats were entrained to a 12-h: 12-h light/dark cycle, and subsequently perfused every 30 min across the 24-h day for a total of 48 time-points. PER2 expression was assessed with immunohistochemistry and analyzed using automated cell counts. We report the presence of PER2 expression in 20 forebrain areas important for a wide range of motivated and appetitive behaviors including the SCN, bed nucleus, and several regions of the amygdala, hippocampus, striatum, and cortex. Eighteen areas displayed significant PER2 rhythms, which peaked at different times of day. Our data demonstrate a previously uncharacterized regional distribution of rhythms of a clock protein expression in the brain that provides a sound basis for future studies of circadian clock function in animal models of disease.
Related JoVE Video
Variable restricted feeding disrupts the daily oscillations of Period2 expression in the limbic forebrain and dorsal striatum in rats.
J. Mol. Neurosci.
PUBLISHED: 03-03-2011
Show Abstract
Hide Abstract
Predictable restricted feeding schedules limit food availability to a single meal at the same time each day, lead to the induction and entrainment of circadian rhythms in food-anticipatory activity, and shift daily rhythms of clock gene expression in areas of the brain that are important in the regulation of motivational and emotional state. In contrast, when food is delivered under a variable restricted feeding (VRF) schedule, at a new and unpredictable mealtime each day, circadian rhythms in food-anticipatory activity fail to develop. Here, we study the effects of VRF on the daily rhythm of plasma corticosterone and of clock gene expression in the limbic forebrain and dorsal striatum, of rats provided a 2-h access to a complete meal replacement (Ensure Plus) at an unpredictable time each day. VRF schedules varied the mealtimes within the 12 h of light (daytime VRF), the 12 h of dark (nighttime VRF), or across the 24 h light-dark cycle (anytime VRF). Our results show that contrary to the synchronizing effects of predictable restricted feeding, VRF blunts the daily corticosterone rhythm and disrupts daily rhythms of PER2 expression in a region-specific and mealtime-dependent manner.
Related JoVE Video
Global depletion of dopamine using intracerebroventricular 6-hydroxydopamine injection disrupts normal circadian wheel-running patterns and PERIOD2 expression in the rat forebrain.
J. Mol. Neurosci.
PUBLISHED: 02-02-2011
Show Abstract
Hide Abstract
Normal circadian rhythms of behavior are disrupted in disorders involving the dopamine (DA) system, such as Parkinsons disease. We have reported previously using unilateral injections of the catecholamine toxin, 6-hydroxydopamine (6-OHDA), into the medial forebrain bundle that DA signaling regulates daily expression of the clock protein, PERIOD2 (PER2), in the dorsal striatum of the rat. In the present study, we made widespread lesions of DA fibers using large injections of 6-OHDA into the third ventricle to determine the involvement of DA in normal daily rhythms of wheel-running activity and PER2 patterns in the suprachiasmatic nucleus (SCN) and several regions of the limbic forebrain. Rats injected with 6-OHDA and housed in constant darkness were less active in the wheel and showed a disorganized pattern of activity in which wheel running was not confined to a specific phase over 24 h. The 6-OHDA injection had no effect on the daily PER2 pattern in the SCN, but blunted the normal rise in PER2 in the dorsal striatum. 6-OHDA also blunted PER2 expression in the periventricular nucleus of the hypothalamus, a region in which a daily PER2 pattern has not been previously reported in male rats, and in the oval nucleus of the bed nucleus of the stria terminalis, but not in the central nucleus of the amygdala. These results indicate that DA plays a prominent role in regulating circadian activity at both behavioral and molecular levels.
Related JoVE Video
Endogenous dopamine regulates the rhythm of expression of the clock protein PER2 in the rat dorsal striatum via daily activation of D2 dopamine receptors.
J. Neurosci.
PUBLISHED: 10-22-2010
Show Abstract
Hide Abstract
A role for dopamine (DA) in the regulation of clock genes in the mammalian brain is suggested by evidence that manipulations of DA receptors can alter the expression of some clock genes outside the suprachiasmatic nucleus (SCN), the master circadian clock. The role of endogenous DA in the regulation of clock gene expression is unknown. Here, we demonstrate a direct relationship between extracellular DA levels and the rhythm of expression of the clock protein PERIOD2 (PER2) in the dorsal striatum of the male Wistar rat. Specifically, we show that the peak of the daily rhythm of extracellular DA in the dorsal striatum precedes the peak of PER2 by ?6 h and that depletion of striatal DA by 6-hydroxydopamine or ?-methyl-para-tyrosine or blockade of D(2) DA receptors by raclopride blunts the rhythm of striatal PER2. Furthermore, timed daily activation of D(2) DA receptors, but not D(1) DA receptors, restores and entrains the PER2 rhythm in the DA-depleted striatum. None of these manipulations had any effect on the PER2 rhythm in the SCN. Our findings are consistent with the idea that the rhythm of expression of PER2 in the dorsal striatum depends on daily dopaminergic activation of D(2) DA receptors. These observations may have implications for circadian abnormalities seen in Parkinsons disease.
Related JoVE Video
Variations in daily expression of the circadian clock protein, PER2, in the rat limbic forebrain during stable entrainment to a long light cycle.
J. Mol. Neurosci.
PUBLISHED: 09-02-2010
Show Abstract
Hide Abstract
The circadian clock in the mammalian suprachiasmatic nucleus (SCN) can be entrained by light cycles longer than the normal 24-h light/dark (LD) cycle, but little is known about the effect of such cycles on circadian clocks outside the SCN. Here we examined the effect of exposure to a 26-h T cycle (T26, 1 h:25 h LD) on patterns of expression of the clock protein, PERIOD2 (PER2), in the SCN and in four regions of the limbic forebrain known to exhibit robust circadian oscillations in PER2: the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), central nucleus of the amygdala (CEA), basolateral amygdala (BLA), and dentate gyrus (DG). All rats showed stable entrainment of running wheel activity rhythms to the T26 cycle. As previously shown, PER2 expression in the SCN was stably entrained, peaking around the onset of locomotor activity. In contrast, exposure to the T26 cycle uncoupled the rhythms of PER2 expression in the BNSTov and CEA from that of the SCN, whereas PER2 rhythms in the BLA and DG were unaffected. These results show that exposure to long light cycles can uncouple circadian oscillators in select nuclei of the limbic forebrain from the SCN clock and suggest that such cycles may be used to study the functional consequences of coupling and uncoupling of brain circadian oscillators.
Related JoVE Video
Exogenous corticosterone induces the expression of the clock protein, PERIOD2, in the oval nucleus of the bed nucleus of the stria terminalis and the central nucleus of the amygdala of adrenalectomized and intact rats.
J. Mol. Neurosci.
PUBLISHED: 03-30-2010
Show Abstract
Hide Abstract
The cyclical expression of the clock protein PERIOD2 (PER2) in select regions of the limbic forebrain is contingent upon the rhythmic secretion of the adrenal glucocorticoid, corticosterone. Daily rhythmic PER2 expression in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) and the central nucleus of the amygdala (CEA) is abolished with the removal of the adrenal glands but restored with rhythmic hormone replacement via the drinking water at a time corresponding to the endogenous peak of circulating glucocorticoids. Here, we investigated the effects of serial or acute systemic injections of corticosterone on the expression of PER2 in the BNSTov and CEA of both adrenalectomized (ADX) and intact rats. We sought to determine whether there is a temporal window of corticosterone sensitivity by delivering the hormone at a time corresponding to trough levels of circulating glucocorticoids, at lights on. We found that daily morning injections of corticosterone induced PER2 expression in the BNSTov and CEA of ADX rats, with levels peaking 1 h after injection. In intact rats, daily morning injections significantly upregulated the expression of PER2 in the BNSTov and CEA 1 h after injection and dampened the evening peak, while a single injection abolished the rhythm of PER2 expression in the CEA but had no effect on PER2 in the BNSTov. Our findings suggest that despite the potential masking effect of signals from the light-entrained master clock, daytime chronic and acute corticosterone administration can alter the rhythmic expression of PER2 in the BNSTov and CEA, and that the response is region-specific and dependent on the duration of treatment.
Related JoVE Video
Glucocorticoid regulation of clock gene expression in the mammalian limbic forebrain.
J. Mol. Neurosci.
PUBLISHED: 01-04-2010
Show Abstract
Hide Abstract
Glucocorticoids regulate a wide variety of functions, including synaptic plasticity, hypothalamic-pituitary-adrenal axis activation, conditional fear learning, metabolism, and sensitization to drugs of abuse. The diurnal secretion of glucocorticoids, driven by the mammalian master clock located in the suprachiasmatic nucleus of the hypothalamus, has been shown to induce and entrain clock gene expression in peripheral tissues. However, little attention has been given to the form and function of centrally located subordinate oscillators, and the synchronizing factors that influence them. Here we review findings that implicate glucocorticoids in the circadian regulation of clock genes in select oscillators in the limbic forebrain and propose mechanisms whereby glucocorticoids can feed back on rhythms downstream from the master clock and possibly alter the functional output of these nuclei.
Related JoVE Video
Circadian rhythms of PERIOD1 expression in the dorsomedial hypothalamic nucleus in the absence of entrained food-anticipatory activity rhythms in rats.
Eur. J. Neurosci.
PUBLISHED: 05-21-2009
Show Abstract
Hide Abstract
When food availability is restricted to a single time of day, circadian rhythms of behavior and physiology in rodents shift to anticipate the predictable time of food arrival. It has been hypothesized that certain food-anticipatory rhythms are linked to the induction and entrainment of rhythms in clock gene expression in the dorsomedial hypothalamic nucleus (DMH), a putative food-entrained circadian oscillator. To study this concept further, we made food availability unpredictable by presenting the meal at a random time each day (variable restricted feeding, VRF), either during the day, night or throughout the 24-h cycle. Wheel running activity and the expression of the clock protein, Period1 (PER1), in the DMH and the suprachiasmatic nucleus (SCN) were assessed. Rats exhibited increased levels of activity during the portion of the day when food was randomly presented but, as expected, failed to entrain anticipatory wheel running activity to a single time of day. PER1 expression in the SCN was unchanged by VRF schedules. In the DMH, PER1 expression became rhythmic, peaking at opposite times of day in rats fed only during the day or during the night. In rats fed randomly throughout the entire 24-h cycle, PER1 expression in the DMH remained arrhythmic, but was elevated. These results demonstrate that VRF schedules confined to the day or night can induce circadian rhythms of clock gene expression in the DMH. Such feeding schedules cannot entrain behavioral rhythms, thereby showing that food-entrainment of behavior and circadian rhythms of clock gene expression in the DMH are dissociable.
Related JoVE Video
Motivational Modulation of Rhythms of the Expression of the Clock Protein PER2 in the Limbic Forebrain.
Biol. Psychiatry
PUBLISHED: 02-06-2009
Show Abstract
Hide Abstract
Key molecular components of the mammalian circadian clock are expressed rhythmically in many brain areas and peripheral tissues in mammals. Here we review findings from our work on rhythms of expression of the clock protein Period2 (PER2) in four regions of the limbic forebrain known to be important in the regulation of motivational and emotional states. These regions include the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), the central nucleus of the amygdala (CEA), the basolateral amygdala (BLA), and the dentate gyrus (DG). Daily rhythms in the expression of PER2 in these regions are controlled by the master circadian pacemaker, the suprachiasmatic nucleus (SCN), but, importantly, they are also sensitive to homeostatic perturbations and to hormonal states that directly influence motivated behavior. Thus, circadian information from the SCN and homeostatic signals are integrated in these regions of the limbic forebrain to affect the temporal organization of motivational and emotional processes.
Related JoVE Video
Behavioral and hormonal regulation of expression of the clock protein, PER2, in the central extended amygdala.
Prog. Neuropsychopharmacol. Biol. Psychiatry
PUBLISHED: 01-20-2009
Show Abstract
Hide Abstract
PER2, a key molecular component of the mammalian circadian clock, is expressed rhythmically in many brain areas and peripheral tissues in mammals. Here we review findings from our work on the nature and regulation of rhythms of expression of PER2 in two anatomically and neurochemically defined subregions of the central extended amygdala, the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) and the central nucleus of the amygdala (CEA). Daily rhythms in the expression of PER2 in these regions are coupled to those of the master circadian pacemaker, the suprachiasmatic nucleus (SCN) but, importantly, they are sensitive to homeostatic perturbations and to hormonal states that directly influence motivated behavior.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.