Finally, we computed each decoder’s

predictions for MT-pursuit correlations with the same analysis procedures we had applied to our recordings from area MT. Most of the decoding computations we used are structured as “vector averaging,” a family of decoding computations that can reproduce much of pursuit behavior, defined by S→ in Equation 1. Vector averaging computes the vector sum of MT responses (R  i) weighted by their preferred speed (s  i) and a unit vector in their preferred direction ( θ→i) in the numerator; it divides by the sum of MT responses for normalization: equation(Equation 1) S→=∑iRiθ→isi∑jRj The equations for our decoders, by using the subscripts i versus j in the numerator and denominator, include the possibility of using different populations of model neurons for the numerator and denominator. This feature allows implementation of the principle that normalization might be based on an estimate rather Gefitinib than a calculation of total population activity ( Chaisanguanthum and Lisberger, 2011). It also allows

http://www.selleckchem.com/products/AZD0530.html us to explore the new idea that there need not be neuron-neuron correlations between the populations of model units that contribute to the population vector sum and the normalization. In all models, however, we created neuron-neuron correlations within the numerator or denominator populations. There were two important ingredients of decoding models that predicted our data successfully. One was an opponent Adenosine triphosphate computation in the numerator, to create different signs of MT-pursuit correlations for neurons with preferred directions near versus opposite to the direction of target motion. The other was the lack of correlation between the model neurons that contribute to the weighted population vector in the numerator versus the normalization in the denominator, to create mostly positive MT-pursuit correlations for neurons with preferred directions within 90 degrees of target direction. Figure 4B provided a good qualitative match to the data in Figure 4A, for a form of vector averaging

that used opponent motion signals in the numerator and the sum of activity in a different population of model neurons in the denominator (Churchland and Lisberger, 2001, Huang and Lisberger, 2009 and Yang and Lisberger, 2009): equation(Equation 2) sh=∑icos(θi)Rilog2(si)k∑jRj equation(Equation 3) sv=∑isin(θi)Rilog2(si)k∑jRj equation(Equation 4) s=2sh2+sv2 We created opponent motion signals by weighting responses by the sine and cosine of preferred direction (Equations (Equation 2) and (Equation 3)), effectively computing: the response of a model unit with a given preferred direction minus the response of a model unit with the same preferred speed but the opposite preferred direction. Horizontal and vertical eye speeds sh and sv were decoded separately and combined to obtain the speed s ( Equation 4).

, 2000) and brain injury (Lowenstein et al., 1992; Santhakumar et al., 2001; Johansen

check details et al., 1987; Hsu and Buzsáki, 1993), and extensive loss of these cells following seizures or head trauma is associated with immediate granule cell hyperexcitability (Sloviter, 1983; Lowenstein et al., 1992; Toth et al., 1997). Yet whether mossy cell loss is responsible for this observed granule cell hyperexcitability is not known. According to the “dormant basket cell” hypothesis, because mossy cells normally excite inhibitory basket cells to inhibit granule cells, their loss should lead to granule cell hyperexcitability and spontaneous granule cell epileptiform behavior (Sloviter, 1991; Sloviter et al., 2003). The “irritable mossy cell” hypothesis (Santhakumar et al., 2000; Ratzliff et al.,

2002), by contrast, holds that following injury, surviving mossy cells hyperexcite granule cells by sending uncontrolled excitatory feedback. Because it was not possible to eliminate mossy cells selectively until now, researchers were unable to test these hypotheses in vivo. To determine how selective and extensive loss of mossy cells affects the excitability and behavior of dentate granule cells, we developed CT99021 molecular weight a toxin-mediated, mossy-cell-specific ablation mouse line in which mossy cells selectively express the diphtheria toxin (DT) receptor. In these mutants, following DT treatment ∼75% of mossy cells degenerate rapidly. To evaluate granule cell excitability after degeneration, we recorded local field potential (LFP) activity in vivo and assessed dentate gyrus hippocampal slices for synaptic reorganization believed Levetiracetam to be triggered by mossy cell loss (Jiao and Nadler, 2007).

Context-discrimination tasks were used to assess pattern separation. To generate hilar mossy cell-specific transgenic mice, we coinjected Cre recombinase cDNA with a minimal promoter element and a DNA fragment containing 5′-transcriptional regulatory region of calcitonin receptor-like receptor (Crlr) gene (see Figure S1A available online) into fertilized eggs from the C57BL/6N strain. After crossing with a loxP-flanked Rosa26lacZ reporter mouse, a transgenic line Cre #4688 (mossy cell/CA3-Cre) at 8 weeks old shows lacZ-positive somata exclusively in the dentate hilus and area CA3 pyramidal cells, with almost none in the dentate granule cell layer, area CA1, or neocortex ( Figures 1A and S1A). Homogenous staining of the IML where mossy cell axons terminate ( Blackstad, 1956; Amaral and Witter, 1989) reveals intense Cre-immunoreactivity (-IR) throughout the dentate hilus but not in the CA3 pyramidal cell layer ( Figure 1B). LacZ-positive cells appear in hilus/CA3c by postnatal day 9 and remain stable to at least 25 weeks, while ∼20% cells in the CA3b pyramidal cell layer are Cre-positive ( Figure S1A).

All the compounds displayed varied levels of trypanocidal activity against both T. congolense and T. b. brucei. Isometamidium (IC50 0.56 ± 0.05 ng/ml) displayed comparable trypanocidal activity to Veridium® (0.82 ± 0.25 ng/ml) and Samorin® (IC50 1.75 ± 0.50 ng/ml) against T. congolense. The blue and red isomers (IC50 7.11 ± 0.76 ng/ml and 3.63 ± 0.55 ng/ml respectively) exhibited similar trypanocidal activities, but

both were ten times less effective than Veridium® and Samorin®. The disubstituted compound was the least potent trypanocide (IC50 66.27 ± 14.37 ng/ml). For T. b. brucei, ISM and the blue isomer (IC50 9.24 ± 2.13, 12.01 ± 2.22 ng/ml respectively) had comparable activity to Veridium® (11.06 ± 3.02 ng/ml) and Samorin® (IC50 11.78 ± 4.88 ng/ml). selleck screening library Similar to T. congolense, the red isomer was 10 times less effective (IC50 202.15 ± 62.92 ng/ml) and the disubstituted compound 100 times less potent than ISM respectively (IC50 > 1000 ng/ml). The trypanocidal and prophylactic activity of Veridium®, Samorin®, purified ISM and the red and blue isomers and disubstituted compound were individually tested in vivo in mice by monitoring the survival rate after four infections with

105T. congolense IL1180 parasites ( Table 2). The first infection 24 h before treatment assessed trypanocidal activity, whereas the subsequent challenges gave an indication of prophylactic activity. All the compounds, except the disubstituted compound at a dose of 0.1 mg/kg, protected mice from the initial infection 24 h post-treatment. Samorin®, Veridium® and ISM proved to be very similar in terms of prophylactic activity in vivo, protecting mice from two challenges, the last being two Palbociclib research buy months post treatment. The disubstituted isomer, while showing no trypanocidal activity at a dose of 0.1 mg/kg, displayed similar prophylactic activity to Samorin® and Veridium® at the higher dose of 1 mg/kg. The blue isomer did not show any prophylactic effect at either of the tested doses whereas the red isomer showed partial Tenocyclidine prophylactic activity at the highest dose, one month post treatment. In the present study, the efficacy of

the commercial products Veridium® and Samorin® were compared to pure ISM, and its synthetic by-products, the red and blue isomers and the disubstituted compound (Tettey et al., 1999). Trypanocidal activity was measured in vitro and in vivo and prophylactic activity tested by survival of mice in vivo. To test the trypanocidal properties of these compounds in vitro, a new drug sensitivity test in 96-well tissue culture plates was developed which will be very useful for rapid screening of new trypanocides, or for any general assays of inhibitors or growth promoting factors. Although laboratory tools for the detection of in vitro drug sensitivity have been described previously ( Delespaux et al., 2008, Gray and Peregrine, 1993 and Hirumi, 1993), the technique proposed in this paper is simple and the least time-consuming.

Strikingly, we found that expression of EGFP under the control of the dnc

3′-UTR is highly sensitive to GW182 downregulation ( Figure 6A). EGFP signal was dramatically increased in gw182 RNAi flies, as expected since GW182 silences gene expression. On the contrary, the control construct missing the 3′UTR of dnc was insensitive to GW182 downregulation. Thus, our genetic and selleck kinase inhibitor imaging results converge in identifying DNC as a critical target of GW182 in the PDFR signaling cascade. Several studies have demonstrated that the organization of the circadian neural network responds to environmental light. While the sLNvs drive circadian behavior in the dark or under a short photoperiod, PDF-negative circadian neurons can take control of circadian behavior under constant light (LL) or a long photoperiod (Murad et al., 2007; Picot et al., 2007; Stoleru et al., 2007). This plasticity in neural hierarchy—thought to contribute to seasonal adaptation of circadian behavior (Stoleru et al., 2007)—results from photic inhibition of sLNv output and activation of PDF-negative circadian neuron output (Picot et al., 2007). Since PDF is a major sLNv output, and since our data indicate that GW182 modulates PDFR signaling through the 3′-UTR of dnc, we decided to test whether dnc expression is controlled by light. We measured EGFP-dnc 3′-UTR level of expression in control and gw182 dsRNA flies

under two conditions: LL and Chlormezanone DD ( Figure 6B). The results were striking: EGFP expression was approximately three times higher in LL than in DD in control flies, but it was not affected at all Selleckchem mTOR inhibitor by light when GW182 was downregulated. dnc 3′-UTR activity is not under circadian

control ( Figure S5), which means that its derepression in LL is not a secondary effect of LL-induced disruption of the molecular circadian pacemaker. Our results therefore indicate that DNC expression is derepressed by prolonged light exposure, which is predicted to result in decreased PDFR signaling and, therefore, a weakening of the connection between the sLNvs and its neuronal targets. Since this is GW182 dependent, and since GW182 activity is in a dynamic range in circadian neurons ( Figure 4E), it also suggests that GW182 activity is repressed in the dark (see Discussion). Does GW182 indeed impact the light-dependent reorganization of the circadian network? A method to reveal this neural plasticity is to inhibit the circadian photoreceptor cryptochrome (CRY) or its signaling pathway to allow flies to remain rhythmic under constant light (Murad et al., 2007; Picot et al., 2007; Stoleru et al., 2007). We have previously shown that we can achieve this by overexpressing MORGUE only in PDF-negative circadian neurons, leaving the PDF-positive circadian neurons unprotected from LL and, thus, arrhythmic (Murad et al., 2007).

In hypothalamic membrane preparations, a significantly higher FRET signal is observed (198 ± 27, compared to background, 100 ± 5.7, p < 0.05; Figure 8A) in agreement with relative levels of receptor mRNA (Figure 1). To test specificity, we repeated the Tr-FRET assays on membrane preparations of brain tissues from ghsr+/+ and ghsr−/− mice in parallel. Significantly higher this website FRET signals are observed

in hypothalamus from ghsr+/+ mice compared to ghsr−/− mice (p < 0.05; Figure 8B), illustrating the specificity of the Tr-FRET signal in the hypothalamus of wild-type mice. Again, Tr-FRET signals in the striatum did not reach statistical significance ( Figure 8B). We then tested for GHSR1a:DRD2 heteromers in brain slices from ghsr+/+ and ghsr−/− mice. In the hypothalamus of ghsr+/+, but not ghsr−/−, mice, confocal FRET analysis shows that GHSR1a and DRD2 are in close proximity with a relative distance of 5–6 nm (50–60 Å) and FRET intensity ranging from 0.4 to 0.6 ( Figure 8C). In the striatum, FRET intensity signals are very weak ( Figure 8C). To summarize, Tr-FRET analysis of membrane preparations

and FRET analysis from single neurons by confocal find more microscopy confirm heteromer formation between natively expressed GHSR1a and DRD2 in the hypothalamus of wild-type mice. The in vivo detection of GHSR1a:DRD2 heteromers and in vitro cell-based data led us to ask whether preventing formation of GHSR1a:DRD2 heteromers would be associated with an altered behavioral phenotype. DRD2 activation suppresses appetite (Comings et al., 1996, Epstein et al., 2007 and Stice et al., 2008). In cells coexpressing GHSR1a and DRD2 the DRD2 selective agonist old cabergoline induces a dose-dependent mobilization of Ca2+ (Figure S7A), and treating mice with cabergoline (0.5 and 2 mg/kg) results in dose-dependent suppression of food intake (Figure S7B); therefore, to test whether cabergoline’s effect was dependent upon GHSR1a and DRD2 interactions, we compared food intake in ghsr+/+ and ghsr−/− treated with cabergoline. In ghsr+/+ mice, food intake is markedly reduced within 2 hr of cabergoline treatment compared

to vehicle-treated mice (p < 0.05; Figure 8D, left graph), whereas food intake in ghsr−/− mice is unaffected by cabergoline treatment ( Figure 8D, right graph). In cells coexpressing GHSR1a and DRD2, the GHSR1a neutral antagonist, JMV2959 (Moulin et al., 2007) attenuates dopamine-induced Ca2+ mobilization (Figure 7C). To test if inhibition of DRD2 signaling by JMV2959 in cells would translate to the whole animal we treated wild-type mice with JMV2959 prior to cabergoline treatment. Indeed, cabergoline-induced suppression of food intake in ghsr+/+ mice was prevented by pretreatment with JMV2959 (0.2 mg/kg, Figure 8E, left graph), whereas food intake in cabergoline-treated ghsr−/− mice was unaffected by JMV2959 treatment ( Figure 8E, right graph).

Therefore, it was suggested that the extent and duration

of mechanical stretch may determine the cellular fate, such as death or proliferation. Our experimental findings show that acute mechanical stretch for 4 h causes continuous RASMC death. These findings may imply that an acute rise in blood pressure leads to the death of SMCs, a main component of the aortic medial layer. However, further studies click here using in vivo experimental conditions are required to elucidate whether an acute rise in blood pressure directly causes SMC death. Next, stretch-induced changes in the intracellular signaling of RASMCs were examined. It was reported that a high level of phosphorylated JNK was Modulators observed in AAD tissues, and that degeneration and tear of the aortic media CT99021 solubility dmso had occurred in the AAD lesion. (2) and (13). In addition, it was reported that inhibition of the phosphorylation of JNK lead to regression of AAD (23). In the present study, we found that acute mechanical stretch causes rapid phosphorylation of JNK and p38 (Fig. 3A and B), which may lead to SMC death. In fact, we also observed that SP600125, a JNK inhibitor, and SB203580, a p38 inhibitor, both recovered stretch-induced RASMC death evaluated based on the MTT reduction and LDH release from the cells (Fig. 5A and

B). Although we also found that ERK1/2 are phosphorylated by mechanical stretch, ERK inhibitors failed to inhibit stretch-induced tuclazepam RASMC death (data not shown). Taking these observations together, mechanical stretch causes phosphorylation of JNK and p38, which may result in SMC death that

may ultimately lead to the onset of AAD. On the other hand, a previous study showed that angiotensin II acted as an agonist for a potent inducer of AAD (1). In contrast to these findings, mechanical stretch itself, which is independent of angiotensin II stimulation, phosphorylated JNK and p38, and induced SMC death in our experiments. Although we did not measure the amount of angiotensin II in the medium, angiotensin II itself is not likely involved in JNK and p38 phosphorylation because stretch-induced AT1 receptor activation was also observed in mesenteric and renal arteries from angiotensinogen-knockout mice (24). Therefore, it is conceivable that not only agonist stimulation, but also mechanical stretch could have an important role in triggering the occurrence of AAD. ARBs are used all over the world for the treatment of patients with hypertension (25). Olmesartan, one of the ARBs, is known as an inverse agonist, which inhibits basic and stretch-induced activation of the AT1 receptor (17) and (26). In our present study, we found that olmesartan inhibited phosphorylation of JNK and p38 (Fig. 4A and B), and SMC cell death (Fig. 2) induced by acute mechanical stretch. These results suggest that olmesartan inhibits stretch-induced SMC death by suppression of phosphorylation of JNK and p38.

In view of the potential risks of tolerance and dependency and the large number of other drugs that older individuals frequently take in conjunction with insomnia medication, GW786034 clinical trial an evidence-based non-drug approach is of interest. In the

National Health Interview Libraries Survey analysis (Pearson 2006), it was reported that over 1.6 million civilian adult US citizens use complementary and alternative medicine to treat insomnia. Previous reviews have reported that non-pharmacological treatments are as effective as pharmacological therapies for older patients with insomnia (Montgomery and Dennis 2003, Montgomery and Dennis 2004, Morin et al 1999b). The non-pharmacological treatments that have been studied include providing sleep hygiene advice and cognitive What is already known on this topic: The inability

to fall asleep or maintain sleep increases with age, causing fatigue and daytime sleepiness, which impair quality of life. Although effective medications for insomnia exist, they may have side effects, including falls and cognitive impairment in older people. What this review adds: Regular aerobic or resistance exercise training significantly improves sleep quality in adults over 40 years of age. Those who exercised perceived significantly reduced time taken to fall asleep after selleck products going to bed and reduced medication use for insomnia. Exercise programs are also recommended to help prevent and treat sleep disorders (Youngstedt 2005) as well as the depression associated with these disorders among the elderly (Singh aminophylline et al 1997, Singh 2001). Having infrequent adverse effects and a low cost, participation in a community-based exercise program may be a favourable and easily accessible means of preventing and treating sleep problems among middle-aged and elderly populations. However, several meta-analyses examining the effect of exercise training on sleep (Kubitz et al 1996, Montgomery and Dennis 2002) yielded equivocal findings due to the small number of trials examined and

the limited number of participants in those trials. Since those studies were published, new evidence from additional randomised trials has become available. Therefore, the research question for this systematic review was: Does an aerobic or resistance exercise training program improve sleep quality in middle-aged and older adults with sleep problems? We searched six electronic databases (PubMed, MEDLINE, CINAHL, EMBASE, the Cochrane Library, and Chinese Electronic Periodical Service) from the earliest available date to April 2012 using keywords for insomnia (insomnia, sleep problems, sleep disorder, sleep complaints, sleep disturbance, sleep quality) and for exercise (exercise, physical activity, physical therapy). We limited the search results to full-text articles written in English or Chinese.

In this Phase III, double-blind, randomized study we assessed the immunogenicity, reactogenicity, and safety of a candidate inactivated quadrivalent split virion influenza SCH727965 datasheet vaccine (QIV).

The aim of the study was to evaluate the immunological consistency of three QIV lots, the superiority of antibody responses against the B strains in the QIV versus TIVs containing the alternate B lineage, and the non-inferior immunogenicity for QIV and TIV against shared influenza A and B strains. This Phase III, randomized, double-blind study compared the immunogenicity of QIV and TIV in adults. Reactogenicity and safety was also assessed. The study was conducted in Canada, Mexico, and the US. Eligible subjects were aged ≥18 years, were in stable health, and had not received any non-registered drug or vaccine within 30 days or any investigational or approved influenza vaccine within six months see more of the first visit. All subjects provided written informed consent. The study protocol, any amendments, informed consent and other information requiring pre-approval were reviewed and approved by national, regional, or investigational center Institutional Review Boards.

The study was conducted in accordance with Good Clinical Practice, the principles of the Declaration of Helsinki, and all regulatory requirements. Clintrials.gov NCT01196975. Subjects were scheduled to receive a single dose of either a licensed seasonal TIV (FluLaval™, GlaxoSmithKline Vaccines) or a candidate QIV. All vaccines contained 15 μg of hemagglutinin antigen (HA) of influenza A/H1N1 (A/California/7/2009) and A/H3N2 (A/Victoria/210/2009), as recommended by WHO for the 2010/11 influenza season. The TIV contained 15 μg HA of an influenza B strain from the Victoria lineage (B/Brisbane/60/2008 [B lineage recommended for 2010/11 Libraries season by WHO]) or the Yamagata lineage (B/Florida/4/2006) Sitaxentan and the QIV contained 15 μg HA of both influenza B strains. The TIVs and QIV were given as a 0.5 mL dose; the TIVs contained

0.50 μg thimerosal and the QIV was thimerosal-free. All vaccines were manufactured by GlaxoSmithKline (GSK) Biologicals in Quebec, Canada. Randomization was performed by the study sponsor using a blocking scheme, and treatment allocation at the investigator site was performed using a central randomization system on the internet. Subjects were randomized 2:2:2:1:1 to receive QIV (lot 1, 2, or 3), TIV-B Victoria (TIV-Vic) or TIV-B Yamagata (TIV-Yam). Groups had an equal distribution of subjects aged 18–64 years versus ≥65 years and a minimization algorithm was used to account for country, and influenza vaccination in the previous season. Subjects received one dose of vaccine in the deltoid of the non-dominant arm. All personnel and subjects were blind to the vaccine allocation.

Social defeat reproduces behavioral

and physiological indices of depression including disruption of CRF and NE systems (Wood and et al, 2010, Wood, 2014, Chaijale and et al, 2014, Chaijale and et al, 2013 and Russo and et al, 2012), and would likely yield important information regarding the role of NPY in depressive behavior and disorders. Several rodent models of PTSD indicate that NPY expression in the brain following stress may be associated with susceptibility selleck products to PTSD-associated impairments. For example, rats displaying extreme anxiety and arousal following exposure to predator scent stress (PSS) had lower NPY protein levels in the cortex, amygdala, hippocampus, and periaqueductal grey compared to rodents that were less impaired or to unstressed controls (Cohen et al., 2012). Injection of NPY into the hippocampus 1 h after PSS reduced the development of anxiety-like behavior, Modulators hyperarousal, and cue-elicited freezing. Additionally, NPY administration reduced the prevalence of an extreme behavioral response (Cohen et al., 2012). Delivery of NPY to the brain by intranasal (IN) infusion has been used to examine its efficacy in the single prolonged stress (SPS) model of PTSD (Serova and et al, 2013, Laukova and et al, in press and Serova and et al, 2014). Intranasal NPY can elevate

CSF concentrations to a range that reduces anxiety SNS-032 price behavior after i.c.v. administration, while also reaching multiple stress responsive brain regions and leaving plasma NPY levels unchanged (Serova and et al, 2013 and Laukova and et al, in press). Pretreatment with IN NPY slowed the development of immobility during the forced swim portion of SPS, and reduced the induction of gene expression of the NE biosynthetic enzymes, tyrosine hydroxylase and dopamine Ketanserin beta hydroxylase, in the locus coeruleus shortly after SPS (Serova et al., 2013). SPS-induced increases in plasma corticosterone

and ACTH were also attenuated by IN NPY, suggesting either less activation or more rapid recovery of the hypothalamic-pituitary-adrenal (HPA) axis (Serova et al., 2013). Intranasal NPY administered prior to or immediately after SPS led to pronounced and long-lasting effects on the development of behavioral, neuroendocrine, and molecular impairments associated with PTSD. NPY greatly attenuated, and in many cases prevented, increases in anxiety, hyperarousal, and depression-like behavior observed 1–2 weeks after exposure to traumatic stress (Serova et al., 2013). NPY prevented SPS-triggered induction of CRF, glucocorticoid receptor (GR), and FKBP5 mRNAs and the reduction in phosphorylated-GR in the mediobasal hypothalamus (Laukova et al., in press). NPY also increased the expression and phosphorylation of GR in the hippocampus (Laukova et al., in press).

This was the case in every trial for all animals (Figure 2A). Which aspects of the motor and sensory

activity determine the timing of the jump? We found that the time at which the cocontraction ended (triggering) was highly correlated with take-off (ρ = 0.95, p < 10−9). Moreover, this correlation exists regardless of l/|v|, since the partial correlation coefficient between these two variables controlling for l/|v| remained high (ρpart = 0.94, p < 10−9). On average take-off occurred 36 ms after triggering (SD: 15, nL = 4, nT = 29; Figure 2B, dashed line) and 90% of the variance in the timing of take-off could be explained by the timing of triggering. At the sensory level, we found that the timing of the DCMD peak firing Selleckchem Buparlisib rate and take-off were highly correlated as well (ρ = 0.87, p < 10−9) and that the partial correlation coefficient between these variables controlling for l/|v| also remained high (ρpart = 0.73, p = 9.2 × 10−8). Etoposide datasheet Locusts took off on average 70 ms (SD: 13) after the DCMD firing rate peaked, regardless of l/|v| (Figure 2C, dashed line) and the timing of the peak accounted for 75% of the variance of the take-off time. Not all looming stimuli led to a final take-off. Thus,

locusts jumped with a median probability of 32%. The jump probability was significantly reduced compared to that of animals without a telemetry backpack (Fotowat and Gabbiani, 2007; median: 64%, pKWT = 0.003). Figure 3 shows a trial in which the same locust as in Figure 1 did not jump (Movie S2). It started preparing by cocontracting its hindleg

flexor and extensor muscles. However, compared to jump trials, the cocontraction started late, such that after a few spikes in the extensor, the many looming stimulus reached its full size, the DCMD firing rate declined, and the cocontraction ended. This was the case in 85% of trials without take-off, whereas in the remaining 15% the cocontraction failed to initiate altogether. Across animals, we found that cocontraction onset occurred significantly earlier relative to collision in jump trials (Figure 4A), whereas the timing of the DCMD peak itself did not change (Figure 4B). Thus, while the DCMD peak time predicts the time of take-off, it fails to predict its occurrence. Since cocontraction started earlier in jump trials, the number of extensor spikes was also significantly higher (Figure 4C). In contrast, there was no difference in the total number of DCMD spikes between jump and no-jump trials (Figure 4D), although the peak DCMD firing rate was higher in jump trials (Figure S2A). However, we found that if we started counting the DCMD spikes from cocontraction onset rather than stimulus onset (shaded areas in Figure 1 and Figure 3), their number was significantly higher in jump trials (Figure 4E). Furthermore, the number of DCMD spikes from cocontraction onset was highly correlated with the number of extensor spikes (ρ = 0.73, p < 10−9, Figure 4F), such that on average 4.