For instance, activated Arf6 binds the PI(4)P-5 kinase (such as the neuronally expressed PIPKIγ661), which synthesizes PI(4,5)P2. AP-2 adaptor is then recruited to the plasma membrane by binding PI(4,5)P2 (Bairstow et al., 2006 and Krauss

et al., 2006). Modulating lipid composition aids in regulating vesicle budding. Vesicle or tubule formation requires deformation of the lipid bilayer and curvature. For a small diameter vesicle (diameter of ∼50 nm), the curvature is substantial and not all lipids can be accommodated into such a curved configuration: lipids that cannot be accommodated into a small vesicle are therefore systematically excluded from forming vesicles. Additionally, regulation of lipid composition provides a possible mechanism for regulating cargo entry, as some proteins associate preferentially with certain types Navitoclax research buy of lipids. The best studied examples of these are “lipid raft” lipids, including cholesterol and glycosphingolipids (Rajendran and Simons, 2005), which contain straight saturated fatty acid chains and prefer planar membranes over highly curved ones. see more The lipid raft concept has been controversial since it was introduced several decades ago (Munro, 2003). Nevertheless, consensus has emerged that lipids are not

homogeneously distributed in membranes and that domains with differing lipid and protein composition coexist side-by-side in cellular Mephenoxalone membranes (Simons and Gerl, 2010 and Simons and Ikonen, 1997). Curvature of membranes into small vesicles does not occur spontaneously, and several classes of proteins have been found to bend membranes (often using banana-shaped BAR domains) and induce tubulation of liposomes in vitro. These proteins play important roles in vesicle transport. A growing number of gene families are implicated in membrane bending, among them the EHD protein family (Daumke et al., 2007), the sorting nexins, and

others (Prinz and Hinshaw, 2009). Once the membrane is deformed by the action of such proteins, other proteins preferentially bind to membranes of a certain curvature and are therefore recruited to nascent vesicles or tubules. It was shown a few years ago that the enzymatic activity of some proteins, such as Arf1, is dependent on membrane curvature (Antonny, 2011 and Bigay et al., 2003). Some regulators are only active on planar membranes or only on highly curved vesicle membranes. It is easily seen how linking enzymatic activity to lipid composition and curvature can restrict activity to a small specific subsets of membranes and guard against random fission and fusion events. Subsequently, regulatory platforms consisting of multiple interacting proteins are assembled in a sequential fashion. The GTP-bound form of the Rab GTPases bind effectors that mediate the downstream action of the pathway (Horgan and McCaffrey, 2011).

Cost-effectiveness selleck chemicals analysis typically involves measures such as dollars per quality adjusted life year (QALY) gained or disability adjusted life year (DALY) prevented to quantify the financial burden against health gain.7 and 8 Given this background, the preponderance of efficacy studies in Tai Ji Quan research is understandable. If efficacy cannot be demonstrated it makes little sense to try to implement a program outside the research

setting (i.e., determine effectiveness) and less sense to consider any potential cost-benefits issues as there are no discernable benefits. Alternatively, the ideal process should begin with well-designed RCTs that drive the development of programs that can be implemented in community settings and that maximize health improvement per dollar spent compared to existing interventions.9 and 10 click here Unfortunately, this logical sequence has been stalled at the first step by the questionable quality of many RCTs and the paucity of coordinated research programs on Tai Ji Quan that go beyond one-time, isolated efficacy studies. The problem is highlighted by the relative numbers of different types of reports in the medical

and healthcare literature. Table 1 summarizes the results of a search on PubMed/Medline, the largest medical literature resource in the world, conducted in September 2013 using all variations of the term Tai Ji Quan. A total of 710 articles were returned, of which only nine were published prior to 1990 (including 2 RCTs). Given that Tai Ji Quan was only introduced into the American mainstream in the 1970s, the lack of scientific interest before 1990 in what may have been considered, at best, a type of complementary and alternative medicine or, at worst, a fringe activity or quackery is not surprising. However, Tai Ji Quan continued

to spread to the point that according to a National Health Interview Survey report published PDK4 in 2007, almost 2.5 million Americans indicated they had practiced Ti Ji Quan in the previous year.11 Paralleling participant growth was interest from the scientific and medical communities, spurred by the pioneering work of Wolf,12, 13 and 14 as seen in the number of Tai Ji Quan-related publications since 1990, including 173 RCTs and 162 reviews. However, it is instructive to note the significant increase in the number of review papers, especially over the past 5 years, compared to the growth of RCTs. Systematic and critical reviews, often involving meta-analyses, are designed to summarize the current state of knowledge in a field and to impose some order on disparate findings. It is clear from the conclusions of the most recent reviews that the field of Tai Ji Quan research is very active but in disarray.

Although not as pathogenic as Ancylostoma caninum, heavy infections in young dogs may result in blood loss ( Rep, 1980) and hypoproteinemia ( Miller, 1968). However, the most significant concern with A. braziliense is its ability to cause cutaneous larva migrans in both dogs ( Vetter and Leegwater-vd Linden, 1977, Vetter and van der Linden, 1977a, Vetter and van der Linden, 1977b and Bowman et al., 2010) and humans ( Brenner and Patel, Y-27632 concentration 2003, Patel et al., 2008 and Purdy et al., 2011). Of the hookworm larvae,

A. braziliense tends to be more invasive by cutaneous penetration and shows the greatest enzyme activity for breaking down structures of the skin ( Hotez et al., 1992), thus allowing the larvae to enter by direct contact with intact skin and mucous membranes. Not only has A. braziliense been associated with cutaneous Olaparib purchase larva migrans in humans, but also migration to the lungs ( Butland and Coulson, 1985) and oral mucosa ( Damante et al., 2011). Even though the parasite is more common in the tropical regions of the world, it has also been reported in non tropical settings ( Herbener and Borak, 1988), suggesting the need for control outside the areas typically considered endemic. Therefore, effective control of A. braziliense in dogs is important because

of its potential pathogenicity in dogs and zoonotic potential for cutaneous larva migrans in humans. Milbemycin oxime is a macrocyclic lactone that is efficacious against infections of A. caninum ( Blagburn et al., 1992 and Niamatali et al., 1992), but no studies have been done specifically investigating effectiveness against A. braziliense. We hypothesized that milbemycin oxime would be over 90% efficacious when administered as a single treatment to dogs infected with A. braziliense. The study was a randomized, blinded, placebo controlled laboratory study using

naturally infected dogs conducted in compliance with GCP (VICH GL9), South African animal welfare regulations, as stipulated in the “National Code for Animal Use in Research, Education, Metalloexopeptidase Diagnosis and Testing of Drugs and Related Substances in South Africa”. The protocol was submitted to the ClinVet Animal Ethics Committee (CAEC), the composition of which was in compliance with the National Code, for approval. In addition, the protocol was reviewed and approved by the Novartis Animal Health US, Inc. Institutional Animal Care and Use Committee. Thirty-six hookworm infected dogs (21 males and 15 females), a minimum of 10 weeks of age and of any pure or mixed breed were randomly assigned to cages at the beginning of acclimation. Animals were purchased from owners who were fully informed of the nature of the study. Each dog was identified by a unique number on a collar tag. All purchase contracts indicated each animal’s origin and procurement records traceable to each animal by identification number.

Even in ideal situations, the optical detection of the membrane potential can only be carried out with relatively few emitted photons. Because of this, for the signal to be distinct from the photon shot noise, one typically needs to use very efficient chromophores, very strong light sources, or extensive Dabrafenib mw temporal or spatial averaging. Unfortunately, despite its great strength as an insulating layer and in maintaining cellular integrity, the plasma membrane is also a very delicate part of the cell and does not tolerate intense illumination. The photodamage associated with excited state reactions,

such as the generation of disruptive oxygen free radicals and other triplet state reactions, or simply by local heating, following photoabsorption by the chromophores used to measure the voltage signals, can easily

compromise the integrity of the membrane and kill the cell. Indeed, some sort of photodamage is present in essentially all voltage imaging measurements and is find protocol normally the reason voltage imaging experiments are terminated. To make this situation worse, neurons, like most mammalian cells, have a significant complement of endogenous chromophores, such as flavins, cryptochromes, and phorphyrins, that absorb visible light and, in some cases, are even located near the membrane. So even illuminating unstained neurons can lead to the generation of oxygen free radicals, damaging the membrane and altering membrane conductances, and may even result in membrane perforations ( Hirase et al., 2002). This endogenous photodamage is so prevalent that one sometimes wonders whether neurons have light-sensing machinery, as unicellular organisms do, to monitor circadian light changes. A third constraint arises from the fact that most of the membranes in cells are actually internal membranes. The plasma membrane, the only one across which the neuronal

membrane potential exists, is only a small proportion of the total membrane surface in the neuron. Thus, any chromophore that binds indiscriminately to membranes will mostly bind to internal membranes, which have no direct sensitivity to the plasma membrane voltage, and as a result, these Sitaxentan chromophores will merely contribute to the background noise of the measurement. This is quite a significant problem, one that again does not exist for calcium imaging, where the intracellular calcium eventually equilibrates by diffusion in the cytoplasm, in principle making every molecule of chromophore in the cytosol a possible contributor to measuring the signal. For voltage imaging, the desire to target only the plasma membrane and yet avoid internal membranes compounds the already strong localization requirements.

The structural images were then averaged together for displaying the functional data. Event-related BOLD responses were analyzed using a general linear model (GLM). Activity related to each trial was modeled with a stick function, representing the onset of the first image, convolved with the canonical hemodynamic response function. Serial correlations in the time series were accounted for using the autoregressive model [AR(1)]. A high-pass filter of 128 s was used. CHIR-99021 There was a covariate of interest for each confidence bin (i.e., 1–6) for each of the four trial types (i.e., scene/face different/same) for each of the eight

runs. Covariates of no interest were the six motion covariates for each run estimated during the realignment step of preprocessing. Contrast coefficients were weighted to account for different numbers of trial types in each run. Contrast images from first-level analyses were then entered into second-level analyses. 3DClustSim (Cox, 1996; http://afni.nimh.nih.gov/pub/dist/doc/program_help/3dClustSim.html) was used to determine the cluster correction for p < 0.05 across the whole brain (p < 0.001 and k = 86 voxels). We opted to define the hippocampal ROI functionally, rather than structurally, because it would give us more power to detect hippocampal involvement. Previous studies have consistently found

posterior, but not anterior, CH5424802 cost hippocampal involvement in scene perception (e.g., Lee and Rudebeck, 2010; Lee et al., 2008; Mundy et al., 2012), which is consistent with work in the rodent implicating the dorsal (septal) hippocampus in spatial context memory (Fanselow and Dong, 2010 and Moser and Moser, 1998). Accordingly, averaging over the entire anterior-posterior extent of the hippocampus could have reduced the power to detect hippocampal involvement. To save the functional clusters as ROIs, we used MarsBaR (M. Brett, J.-L. Anton, R. Valabregue, and J.-P. Poline, only International Conference on Functional Mapping of the Human Brain, 2002). Parameter estimates were extracted and averaged

for the voxels within the cluster for each confidence bin. Responses were collapsed across “same” and “different” trials because an insufficient number of misses prevented an examination of only “different” trials for confidence responses 1–3. For the analysis with “different” trials only, we restricted the analysis to response bins “4,” “5,” and “6” because there were adequate trial numbers in those bins for every participant (i.e., every participant met the criterion of at least 10 trials in each response bin; average number of trials were 20, 32, and 42 for “4,” “5,” and “6” response bins, respectively). Because only 1 participant met the criterion of more than 10 responses in each bin for the “1,” “2,” and “3” responses on “different” trials, we could not reliably extract parameter estimates for those responses (average number of trials were 6, 9, and 10 for “1,” “2,” and “3” responses, respectively). See Figure S1.

, 2012). It is possible that BGNT2 acts to shape the Slit gradient in the AOB or modulate Slit interaction with Robo2 receptors on VNO axons, and this phenotype will need to be characterized more closely. These exciting results raise many important questions. Androgen Receptor Antagonist ic50 Are Slits the only midline axon guidance proteins binding to α-DG? Recent work has demonstrated that DGN-1, the C. elegans homolog of α-DG, is required for appropriate development

of the lumbar commissure ( Johnson and Kramer, 2012; Figure 3C). Interestingly, in this system, genetic evidence suggests that the α-DG pathway is not only linked to Slit but also to UNC-6/netrin-1. These data support a role for dystroglycans in axon guidance but Tyrosine Kinase Inhibitor Library manufacturer also suggest that netrin-1 localization might be perturbed in the α-DG and B3GNT1 mutants. Further analysis will be required to determine if other Slit responsive axons are misguided in α-DG/B3GNT1/ISPD mutants. Interestingly, hindbrain pontine neurons, which

are commissural, express Robo receptors, α-DG, Large and Fukutin, and in all the corresponding mutants (as in WWS patients) pontine neurons do not migrate properly toward the floor plate (see references in Waite et al., 2012). Undoubtedly, this exciting study opens new perspectives in the axon guidance field and beyond, as Slit/Robo signaling regulate cell-cell interaction in many developing organs and in tumor cells and similarly, many of the B3gnt enzymes have also been shown to play a crucial role in tumorigenesis in many different cancers. “
“The mammalian auditory sensory organ, the cochlea, has exceptional sensitivity with extraordinary frequency selectivity and enormous dynamic range, all of which are required for detecting and processing a variety of sounds. When sounds enter the ear canal, the air pressure oscillation causes the flexible ear drum to vibrate. This vibration reaches the cochlea over through the middle-ear

ossicular chain, including the stapes, which displaces the cochlear fluid and partition from their equilibrium positions (Figure 1A). The vibration starts at the cochlea’s base and travels along the spiral basilar membrane toward the apex, its magnitude increasing and speed decreasing. The wave reaches a maximum amplitude at a location along the basilar membrane that depends on the stimulus frequency (von Békésy, 1970). This location at the response peak is called the “best-frequency” (BF) place. Sensory hair cells at the BF location effectively detect the vibration through their mechanotransduction channels; the magnitude, frequency, and timing information of sounds are subsequently encoded in electrical pulses of the auditory nerve and transmitted to the brain. The cochlea can detect sounds at levels that induce stapes vibrations that are less than a picometer (1 × 10−12 m) (Ren et al.

Of course, these cannot be strictly segregated, and it should be kept in mind that neurons can participate within several networks; Selleck ABT 888 for example, neurons acting with the network underlying social behavior can also contribute to processing within the networks involved in stress and anxiety. Following an early definition proposed by Kupfermann (1979), neuromodulation, unlike

conventional neurotransmission, does not simply excite or inhibit an electrically excitable cell, but is rather involved in altering the effects of other events occurring at the cell. Most reports on the neuromodulatory effects of AVP and OT, however, have up to now only studied effects of external application of these neuropeptides, often resulting in robust changes in spontaneous neuronal activity. However click here such “spontaneous” activity is typically

generated under precise given circumstances in vitro (e.g., changes in external concentrations of Ca2+ or K+) that in vivo may depend on conventional neurotransmission. In strictest sense, these studies can therefore not distinguish between a role of OT and VP as conventional neurotransmitters or as neuromodulators. In this context it is important to keep in mind that neuropeptides typically are thought to be coreleased with other classical neurotransmitters such as glutamate or GABA only at higher frequencies of stimulation (Hökfelt, 1991). Consistently, our findings with the blue light-induced stimulation of endogenous release of oxytocin suggest corelease with glutamate (Knobloch et al., 2012) and a similar scenario may apply for vasopressin. The development of optogenetic methods to specifically stimulate OT and AVP containing projections can here provide a most valuable, and possibly even crucial, tool to dissect the precise neuromodulatory roles of these neuropeptides in situ. AVP and/or OTRs are expressed in different regions of the main and accessory olfactory systems. In the main olfactory epithelium, mRNA for both V1a and V1b receptors has been detected

(Levasseur et al., 2004). Furthermore, in an immortalized cell line displaying the features of immature, migrating olfactory neurons (GN11), activation of OTRs led to the accumulation of inositol phosphates and to the inhibition of an inwardly rectifying potassium currents (Gravati et al., 2010). No studies seem to have addressed a role in the Cell press pheromone-sensitive epithelium of the vomeronasal organ. At the next level, V1a&bRs as well as OTRs are expressed in both the main (MOB) and accessory olfactory bulb (AOB) (Tobin et al., 2010; Vaccari et al., 1998). Although the MOB and AOB receive distinct inputs from, respectively, the olfactory epithelium and vomeronasal organ, their anatomical organizations appear very similar. In both bulbs, mitral cells (MCs) constitute the main relay neurons. Dendrites of mitral cells make excitatory contact with dendrites of local granule cells (GCs) and in return receive inhibitory dendritic inputs from GCs (Figure 3A).

These parallels have led to the hypothesis that Pcdhs, like Dscams, may provide C59 wnt a source of cell surface diversity for neurite self-recognition and self-avoidance ( Zipursky and Sanes, 2010). This possibility is supported by our recent finding of dendritic self-avoidance defects in Pcdhg deficient mice ( Lefebvre et al., 2012). A fundamental difference, however, resides in the fact that each Dscam1 isoform appears to be functionally equivalent, whereas certain Pcdhs, such as the C-type isoforms, have unique roles as we show here. Unlike Dscam1 where isoform diversity is generated by alternative

splicing, differential expression of Pcdh isoforms is regulated by alternative promoter choice ( Tasic et al., 2002; Wang et al., 2002a), which provides precise spatial and temporal controls over gene RO4929097 research buy expression. As noted earlier, the C-type isoforms are phylogenetically unique among Pcdhs and exhibit distinct expression patterns. It remains to be seen whether just one of the three C-type

genes is solely responsible for this function, or whether they work synergistically. We note that the two other C-type isoforms in the Pcdha cluster (Pcdhac1 and Pcdhac2) are dispensable for neuronal survival ( Hasegawa et al., 2008; Katori et al., 2009), but they may play other specific roles yet to be identified. Further functional studies specifically targeting each of these C-type isoforms would be required to address these possibilities. All animal experimental procedures were in accordance with protocols approved by the Institutional Animal Care and Use Committees (IACUC) of Columbia University Medical Center and Harvard University. Detailed Experimental Procedures can be found in the Supplemental Information with this article online. We thank Rick Myers, Rolf Kemler, Greg Philips, Andreas Kolb, and Philippe Soriano for providing essential reagents, Monica Carrasco, Flo Pauli, Jiangwen Zhang, Hilary Bowden, and Amy Kirner

for technical assistance, and Tom Jessell, George Mentis, Angel de Blas, Larry Shapiro, and members of the Maniatis laboratory for advice and discussion. This work is funded by NIH grants NS047357 to F.J.A., R01NS029169 to J.R.S., and R01NS043915 to T.M. “
“The elongated hippocampus communicates with the neocortex via the entorhinal cortex interface (Witter et al., those 1989). Both hippocampal “representation” of neocortical information and rerouting of hippocampal messages to the neocortex are topographically organized (cf. Amaral and Lavenex, 2007; Witter et al., 1989). The septal (or “dorsal,” DH) and intermediate (IH, or posterior) segments receive visuospatial inputs indirectly mainly via the dorsolateral band of the medial entorhinal cortex, while the temporal segment (or “ventral hippocampus,” VH) from the ventromedial band of the entorhinal cortex (Dolorfo and Amaral, 1998; Witter et al., 1989).

The expression level of CBP remained unaffected in EcRDN-expressing (n = 7; Figure S4G) or BrmDN-expressing (n = 13; Figure S4H) ddaC neurons. Therefore, the expressions of Brm, CBP, and EcR-B1 are independent XAV-939 manufacturer of each other. Collectively, CBP, like Brm, specifically regulates activation of Sox14 expression, but not EcR-B1 expression, during ddaC pruning. Given that CBP can acetylate histones in Drosophila embryos ( Das et al., 2009 and Tie et al., 2009), we next assessed whether CBP mediates histone acetylation in ddaC neurons. Among 18 available antibodies against various histone H3 lysine acetylation marks that we examined, six of them (K4, K9, K18,

K23, K27, and K36) exhibited prominent staining signals in sensory neurons ( Figure 6E; Figure S5A). CBP is

required for the acetylation of H3K4, H3K18, H3K27, and H3K36 marks, but not for the acetylation of H3K9 and H3K23 marks in ddaC neurons ( Figure 6F; Figure S5A). We then focused on H3K27Ac, an epigenetic mark associated this website with activation of gene transcription ( Tie et al., 2009). In contrast to its abundance in wild-type ddaC neurons (n = 11; Figure 6E), H3K27Ac was absent in all CBP RNAi ddaC nuclei (n = 12; Figures 6F and 6H). H3K27Ac levels remained abundant in all EcRDN (n = 8; Figure S5B) and BrmDN-overexpressing (n = 13; Figure S5B) ddaC neurons. Similarly, H3K27Ac levels were largely abolished in ecdysone-treated S2 cells upon CBP knockdown using double-stranded RNA (dsRNA; Figure 7G), whereas its

levels remained abundant in EcR RNAi, brm RNAi, and GFP RNAi control ( Figure 7H). Thus, CBP is a major HAT MTMR9 that predominantly mediates the acetylation of H3K27 in ddaC neurons and ecdysone-treated S2 cells. We reasoned that if the HAT activity of CBP is required for ddaC dendrite pruning, overexpression of certain HDAC proteins that can reverse CBP-mediated histone acetylation would be expected to resemble CBP knockdown phenotypes. Among potential Drosophila HDACs, overexpression transgenes for five of them were available. We overexpressed Grunge/Atrophin, Rpd3, Sir2, HDAC3, and HDAC6 and examined their effects on dendrite pruning of ddaC neurons. Among these HDACs, we found that Rpd3, the class I HDAC homologous to mammalian HDAC1/2, is involved in ddaC dendrite pruning. Overexpression of Rpd3 led to a partial but consistent defect in ddaC dendrite pruning (44%, n = 83; Figures 6A and 6A′). Strikingly, overexpression of Rpd3 also resulted in significant downregulation of Sox14 expression (n = 25; Figures 6C and 6D), as well as a strong reduction of H3K27Ac levels (n = 10; Figures 6G and 6H) in ddaC neurons, without obviously disturbing CBP expression levels (n = 15; Figure S5C). Interestingly, the Rpd3 levels were increased in CBP RNAi ddaC neurons (n = 11; Figures 6J and 6L).

For all frequencies, there was a significant left-right and flexor-extensor alternation (preferred direction around 0.5 in the circular plots; Figures 3D and 3E). The increased variability in burst parameters (see above) likely contributes to the slightly weaker left-right coupling in Shox2-vGluT2Δ/Δ cords (seen as shorter r-vectors

at lower frequencies of locomotion Figures 3D and 3E). At higher speeds of locomotion, the variability decreased but coupling was unaltered. Flexor-extensor coupling was not significantly different at any locomotor frequency. These findings underscore a role for Chx10off Shox2 INs in rhythm generation (a change in frequency) but with little to no effect on left-right and flexor-extensor coordination. However, in addition to influencing locomotor frequency, elimination of Shox2 INs also affected the stability of the rhythm, in a manner similar selleck chemical to that seen when all V2a neurons were ablated (Crone et al., 2008), and when the Shox2+ GW786034 price V2a neurons are eliminated (this study). The reduction in locomotor frequency is seen in Shox2-vGluT2Δ/Δ mice, where both Shox2+ V2a INs and Shox2+ non-V2a INs are silenced, but not in Shox2-Chx10DTA mice, where Shox2+ V2a INs alone

are ablated, suggesting a specific role for Shox2+ non-V2a INs in rhythm generation. Bath application of locomotor drugs exposes all spinal neurons to neural excitants uniformly and tonically, which likely is not the case in vivo. To test the locomotor phenotype of Shox2-vGluT2Δ/Δ mice in a more physiological context, we evaluated locomotor-like activity induced by brainstem stimulation, an efficient way of evoking bouts of locomotor activity. Rhythmic ventral root bursting was elicited by descending fiber stimulation in both control and Shox2-vGluT2Δ/Δ spinal cords ( Figures 3G and 3H). In controls, heptaminol burst frequency increased with stimulus strength ( Figure 3I). However, locomotor frequency in Shox2- vGluT2Δ/Δ cords was slower than controls at all stimulus intensities, apart from the lowest ( Figure 3I). Additionally, in Shox2-vGluT2Δ/Δ spinal cords locomotor frequency failed to increase with increasing stimulus

intensity ( Figure 3I). Left-right and flexor-extensor activities were in alternation (offset ∼180°) in both control and Shox2-vGluT2Δ/Δ mice at all stimulation intensities tested ( Figures 3J and 3K). These experiments show that Shox2 INs may be involved in mediating the descending locomotor drive and/or generating the rhythmic activity in the spinal cord. Although some of the reduction in frequency seen in neural-evoked locomotion may be due to a loss of Shox2-related descending drive, the drug-induced method to evoke locomotor-like activity bypasses the neural-evoked pathways for initiating locomotor-like activity. Together, the lower drug-evoked and stimulus-evoked locomotor frequencies seen in Shox2-vGluT2Δ/Δ cords as compared to controls suggest that spinal Shox2 INs play a significant role in rhythm generation.