Since NGL-2 affects synaptic transmission selectively in the SR pathway but does not affect the properties of individual synapses, we sought to determine whether NGL-2 exerts a cell-autonomous and pathway-specific effect on synapse density. We investigated the role of postsynaptic NGL-2 in regulating spine density by knocking down NGL-2 in a subset of CA1 pyramidal

cells. We electroporated the GFP-containing shNGL2 or control plasmids into embryonic day 15 (E15) mouse embryos (Figure 5A). Animals were perfused at P13–P15, the brains were sectioned and immunostained for GFP (Figure 5B), and spine density was analyzed on secondary apical dendrites in the stratum find more radiatum (Figure 5C). Consistent with the electrophysiological experiments, we found that NGL-2 knockdown caused a significant decrease in spine density on CA1 dendrites in stratum radiatum as compared to the GFP control (Figures 5D and 5G). To determine whether

the effect on spine density was selective to the dendritic segment traversing the SR, we also measured CA1 spine density on secondary apical dendrites in the SLM and found that shNGL2 expression did not affect spine density in this domain (Figures Idelalisib molecular weight 5D and 5H). Thus, postsynaptic knockdown of NGL-2 selectively affects spine density in the stratum radiatum without affecting spine density in the SLM, indicating that a major role of NGL-2 is to regulate synapse density in the SR pathway.

To identify the domains of NGL-2 that mediate its synaptic effects, we coelectroporated shNGL2 with an shRNA-insensitive full-length NGL2∗ or domain deletion mutants and quantified spine density in the SR and SLM (Figures 5E–5H). Expressing NGL2∗ rescued spine density back to control levels on dendrites in the SR (Figures 5F and 5G). We observed no change in spine density in the SLM (Figures 5F and 5H), which is consistent with the targeting of NGL-2 to SR synapses. To determine whether the LRR and PDZ-binding domains of NGL-2 contribute to the spine effects of NGL-2, we generated shRNA-resistant deletion mutants NGL2∗ΔLRR and NGL2∗ΔPDZ (Figure 5E). Like the full-length rescue construct, both mutants are insensitive to shNGL2 (Figure S3B) and reach the surface of HEK293T out cells (Figure S3C). Unlike the full-length NGL2∗, neither NGL2∗ΔLRR nor NGL2∗ΔPDZ could rescue the shNGL2-mediated decrease in spine density in SR (Figures 5F and 5G). Furthermore, neither mutant had an effect in SLM (Figures 5F and 5H). Thus, both the LRR and PDZ-binding domains are required for NGL-2-mediated regulation of spine density in CA1. To further explore the roles of the LRR and PDZ-binding domains in excitatory synapse formation, we overexpressed these mutants, full-length NGL2∗ or EGFP control in cultured hippocampal neurons and analyzed excitatory synapse density by staining for excitatory synapse markers PSD-95 and VGlut1 (Figure S3A).

Notably, LBD mutations in certain Kainate receptors also reduce cell-surface expression in cultured cells (Valluru et al., 2005). While IR8a (and IR25a) may associate with unknown ligands important for trafficking, we favor instead a model in which the conformation of coreceptor LBDs contributes to a scaffold for correct assembly of an IR complex to ensure only functional heteromers reach sensory cilia. VX770 In contrast to IR8a and IR25a, evolution of odor-specific IRs, such as IR84a and IR75a, was accompanied by a significant reduction in the structural complexity, as these proteins lack an ATD and bear only short, and apparently dispensable,

cytosolic C termini. Divergent LBDs and pore filters in these proteins appear to confer specificity of odor recognition and ion conduction properties of IR-receptor complexes, respectively. Traces of ancestral glutamate-binding mechanisms are detectable, however, as we show that a glutamate-conjugating arginine is conserved

and essential in IR84a for recognition of its odor ligand, phenylacetaldehyde. Odor-specific IR sequences may provide a valuable source of natural (and functional) “site-directed mutants” to understand how the ion conduction and other properties of these ligand-gated ion channels are specified at the molecular level. Our reconstitution of olfactory responses using a combination of three distinct IRs (IR25a, IR76a, and IR76b) highlights a further level of sophistication in how these proteins assemble into functional odor-sensing complexes. While IR76a is very likely to define ligand-specificity, the precise contributions of IR25a and a second putative SKI-606 in vitro coreceptor, IR76b, have not yet been resolved. It is possible that IR76b, which is more closely related to odor-specific IRs than to IR25a or IR8a, recognizes an unknown chemical ligand, whose copresence with phenylethyl amine in an odor blend could lead to synergistic or diminished neuronal responsiveness. Further variations

in IR complexes are apparent. For example, IR25a is likely to have IR76b-independent roles as a coreceptor for sacculus and aristal odor-specific IRs, as not the latter receptor is not expressed in these structures (Benton et al., 2009). Moreover, the ammonia receptor in ac1 is independent of both IR8a and IR25a. Thus, while OR-expressing neurons in vertebrates and insects encode odor stimuli through the activity of singularly expressed odor-specific receptors (Touhara and Vosshall, 2009), the IRs appear to function in “combinatorial codes” within individual OSNs. These may define unique ligand sensitivities and signaling dynamics akin to the heteromer-specific properties of iGluRs in synaptic localization and signaling (Coussen, 2009, Greger et al., 2007 and Kohr, 2006). In contrast to iGluRs (Walker et al., 2006), however, IRs do not appear to depend upon additional accessory proteins, such as TARPs (Tomita, 2010), for cell surface expression or function.

Competitive blockade of group I and group II mGluRs with the LY341495 (100 μM) (Kingston et al., 1998) also failed to prevent bicuculline-induced downregulation of surface GluA1 and GluA2/3 (Figures S1C and S1D). The failure of CP and MCPG or LY341495 to block scaling to bicuculline suggests that mGluR activation is not due to glutamate

released at synapses or glutamate that might accumulate in the medium. To further examine this issue, we added glutamate-pyruvate transaminase (GPT) to the medium during Ku-0059436 chronic bicuculline treatment at a concentration reported to prevent local accumulation of glutamate at synapses (Matthews et al., 2000 and Pula et al., 2004). The Kd of GPT for glutamate is ∼8 μM and this is close to the measured level of glutamate in the medium of our

cultures (∼7 μM). GPT did not alter the effect of chronic bicuculline to downregulate surface GluA1 and GluA2/3 (Figures S1E and S1F). Effects of group I mGluR Selleckchem LY2157299 antagonists on bicuculline-evoked scaling were examined in parallel using electrophysiological recordings. Chronic treatment with Bay and MPEP produced an increase in the miniature excitatory postsynaptic current (mEPSC) amplitudes (control 20.9 ± 1.1 pA; n = 24 cells versus Bay/MPEP 26.7 ± 1.9 pA; n = 21 cells; #p < 0.05), and blocked the effect of bicuculline (bic 14.1 ± 0.2 pA; n = 28 cells versus bic/Bay/MPEP 25.7 ± 2.0 pA; n = 18 cells) (Figures 1E and 1F). By contrast, chronic CP and MCPG did not block the effect of bicuculline (amp: 13.5 ± 0.4 pA, ∗∗p < 0.01; frequency: 22.8 ± 2.6 Hz, n = 22 cells), and did not produce an increase in the basal mEPSC amplitude (21.8 ± 0.9 pA, n = 11 cells, Figures 1E and 1F) or frequency (22.0 ± 2.8 Hz, n = 11 cells). The cumulative histogram ADP ribosylation factor of mEPSCs indicates that Bay 36-7620 and MPEP produced a multiplicative increase of amplitudes, suggesting the antagonists produce a scaling up of relative synaptic weights (Turrigiano and Nelson, 2000). Chronic Bay and MPEP also increased the frequency of mEPSCs (control 23.4 ± 2.6 Hz;

n = 24 cells versus Bay/MPEP 36.4 ± 4.4 Hz; n = 21 cells; #p < 0.05). This is consistent with either a presynaptic action of group I mGluRs or the possibility that Bay and MPEP convert silent synapses to active synapses. To assess if Homer1a can activate group I mGluRs in cortical neurons to downregulate surface AMPARs, we expressed Homer1a transgene by Sindbis virus infection for 24 hr, and assayed surface AMPARs by biotinylation and IHC. We compared effects of Homer1a with that of Arc (Shepherd et al., 2006). Neurons were treated with tetrodotoxin (TTX, 1 μM) to reduce native expression of Homer1a and Arc, and thereby isolate the action of the transgenes. Surface GluA1 and GluA2/3 were reduced in neurons that expressed Homer1a or Arc, compared to GFP (Figures 2A and 2B).

He first determines the species, sex, and

mating status of the target, primarily by sensing volatile and contact pheromones. These chemical signals can be either stimulatory (from females) or inhibitory (from other males) and are thought to activate hard-wired circuits to control the decision to court ( Dickson, 2008). However, the male is also influenced—as in many other animals—by memories of his previous sexual experiences, particularly the unsuccessful ones ( Griffith and Ejima, 2009). A male that decides to court then engages in an elaborate behavioral ritual to entice a female, most notably in the performance of a courtship song. Produced by the vibration of one wing, this serenade is composed of two motifs: sine song and pulse song. The latter is important for a female to Epigenetics inhibitor determine whether her suitor is of the same species ( Murthy, 2010). Male courtship behavior—and the decision to initiate it—is controlled in large part by about 2000 neurons that express the sex-specific Selleck JQ1 transcription factor FruitlessM (“FruM neurons”) (Dickson, 2008 and Manoli et al., 2006). These neurons encompass sensory cells that detect pheromones, interneurons in higher brain centers, and motor neurons, including those in

the ventral nerve cord (VNC) in the thorax that control song production (Cachero et al., 2010, Kimura et al., 2008 and Yu et al., 2010). Inhibition of all FruM neurons prevents courtship in males, indicating their necessity for this behavior (Dickson, 2008 and Manoli et al., 2006). Conversely, optogenetic activation of FruM neurons in the VNC in decapitated males is sufficient to induce singing, suggesting however that these thoracic FruM neurons function as regulators or integral components of the central pattern generator for song (Clyne and Miesenböck, 2008). Surprisingly, beheaded females can also be induced to sing—albeit slightly out of tune—when equivalent VNC neurons are activated (Clyne and Miesenböck, 2008). Given the presence of a latent song generator

in both sexes that is normally activated only in males exposed to female pheromones, which neurons in the brain make the decision to sing? The groups of Barry Dickson (von Philipsborn et al., 2011) and Daisuke Yamamoto (Kohatsu et al., 2011) addressed this question by modifying the gain-of-neural-function approach established previously (Clyne and Miesenböck, 2008). Using complementary intersectional and clonal expression strategies, both teams expressed the heat-sensitive ion channel, TrpA1, in small, distinct subsets of FruM neurons in hundreds of different flies. They then screened these animals to identify those in which heat-induced depolarization of the TrpA1-expressing neurons was sufficient to induce males to sing in the absence of females.

The resistance of the patch pipettes was 4–6 MΩ when filled with an intracellular solution consisting of 150 mM Cs-gluconate, 10 mM HEPES (pH 7.3), 8 mM MgCl2, 2 mM Na2ATP, 0.5 mM Na2GTP, 0.2 mM EGTA, and 5 mM N-ethyl bromide quaternary salt

(QX-314) (290 mOsm/kg). For the experiments shown in Figures 7B and 7C, synthetic peptide, pep-S645A, or pep-S645E (300 μM each) was added to the patch pipette see more solution to be perfused postsynaptically. The solution used for slice storage and recording consisted of 125 mM NaCl, 2.5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 1.25 mM NaH2PO4, 26 mM NaHCO3, and 10 mM d-glucose, which was bubbled continuously with a mixture of 95% O2 and 5% CO2. Picrotoxin (100 μM; Sigma) was always included in the assay to block inhibitory synaptic transmission. Veliparib To evoke EPSCs, we stimulated the Schaffer collaterals with a glass stimulating

electrode placed on the stratum radiatum of the CA1 region (200–300 μm from the recorded neurons). The stimulus intensity was subsequently adjusted to 50% of the maximal EPSC amplitude. For LTD experiments, EPSCs were recorded successively from CA1 neurons voltage clamped at –80mV at a frequency of 0.1 Hz. After stable EPSCs were observed for least 10 min, LFS (1 Hz, 300 stimuli at –40mV) was applied. Access resistances were monitored every 10 s by applying hyperpolarizing steps (2mV, new 50 ms) throughout the experiments; the measurements were discarded if the resistance changed by more than 20% of its original value. The current responses were recorded using an Axopatch 200B amplifier (Molecular Devices), and the pCLAMP system (version 9.2; Molecular Devices) was used for data acquisition and analysis. The signals were filtered at 1 kHz and digitized at 4 kHz. We thank J. Miyazaki (Osaka University), K. Nakayama (Kyoto University), M.A. Frohman (Stony Brook University), and J.G. Donaldson (National Institutes of Health) for providing the pCAGGS

expression vector, human β2 adaptin cDNA, pVenus (1–173) N-1 and pVenus (155–238) C-1 vectors, and the anti-ARF6 antibody, respectively, and S. Narumi for technical assistance. This work was supported by Ministry of Education, Culture, Sports, Science, and Technology (MEXT) and/or Japan Society for the Promotion of Science, Grant in Aid for Scientific Research to Y.K. (20247010), S.M. (22700343), W.K. (23240053), and M.Y. (23689012), by Core Research for Evolutional Science and Technology to M.Y., and by Special Coordination Funds for Promoting Science and Technology to H.H. from MEXT and the Mitsubishi Research Foundation. “
“The cerebellar cortex plays a crucial role in orchestrating the coordination and timing of body movements (Mauk et al., 2000), and cerebellar deficits or damage typically results in severe ataxia (Grüsser-Cornehls and Bäurle, 2001).

The above results indicate that neurons near the microprism face (100–300 μm away) survived prism insertion and maintained their structural integrity for months. In addition, histological evaluation with staining for hematoxylin NVP-BKM120 datasheet and eosin (H&E) (Figures 1E and 1G), Nissl (Figure 1C), and DAPI (data not shown) indicated that the imaged regions were comparable to more distant brain tissue (400–500 μm away) and to neurons from nonimplanted mice (not shown). Small but significant increases in cell density were observed within the first 50 μm from the prism face (p < 0.05, n = 7 samples from 5 mice), followed by small

but significant decreases at 50–100 μm and 100–150 μm away (p < 0.05) and a return to normal density beyond 150 μm from the prism (Figure 1G, all p > 0.05). Staining for astrocytes (anti-GFAP) and microglia (anti-CD11b), indicators of brain trauma, did not show evidence of chronic Paclitaxel tissue scarring at 27 days after surgery (Figure 1F). These data are consistent with studies showing a persistent macrophage response <50 μm from chronically implanted electrodes with decreased neuronal density at 0–150 μm from the

electrode (Biran et al., 2005). These data are also consistent with our previous studies using acute microprism implants, in which propidium iodide staining demonstrated that neuronal Calpain damage was limited to <150 μm from the prism face (Chia and Levene, 2009b). Nevertheless, a key question is whether the prism implant causes spreading depression, silencing, or other major changes in activity of local cortical neurons at distances >150 μm from the microprism face. We confirmed the sustained presence of generally normal spontaneous activity at distances of ∼100–200 μm from a chronically implanted prism using multi-unit recordings of endogenous and stimulus-evoked activity in cortical layer 5 using repeated

penetrations with tungsten microelectrodes in ketamine/xylazine anesthetized mice (see Figure S2A; Supplemental Experimental Procedures; n = 3 animals). Neurons showed similar characteristic fluctuations between Up and Down states of spontaneous activity (e.g., Ros et al., 2009), before prism implantation, as little as 10 min after prism implantation, as well as 3 days and 120 days after implantation (Figures S2B–S2E). Multiunit responses to air-puff stimulation of facial vibrissae revealed that tactile sensory inputs to neurons near the prism face also remained largely intact, demonstrating localized and spatially specific responses with similar response latency (∼15–20 ms following air-puff onset) and dynamics between recordings prior to and immediately following implantation (Figures S2F and S2G).

This pattern would follow the precedent set by neurexins for widely expressed presynaptic regulators interacting with structurally unrelated postsynaptic ligands at different types of synapses ( Williams et al., 2010). Understanding how the brain assembles specific types of synapses between

the correct partner cells will require consideration of multiple parallel trans-synaptic signaling complexes, and the latrophilin-FLRT Crizotinib complex is poised to be an important unit in accomplishing this task. Given the genetic association of LPHN3 mutations ( Arcos-Burgos et al., 2010, Arcos-Burgos et al., 2010, Domené et al., 2011, Jain et al., 2011, Martinez et al., 2011 and Ribasés et al., 2011) and FLRT3 copy number variations ( Lionel et al., 2011) with ADHD, further characterization of the FLRT3-LPHN3 complex may lead to a better understanding of the pathology and etiology of this disorder. Please CP-868596 solubility dmso see the Supplemental Experimental Procedures. We thank Katie Tiglio, Joseph Antonios, Christine Wu, and Tim Young for assistance with virus injections, virus and recombinant protein production, and antibody testing. This work was supported by the Brain and Behavior Research

Foundation (formerly NARSAD) (J.d.W.), Autism Speaks grant 2617 (D.C.), NIH fellowship F32AG039127 (J.N.S.), and NIH grants NS067216 (A.G.), NS064124 (A.G.), P41 RR011823 (J.R.Y.), and R01 MH067880 (J.R.Y.). “
“A hallmark of the mammalian neocortex is the arrangement of

functionally distinct neurons in six horizontal layers, which possess distinct properties in different sensory or motor areas (Leone et al., 2008 and Molyneaux et al., 2007). The importance of this arrangement is revealed when it is disturbed, such as in patients with brain malformations, which are largely Tolmetin composed of neuronal dysplasia in the cerebral cortex (Bielas et al., 2004, Guerrini and Parrini, 2010 and Ross and Walsh, 2001). One group of malformations, periventricular heterotopia (PH), results in cortical gray matter (GM) of varying size located at the ventricular margin. These defects can be associated with epilepsy and mental retardation (Guerrini and Parrini, 2010). While PH is clinically heterogeneous and also exhibits locus heterogeneity, most of the X-linked cases are due to mutations in a gene encoding the F-actin binding phosphoprotein Filamin A (Guerrini and Parrini, 2010 and Robertson, 2004). A second group of neuronal migration disorders consists of mutations in genes encoding microtubule (MT)-associated proteins, like Doublecortin (DCX) and Lissencephaly-1 (LIS1), resulting in partial or incomplete migration of neurons to their cortical locations during development (Bielas et al., 2004 and Ross and Walsh, 2001).

The findings do not show a simple one-to-one equivalence across species and techniques, but analogous signals conveying the same information are extensively GDC-0068 nmr present. Thus, in monkeys and humans, both the hippocampus and entorhinal cortex provide similar learning- and memory-related neural signals during tasks of new association learning. We report that in monkeys and humans both the hippocampus and entorhinal cortex signal the very first time a novel

stimulus is presented with a differential BOLD fMRI or LFP signal relative to subsequent presentations of that stimulus, although the polarity of the signal differed across species. These findings are consistent with previous findings in the human literature (Law et al., 2005 and Tulving et al., 1996), and with single unit studies in the rodent hippocampus (Cheng and Frank, 2008 and Fyhn et al., 2002), although to our knowledge have not been reported before in the monkey entorhinal cortex or hippocampus. The signals previously reported in humans have commonly been linked to memory encoding strength and may provide an initial measure of how well that stimulus or event may be remembered. These findings suggest that the hippocampal novelty effects are highly conserved across species. this website We also show that the monkey and

human hippocampus and entorhinal cortex differentiate between novel stimuli seen for the first time during that recording session and highly familiar stimuli seen daily for many months with increased

LFP and BOLD fMRI responses, respectively to the familiar stimuli. A similar differential familiarity signal has also been reported in the perirhinal cortex at the level of single unit responses, although the latter responses are opposite in polarity with enhanced responses to novel relative to familiar stimuli (Fahy et al., 1993, Li et al., 1993 and Xiang and Brown, 1998). Enhanced single unit activity to familiar stimuli relative to novel stimuli has been described in the macaque prefrontal cortex (Xiang and Brown, 2004) and was interpreted as playing a role in the process of long-term memory retrieval. Another common familiarity signal seen at the single unit level of analysis is a decremental response as initially novel very stimuli are repeated. Early studies in monkeys reported no such decremental signal in the hippocampus relative to the perirhinal cortex (Brown and Aggleton, 2001, Li et al., 1993, Riches et al., 1991 and Zhu et al., 1995). However, more recently, several studies have described such decremental signals in the monkey (Jutras and Buffalo, 2010 and Yanike et al., 2009) or human (Pedreira et al., 2010) hippocampus. These findings suggest that the monkey and human hippocampus and entorhinal cortex exhibit a wider range of familiarity signals than previously appreciated and support the much debated view in the literature that the hippocampus not only contributes to recollection (Brown and Aggleton, 2001 and Eichenbaum et al.

Participants viewed a clock arm that made a p53 inhibitor clockwise revolution over 5 s and were instructed to stop the arm to win points by a button-press response (Figure 1A). Responses stopped the clock and displayed the number of points won. Payoffs on each trial were determined by response time (RT) and the reward function of the current condition. The use of RT also provides a mechanism to detect exploratory responses in the direction of greater uncertainty, because they can involve a quantitative change in the direction expected without requiring participants to completely

abandon the exploited option (e.g., in some trials the exploration component might predict a shift from fast to slower responses, and participants might indeed HKI-272 solubility dmso slow down but still select a response that is relatively fast). As already noted, learning was divided into blocks within which the reward function was constant. However, the reward functions varied across blocks, and at the outset of each block participants were instructed that the reward function could change from the prior block. Across blocks, we used four reward functions in which the expected value (EV; probability × magnitude) increased (IEV), decreased (DEV), or remained constant (CEV, CEVR) as RT increased (Frank et al., 2009 and Moustafa

et al., 2008) (Figures 1B–1D). Thus, in the IEV condition, reward is maximized by responding at the end of the clock rotation, while in DEV early responses produce better outcomes. In CEV, reward probability decreases and magnitude increases over time, retaining a constant EV over each trial that is nevertheless sensitive to subject preferences for reward frequency and magnitude. CEVR (i.e., CEV Reversed) is identical to CEV except probability and magnitude move in opposite directions over time. Over the course of the experiment, participants completed two blocks of 50 trials for each reward function, with

block order counterbalanced across participants. While not explicitly informed of the different conditions, the box around the clock changed its color at the start of PAK6 each 50 trial run, signifying to the participant that the expected values had changed. Note that even though each reward function was repeated once, a different color was used for each presentation and participants were told at the beginning of a block that a new reward function was being used. Within each block, trials were separated by jittered fixation null events (0–8 s). The duration and order of the null events were determined by optimizing the efficiency of the design matrix so as to permit estimation of event-related hemodynamic response (Dale, 1999). There were eight runs and 50 trials within each run. Each run consisted of only one condition (e.g., CEV) so that participants could learn the reward structure.

11 were among the first to report a greater prevalence of functional limitations, including reduced mobility, among older female cancer survivors (<5 years post-diagnosis) compared to older women with no cancer history. Cancer

survivors were more likely to report that they were unable to do heavy household work (odds ratio (OR) = 1.47, 95%CI: 1.27, 1.69), walk one-half mile (OR = 1.31, 95%CI: 1.1, 1.54), or walk up and down stairs (OR = 1.34, 95%CI: 1.05, 1.72). Functional limitations may begin a cascade to disability, dependence, and death.12 In fact, slower 20-m walk speeds are associated with higher mortality (OR = 1.09, 95%CI: 1.02, 1.16) and faster progression to disability (OR = 1.25, 95%CI: 1.13, 1.35) among older cancer survivors.13 Cancer treatment BMS-354825 in vitro can alter physical functioning in ways that are similar to aging (i.e., weakness) but also in ways unique to treatment. Chemotherapy is associated with sarcopenia,14, 15, 16, 17 and 18 fatigue,19 and deconditioning.20 Regimens that contain neurotoxic agents also cause peripheral neuropathy21 and vestibulotoxicity22 and 23 that affect balance and mobility. Neuropathy and vestibulotoxicity in older adults are associated with poor balance, low mobility, and subsequent falls.24, 25 and 26 The relative contributions

of muscle weakness, neuropathy, and vestibular dysfunction to physical functioning in cancer survivors are not yet known, but approaches that strengthen muscles used in everyday movements Torin 1 ic50 and strengthen the damaged sensory systems

that contribute to instability during movement could be the best rehabilitation strategy for reversing functional declines caused by neurotoxic cancer treatment. Falls and disability share common risk factors (e.g., weakness, instability, and altered gait) that typically increase with age; and, like disability, falls are a significant concern for cancer survivors. Chen et al.27 reported an elevated risk of falls after women developed breast cancer compared to women never diagnosed with cancer (hazard ratio (HR) = 1.15, 95%CI: 1.06, 1.25), and others have observed fall rates in cancer survivors that are double those of cancer-free peers28 or community-dwelling about older adults.29 Cancer treatment itself and inactivity that often accompanies treatment can worsen age-related weakening. For cancer survivors treated with chemotherapies that are toxic to the nervous system, neuropathy and vestibular dysfunction (e.g., damage to the inner ear) are common side effects. In a single report of patients who received neurotoxic chemotherapies (n = 109), 20% experienced a fall during treatment and fallers had higher scores on self-report measures of neuropathy than non-fallers. 30 Using posturography tests that evaluate sensory inputs to balance control, breast cancer survivors with a history of falls have worse performance in conditions challenging vestibular input to balance control compared to survivors with no fall history.