It is postulated that with longer exposure to the short-leg walking boots, motor control would be optimized and internal loading would be minimized in response to the added structural stability selleck chemicals provided

by the walking boots. However, the long term neuromuscular adaptations to short-leg walking boots have not been directly investigated. In conclusion, short-leg walking boots are associated with adaptations in neuromuscular activation patterns of the extrinsic ankle musculature. Specifically, an earlier onset and longer durations of muscle activation are key acute responses to short-leg walking boots. However, the intensity of muscle activation was not reduced in the current study. These alterations in muscle activation patterns may limit the efficacy of the short-leg walking boots. Future research is warranted to examine long term neuromuscular adaptations to short-leg walking boots and to the biomechanical responses to imposed leg length discrepancies associated with short-leg walking boots. This study was funded in part by a grant from DeRoyal Industries, Inc., Powell, TN, USA. “
“An increasingly serious health challenge in U.S. schools is child obesity resulting from unhealthy eating and insufficient physical activity. Compared with their counterparts from 1976 to 1980, current American children and adolescents’ overweight prevalence increased three folds, from 6.5% to 17.0% for the 6–11 year age group and from 5.0% to 17.6%

for the 12–19 year age group.1 It is a consensus that one cause of the child obesity epidemic is the caloric imbalanced living behavior, children simply taking in more calories than burning them Compound Library supplier out.2, 3 and 4 One way to increase children’s caloric expenditure is to increase their physical activity during physical education. It is recommended that schools offer a weekly minimum of 150 min physical education and structure physical education lessons as such that children are

physically active most of the time.5 and 6 Therefore, empirical evidence is needed to help school administrators most and physical/health educators to schedule and structure lessons to increase caloric expenditure in physical education. Lesson factor variables such as content type and lesson length and personal factors such as body mass index (BMI), gender, and age can influence children physical activity participation and, consequently, their caloric expenditure.7 For example studies on gender, a personal level variable, reported that boys tend to be more physically active than girls during school day8 and in physical education.9 For lesson factors, outdoor lessons seem to induce more physical activity than indoor lessons and children are likely to spend more calories in fitness and sport skill development lessons than in game or free play lessons.10 Conceptually, these factors can be viewed in a two-level structure: personal characteristics and lesson factors. In research, these factors usually are examined separately.

We implanted a small piece of ethylene-vinyl acetate PI3K inhibitor copolymer (Elvax) containing 3-MP or vehicle on the surface of the cerebellar vermis (lobules 6–8) at P10 as described previously (Kakizawa et al., 2000, Kakizawa et al., 2003 and Kakizawa

et al., 2005). When CF innervation was tested within the lobules 6–8 at P23–P40, 80% of PCs (45/56) in vehicle-treated mice were innervated by single CFs (Figure 4D). By marked contrast, 48% of PCs (30/62) from 3-MP-treated mice were multiply-innervated by two or three CFs (Figure 4D) with significant difference in the frequency distribution (p = 0.002) (Figure 4D). Basic synaptic properties of CF-EPSCs were identical between the 3-MP- and vehicle-treated mice (Table S2). These results indicate that suppression of GAD activity in the cerebellum starting at P10 effectively perturbs CF synapse elimination presumably by weakening GABAergic transmission. Next, we studied whether there is a critical selleck kinase inhibitor period for the GAD-sensitive CF synapse elimination. We implanted Elvax containing 3-MP or vehicle to the cerebellar lobules 6–8 at P17. As shown in Figure 4E, the frequency distribution histograms were similar between the vehicle- and 3-MP-treated mice (p = 0.725). No difference was observed in CF-EPSC kinetics or

paired-pulse ratio between the two experimental groups (Table S2). These results suggest that the critical period for the GAD-sensitive CF synapse elimination is around P10 to P16. 3-MP inhibits not only

GAD67 but also the other GAD isoform GAD65, and both were expressed in the mouse cerebellum during the second postnatal week (Figures S4A–S4L). To test the contribution of GAD65 to CF-synapse elimination, we analyzed GAD65 knockout (GAD65 KO) mice (Asada et al., 1996). GAD65 KO mice have been reported to maintain normal levels of GAD67 and GABA in the brain (Asada et al., 1996). We found both the amplitude and frequency of mIPSCs were normal in GAD65 KO PCs (Figures S4M–S4O). In mature stage, there was no significant difference between wild-type and GAD65 KO mice in terms of the number of CFs innervating each PC (p = 0.406) (Figure S4P), indicating that 17-DMAG (Alvespimycin) HCl CF synapse elimination is normal in GAD65 KO mice. These data indicate that the effects of 3-MP on mIPSCs and CF synapse elimination are attributable to the inhibition of GAD67. Next, we examined whether pharmacological enhancement of GABAergic inhibition by diazepam, a benzodiazepine-site agonist, facilitates CF synapse elimination in GAD67+/GFP mice. We assayed the effects of diazepam on mIPSCs in cerebellar slices from GAD67+/GFP mice at P10–P14 (Figures 5A–5C). Diazepam significantly enhanced the amplitude of mIPSCs which returned to the control level by subsequent application of flumazenil, a benzodiazepine-site antagonist (Ctrl: 66 ± 2.3 pA; DZ: 88 ± 3.3 pA; DZ+Flu: 62 ± 2.1 pA, n = 8; p < 0.001, Ctrl versus DZ; p = 0.

(P34) Being unwell: Fifteen individuals identified specific health problems that had prevented them from completing the program. The most commonly identified health problem, reported by nine participants, was pain in the legs or spine. This pain arose from a number of different causes and participants generally associated it with pre-existing conditions: Yes, it’s painful because the blood ABT-737 cell line clot is there; I have a blockage in my vein, I refuse the operation because I

am too old for operation. (P33) Two participants reported episodes of new pain (sprained ankle and acute back pain), the onset of which they attributed to activities undertaken in caring for others: I was looking after my grandchildren and it’s quite possible that I picked my grandson up the wrong way. (P34) Six participants identified other non-respiratory problems that contributed to their inability to complete the program: Well sometimes it is because my thyroid doesn’t work so I get very tired. And

I also have diverticulitis which doesn’t help sometimes. (P37) Four participants reported that an exacerbation of COPD prevented their completing pulmonary learn more rehabilitation: Because my chest was very bad we sort of put it off for a month and then I just never got around to going back again. (P22). Getting there: Six participants indicated that travelling to the pulmonary rehabilitation venue prevented their ongoing attendance. Multiple barriers were discussed within this theme, including a lack of transport options, inconvenient timing of transport, poor mobility, and cost: Well, I don’t have a car myself, and as you know I can’t get onto public transport because my legs just won’t let me. I’ve got a walker now. I’ve got to rely on taxis and that gets a bit expensive. (P28) Five participants indicated that they would only be able to complete pulmonary rehabilitation if they could undertake the program in their own home. For some participants this was to

avoid the burden of travel, whereas for others it was because they felt more secure in their own environment: Yes, (if) that program (could be secondly at) my place it can be help, but not in the hospital. (P33) Four participants indicated that the program was too early in the day, whilst one participant who had returned to work indicated that he would be more likely to complete the program if it were to run outside of working hours. Four participants indicated that they felt too tired to complete the program, either due to general fatigue or because the exercise program increased their feelings of fatigue. Four participants indicated that they didn’t feel any benefit from attending the program. These participants had attended between one and four sessions before withdrawing. Three participants indicated that living alone and a lack of supportive family or friends had contributed to their failure to complete the program.

While both are essential components of the control system, the EVC theory ascribes to dACC a role in specification but not regulation, as we discuss below. Monitoring. In order to specify the appropriate control signal and deploy regulative functions in an adaptive manner, the system must have access to information about current

circumstances and how well it is serving task demands. Detecting and evaluating these requires a monitoring mechanism. The conflict-detection component in the Stroop model provides one example of such a monitoring function and how it can guide specification: the occurrence of response conflict indicates that insufficient control is being allocated to the current task (see Botvinick, 2007, Botvinick et al., 2001 and Botvinick et al., PI3K inhibitor 2004). Selleckchem ZD1839 In this instance, conflict indicates the need to re-specify control signal intensity. However, conflict is just one among many signals that can indicate the need to adjust intensity. Others include response delays, errors, negative feedback, and the sensation of pain. These signals all carry information about performance within

a task and how to specify control signal intensity. Monitoring must also consider information relevant to the specification of control signal identity; that is, to task choice. Such information can come from external sources (e.g., explicit instructions, cues indicating new opportunities for reward, or the sudden appearance of a threat) or internal ones (e.g., diminishing payoffs from the current task indicating

it is no longer worth performing, recollection of another task that needs to be performed, etc.). In all of these cases, monitoring must be responsive to, but should be distinguished Adenylyl cyclase from, the sensory and valuative processes that represent the actual information relevant to specification. Thus, just as we distinguish between specification and regulation on the efferent side of control, we distinguish between monitoring and valuation on the afferent side. In each case, the EVC theory ascribes to dACC a role in the former, but not the latter. Early research on control focused on regulative and monitoring mechanisms, but growing attention is being paid to the problem of control-signal specification. Work in this area has been driven increasingly by ideas from research on reward-based decision making and reinforcement learning. One emerging trend has involved reframing control-signal specification as an optimization problem, shaped by learning or planning mechanisms that serve to maximize long-term expected reward (Bogacz et al., 2006, Dayan, 2012, Hazy et al., 2007, O’Reilly and Frank, 2006, Todd et al., 2008 and Yu et al., 2009). Under this view, cognitive control can be defined as the set of mechanisms responsible for configuring behavior in order to maximize the attainment of reward.

Some of these molecules may be expressed as opposing gradients or in a region-specific manner before and/or independently, since dilation of input does not prevent formation of at least some basic region-specific cytoarchitectonic

features (Figure 1C; Arimatsu et al., 1992, Cohen-Tannoudji et al., RG7204 1994, Grove and Fukuchi-Shimogori, 2003, Miyashita-Lin et al., 1999, O’Leary and Borngasser, 2006, Rakic et al., 1991 and Rubenstein and Rakic, 1999). An instructive example of how new regions could emerge via differential expansion of the cortical surface is the demonstration that frontal cortex can be enlarged in surface area without change in the size of other areas via manipulation of the transcription factors Fgf8, Fgh17, and Emx2 (Cholfin and Rubenstein, 2008). Opposing molecular gradients during development can, at some points of their intersection, provide instructions and coordinates for the creation of the

new neocortical areas (Figure 1C). For example, prospective Broca and Wernicke areas, which are formed as islands in the frontal and temporal lobes display a distinct temporarily enriched gene expression pattern that is distinct from the mice or macaque cerebrum at the comparable prenatal stages (e.g. Abrahams et al., 2007, Johnson et al., 2009 and Pletikos et al., 2013; Figure 2). The complex process of radial glia-guided neuronal Volasertib purchase migration of projection neurons was probably introduced during evolution to enable translation of the protomap at the VZ to the overlying cerebral cortex and preservation of neuronal positional information (Rakic, (-)-p-Bromotetramisole Oxalate 1988). The cellular and molecular mechanisms underlying this complex event involve cooperation of multiple genes and molecules including astrotactin, doublecortin, glial growth factor, erbB, Reelin, Notch, NJPA1, Integrins, Sparc-like1, Ephs, MEKK4, various calcium channels, receptors, and many others (e.g., Anton et al., 1999, Gleeson and Walsh, 2000, Hatten, 2002, Gongidi et al., 2004, Hashimoto-Torii et al., 2008,

Hatten, 2002, Komuro and Rakic, 1998, Nadarajah and Parnavelas, 2002, Reiner et al., 1993, Sarkisian et al., 2006 and Torii et al., 2009). Radial migration is particularly elaborate in the convoluted primate cerebrum, requiring modification of the radial glia (Rakic, 2003). This process is extremely relevant to human cerebral function, as neuronal migrational abnormalities are a major cause of human neurodevelopmental conditions (Gleeson and Walsh, 2000 and Lewis and Levitt, 2002). Yet mutations that cause severe abnormalities in human brain may cause far more subtle phenotypes in mouse, consistent with the exigencies of much longer migration in humans (e.g., Gleeson and Walsh, 2000 and Lewis and Levitt, 2002). There are also several examples of new types of neurons in the human cerebrum, including von Economo neurons, which are also observed in the brains of other large mammals and yet still may play an important role in human cerebral cortex (Butti et al., 2013).

, 1999) and robust changes in eCB and NO levels in the hypothalamus (Di Marzo et al., 2001, Kirkham et al., 2002 and Squadrito et al., 1994). While we investigate GABA signaling in the DMH following

food deprivation, other studies have reported an increase in neuronal activity in the DMH, as assessed by changes in Fos expression, in response to refeeding following food deprivation (Johnstone et al., 2006 and Renner et al., 2010). Our finding that food deprivation produces an increase in GABA drive to DMH neurons is in agreement with these studies and suggests that enhanced inhibition of these neurons is a mechanism to cope with the lack of food. These neurons are then activated upon refeeding following a period of food

deprivation. Although we report LTPGABA of evoked synaptic GW-572016 mw responses this website following HFS in food-deprived animals, this is accompanied by a small decrease in the amplitude of spontaneous IPSCs. Under these conditions, in which CB1Rs are compromised, we surmise that HFS will still produce eCBs, but they have no presynaptic binding partner available. Thus, the eCBs may preferentially bind to postsynaptic TRPV channels and promote a postsynaptic LTDGABA. This putative postsynaptic LTD may rely on a mechanism similar to that reported at glutamate synapses in other brain regions (Chávez et al., 2010 and Grueter et al., 2010) and may explain why we observe a slight depression following HFS when both the CB1R and NO signaling pathways are blocked. Food deprivation is one of the most fundamental stressors to an organism, with elevated CORT levels observed within just 4 hr following removal of food from young rats (Dallman et al., 1999). In this study, we demonstrate that CORT, through actions at genomic glucocorticoid receptors, is essential for shifting the plasticity from LTDGABA to LTPGABA in the DMH following acute food deprivation. Accumulating evidence suggests that CORT can interfere with CB1R expression and signaling. In the PVN, we have recently reported a downregulation

of CB1Rs following repeated stress that is mediated by activation of genomic the glucocorticoid receptors (Wamsteeker et al., 2010). Prolonged CORT treatment also decreases the density of CB1Rs in the hippocampus (Hill et al., 2008) and impairs CB1R-mediated control of GABA transmission in the striatum (Rossi et al., 2008). Importantly, it appears that the increase in CORT must be robust and prolonged because challenges that cause either prolonged but small changes in CORT (social isolation) or robust but transient increases (30 min immobilization) failed to shift the balance of plasticity toward LTP. It is important to note that CORT can also induce eCB biosynthesis and release (Di et al., 2003, Hill et al., 2005 and Malcher-Lopes et al., 2006), and that elevated levels of eCBs can result in desensitization and synaptic exclusion of CB1Rs (Mikasova et al., 2008).

The Ca2+ dependence, together with the fact that moderately depolarizing the

cells with increased extracellular K+ concentration did not significantly affect the accumulation of LTR in synaptic vesicles (Figure 1), argues against a passive LTR release resulting from the disruption of the electrical gradient across the synaptic membrane. Moreover, the different amounts of dye that were lost in response to varying stimulation intensities fit INCB024360 the expectations of vesicular exocytosis (Figure 3C). Importantly, intense LTR signals that did not colocalize with the synapse marker synaptotagmin1 and might stain lysosomes or other acidic cellular organelles did not show a decrease in fluorescence upon electrical stimulation (Figure 3D), again arguing for the release of LTR from synaptic vesicles via Ca2+-dependent exocytosis. To assess APD release after chronic treatment in vivo, we performed microdialysis in freely moving rats, which was followed by quantification of neurotransmitter and HAL. Animals were implanted with osmotic minipumps, which delivered HAL (0.5 mg/kg/d) for 14 days (Samaha et al., 2007), a dose that was shown to provide a brain

DA D2 receptor occupancy similar to that required for Sirolimus ic50 human antipsychotic treatment action (Kapur et al., 2003). On day 14, triple-probe microdialysis was performed, measuring extracellular levels of HAL in the prefrontal cortex (PFC) and the dorsal striatum (DStr) and extracellular levels of DA and serotonin (5-HT) in the nucleus accumbens (NAc), as a reference for transmitter release (Figure 3E) (Amato et al., 2011). Baseline levels of HAL were 143.9 + 28.4 pg/ml in the PFC all and 179.1 + 40.5 pg/ml in the DStr (n = 5), which was not corrected for recovery (in vitro, 84.7%). A 100 mM K+ challenge, applied locally by reverse dialysis (Chen and Kandasamy, 1996), significantly increased the extracellular HAL concentrations compared to the baseline in the PFC (40 min samples,

samples S3 and S4 versus baseline; p < 0.05) and DStr (40 min samples, samples S3 and S4, versus baseline; p < 0.05) during the K+ challenge (Figure 3F). This was paralleled by an increase in extracellular DA (20 min samples, samples S5–S8, versus baseline; p < 0.05) and 5-HT levels (20 min samples, samples S5 and S6, versus baseline; p < 0.05) (Figure 3G). These data suggest that the extracellular HAL concentration in the brain is activity dependent after chronic HAL treatment in freely moving animals. It behaves similarly to the neurotransmitters DA and 5-HT. The different amounts of secreted HAL might reflect varying accumulation, release, or even receptor distribution properties, depending on the brain region. The activity-dependent increase of HAL concentrations in the dialysate from the synaptic cleft supports the idea of transient high APD concentrations, especially in close proximity to the vesicle fusion sites after synaptic vesicle fusion and APD release.

Reactivation of hippocampal ensemble firing occurs preferentially during CA1 sharp wave-ripples (O’Neill et al., 2010), which are in turn temporally correlated with thalamocortical sleep spindles (Siapas and Wilson, 1998; Sirota et al., 2003; Mölle et al., 2006); spindles themselves are phase locked to slow-waves and also associated with ensemble reactivation (Johnson et al., 2010). These temporal interrelationships may orchestrate

the induction of synaptic plasticity during sleep by aligning replay of ensemble activity during ripples and spindles with periods of high cortical excitability during slow-wave “up states” (Diekelmann Akt inhibitor ic50 and Born, 2010). However, circuit mechanisms of ripple-spindle coordination and their dependence on global sleep architecture have not been directly demonstrated. Given the interdependencies between neural activity during sleep and waking behavior, it is clear that sleep disruption may cause and/or exacerbate cognitive symptoms in diseases including schizophrenia,

depression, Parkinson’s, Alzheimer’s, and Huntington’s disease (Wulff et al., 2010). In particular, schizophrenia-associated deficits in attention and memory processing may be Olaparib nmr attributed to aberrant sleep-related consolidation mechanisms (Manoach and Stickgold, 2009) and therefore be reflected by altered neural activity during sleep. Reductions in the number and power of slow-waves (Keshavan et al., 1998; Göder et al., 2006) and reductions in sleep spindle density (Ferrarelli et al., 2010; Manoach et al., 2010; Keshavan et al., 2011) correlate with either baseline cognitive deficits (Göder et al., 2006) or deficits in overnight memory

recall (Göder et al., 2008; Manoach et al., 2010; Wamsley et al., 2012) in schizophrenia. These sleep abnormalities therefore constitute important targets for novel therapeutic intervention. The MAM-E17 rat neurodevelopmental model of schizophrenia (Moore et al., 2006) employs administration of a mitotoxin MAM (methylazoxymethanol-acetate) to pregnant rats to induce a neurodevelopmental disruption, selectively targeting limbic-cortical circuits by timing embryonic day 17 MAM injections Cediranib (AZD2171) to coincide with hippocampal and prefrontal cortical embryogenesis (Lodge and Grace, 2009). Although no single intervention can model all aspects of schizophrenia in a rodent, the MAM-E17 model is therefore particularly useful in studying limbic-cortical dysfunction in neurodevelopmental disorders. MAM-E17 exposed rats show cognitive changes reminiscent of those seen in schizophrenia, including impairments in spatial working memory (Gourevitch et al., 2004), attentional set-shifting (Featherstone et al., 2007), and reversal learning (Moore et al., 2006). MAM-E17 exposed rats also harbor glutamatergic dysfunction (Hradetzky et al.

e., minimized their anticipated guilt) to

trials in which they returned less than they believed their partner expected (i.e., enhanced their financial reward). The duration of the decision phase was modeled as the time to decision. There was no significant difference in the response time between trials in which participants matched expectations (mean = 3412.29 ms, sd = 1310.65) as compared to trials in which they returned less than their expectation (mean = 3666.87 ms, sd = 1475.47; b = 0.25, se = 0.14, t = 1.80, p = 0.08). It is important to note that this response XAV-939 solubility dmso time is not particularly meaningful as participants were required to scroll through their choices and the starting point was random (see Experimental Procedures). The contrast, illustrated in Figure 4, revealed increased activity in the insula, supplementary motor area (SMA), dorsal

anterior cingulate (DACC), dorsolateral prefrontal cortex (DLPFC), and parietal areas, including the temporal parietal junction (TPJ), when participants matched their second-order beliefs about their partner’s expectations, thus minimizing guilt. Returning less than their second-order belief, and thereby increasing financial gain, was associated with greater activity in the ventromedial prefrontal cortex VMPFC, bilateral nucleus accumbens (NAcc), and dorsomedial prefrontal cortex (DMFPC) (See Table S2 for all identified regions). While the main contrast illustrates regions associated with minimizing expected guilt as compared to maximizing financial payoff, an Selleck Obeticholic Acid additional question of interest is whether these activations change parametrically as a function of the actual deviation from matching expectations. To address this question we tested a parametric contrast that compared trials in which participants matched expectations to linear deviations from MTMR9 expectations (in 10% increments). Similar to the main contrast, matching expectations

was associated with increased activity in the right insula, right DLPFC, SMA, ACC, and precuneous (see Figure 5 and Table S3). Returning incrementally less than expectations was associated with increased activity in the bilateral NAcc and MPFC (including VMPFC, DMPFC, and ACC). However, participants systematically made slightly less money in trials in which they matched expectations (mean = $12.28, sd = 5.88) compared to trials in which they returned less than they believed the other player expected ($14.58, sd = 6.79; beta = −2.08, t = 2.53, p < 0.05). To address this potential confound and to rule out the possibility that the insula is simply tracking forgone financial payoffs rather than guilt aversion, we ran an additional analysis (see Supplemental Information) that allowed us to examine the effect of matching expectations while controlling for the amount of money that subjects return (i.e., their forgone financial payoff).

The resin-bound fractions were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and cellular GTP-Rap1 levels were analyzed by immunoblotting with anti-Rap1-GTP and anti-rap1, respectively. The band intensities were then normalized to anti-Rap1 in the input lane (defined as 1.0). In this study, 8-pCPT-2′-O-Me-cAMP-AM (BioLog Life Science Institute, Bremen, Germany) was dissolved in a vehicle solution containing 0.1% DMSO and 0.1%BSA. The sections from the CA1 stratum radiatum of the hippocampus of three male EPAC−/− at

96 days old of age and three control littermates (EPAC+/+ mice) were studied. Mice were perfused with 2% paraformaldehyde + 2% glutaraldehyde in 0.1 M phosphate buffer, then postfixed in 1% osmium tetroxide in 0.1 M cacodylate NU7441 manufacturer buffer, stained en bloc with 1% uranyl acetate in 50% ethanol, dehydrated in an ethanol series and then put in propylene oxide and embedded in epon. Thin sections were stained with lead citrate.

Golgi staining was performed on four strains of male mutant mice and their respective wild-type controls at 90 ± 5 days old of age. In PI3K inhibitor this study, FD rapid Golgi Stain kit (FD NeuroTechnologies,) was used. Briefly, brains were removed from mice and immediately immersed in solution A and B for 2 weeks at room temperature and transferred into solution C for 24 hr at 4°C, as instructed on the manufacture’s experimental methods. The brains were sliced using a Vibratome (VT1000S; Leica) at a thickness of 100 μm. Bright-field microscopy (Axio Observer; Zeiss) images were taken of CA1 pyramidal neurons (80 cell with a total of 80 cm length of dendrites per group were analyzed). Images whatever were coded and synaptic spines counted in software with Image Probes. All the spines counted were also measured for spine length and spine densities were expressed as spine/μm dendrite. Comparisons between genotypes were carried out using two-way ANOVA. Electrophysiological experiments and biochemical assays were analyzed using

the Student t test. LTP analysis was performed on 10 min blocks of data within the last 30 min of the recording. This work was supported by National Natural Science Foundation of China (Grant 81130079 YL), National Institute of Health (NIH/NINDS, R01NS5051383Y.L and NIH/NIA R01AG033282Y.L), the New Century Excellent Talents in University (NCET-10-0421, L.-Q.Z.), and the NIH/NIDCD Intramural Program (R.S.P. and Y.-X.W.). “
“There is abundant evidence demonstrating a key role for the hippocampus and MEC in landmark- and path integration-based navigation (O’Keefe and Nadel, 1978, Morris et al., 1982, Nadel, 1991, McNaughton et al., 1996, McNaughton et al., 2006, Whishaw et al., 2001a, Parron and Save, 2004 and Steffenach et al., 2005). Both areas contribute to spatial mapping, with place cells in the hippocampus firing at particular locations in the environment (O’Keefe and Dostrovsky, 1971), and grid cells in MEC providing a precise two-dimensional metric for space (Hafting et al.