Wnt3 expression alone had no clear effect on axon growth compared to control. In both the Wnt3 and GFP conditions, many Forskolin manufacturer axons (about 60%) freely grew across the COS7 cells ( Figure 6C). To test the ability of Wnt3 to antagonize the negative effects of BMP7 in this assay, we coexpressed the ligands and found that Calretinin+ axons now quite readily crossed BMP7 + Wnt3-expressing COS7

cells ( Figure 6C, p < 0.001). Thus, Wnt3 apparently has minimal, if any, stimulatory effect on axon growth in this assay unless BMP7 is present, in which case it apparently counteracts the negative effects of BMP7. To examine this interaction in vivo, we introduced BMP7 along with Wnt3 in utero. Strikingly, we observed formation of the corpus callosum when we expressed Wnt3 expression along with BMP7 ( Figure 7A). Thus, it appears that Wnt3 is able to counteract the negative

effects of BMP7 on callosal pathfinding axon outgrowth. This is consistent with the onset and spatial distribution of Wnt3 at E14.5 being a critical regulator of callosum formation by allowing the pioneer axons to cross the BMP7-expressing midline meninges. Screening Library Because the mutant cortex lost Wnt3 expression before the initial pioneer axons crossed the midline, we wondered whether adding back Wnt3 would rescue the failure of the pioneer axons crossing the midline in the mutants with excess meninges (the Msx2-Cre;Ctnnb1lox(ex3) mice). To test this, we electroporated a Wnt3-expression construct into the midline cortex of Msx2-Cre;Ctnnb1lox(ex3) mice at E13.5 and examined E17.5 embryos and found that TAG1- and L1-positive corpus callosal axons are obvious in the Wnt3-electroporated brain, but GFP-electroporated brains failed to form the midline callosal trajectories ( Figure 7B). To further address

our hypothesis that Wnt3 signaling MTMR9 antagonizes BMP7 signaling, thereby allowing the corpus callosal axons to cross the midline, we examined staining for pSMAD1/5/8 in the medial cortex of BMP7-electroporated mice either with GFP or Wnt3 coelectroporation. In mice that were electroporated with BMP7 and GFP, as expected, the level of pSMAD1/5/8 immunoreactivity was markedly increased in the BMP7-electroporated medial cortex (Figure 7C). However, when Wnt3 was coelectroporated with BMP7, and the brains were examined 3 days later, the pSMAD1/5/8/ levels were blunted and were perhaps even lower than those seen in the opposite unelectroporated hemisphere (Figure 7C). To quantify these effects, we performed western blotting for pSMAD1/5/8 and normalized the signal to antibodies for GAPDH or all forms of SMAD1. In these experiments, we found that BMP7 + eGFP-electroporated cortex had a 40% higher level of pSMAD1/5/8 compared to cortex electroporated with Wnt3 + BMP7 (Figures S5A and S5B).

, 2010; Newbolt et al., 1998; Roberts and Evans, 2006). Although

all functional P2X receptors undergo conformational changes that result in the opening of a cationic pore within milliseconds of ATP binding, some P2X receptors (notably Sorafenib P2X2, P2X4, and P2X7) also undergo additional slower conformational changes (Figure 4). Pore dilation follows several seconds of ATP activation and is characterized by increases in permeability to organic cations and several dyes (Khakh et al., 1999a; Khakh and Lester, 1999; North, 2002; Virginio et al., 1999). In other P2X receptors, notably P2X1 and P2X3, extended activation by ATP results in channel closure through desensitization. Pore dilation is of interest because Selleck Antidiabetic Compound Library it occurs over seconds, endowing P2X receptors with slow signaling capabilities and potentially providing the ability to release intracellular constituents such as ATP itself. Two mechanisms have been proposed for pore dilation (Figure 4). For P2X2, P2X4, and P2X7 receptors, pore dilation appears to involve an intrinsic conformational change in the protein itself (Chaumont and Khakh, 2008; Khadra et al., 2012; Yan et al., 2008, 2010, 2011). However, for natively expressed P2X7

channels, an accessory protein may also be required, and pannexin-1 channels may be involved in receptor pore Adenylyl cyclase dilation (Jiang et al., 2005; Pelegrin and Surprenant, 2006; Pelegrin and Surprenant, 2007; Surprenant et al., 1996) in a manner that varies with the particular splice variant being studied (Xu et al., 2012). In all cases, the dilated pore state is regulated by cellular processes and mechanisms that involve the C-terminal tail. In the case of P2X4 receptors, fast-scanning atomic force microscopy has been used to image

a slow conformational change that may underlie the phenomenon within single protein molecules (Shinozaki et al., 2009). Pore dilation may allow P2X receptors to function as intrinsic frequency detectors, by switching to the larger pore state with altered signaling upon repeated ATP activation (Khakh et al., 1999a). Recent data suggest that this particular state of P2X7 receptors may be involved in susceptibility to chronic pain (Sorge et al., 2012), raising the possibility that pore dilation of other P2X receptors in the brain may also mediate important slow responses. Further structural as well as physiological studies are needed to evaluate precisely how pore dilation and dynamic selectivity filters occur and what their functions are in vivo. P2X and nicotinic receptors undergo functional interactions (Barajas-López et al., 1998; Nakazawa, 1994; Nakazawa et al., 1991; Searl et al., 1998; Searl and Silinsky, 1998; Zhou and Galligan, 1998).

They were acclimatized

to animal house facilities for seven days and were maintained under standard condition (Temperature 25 ± 2 °C, 12-h light: 12-h dark cycle) throughout the experimentation. The animals were fed with standard pellet diet (Nutrivet life science, BVD-523 cost Pune, M.S., India) and water was supplied ad-libitum. The studies were carried out as per the CPCSEA guidelines and after approval of the Institutional Animal Ethical Committee (Ref.No.: BVDUMC/443/2012-2013). Rats were randomly selected and divided into six groups of six animals each. The inter and intra group weight difference was below 20%. Hepatotoxicity was induced in rats by orally feeding 1000 mg/kg b.w. acetaminophen suspended in water. The dose of satwa was finalized on the basis of the earlier studies carried out in the laboratory. The treatment protocol, as mentioned below, was followed: Group I: Control (n = 6); received feed and water normally for 15 days The animals were observed daily for any signs of discomfort and/or infection. After 15 days of continuous treatment, animals were fasted overnight, blood was collected by retro-orbital puncture and animals were humanely sacrificed. Liver was

excised immediately, washed in saline, weighed and stored in 10% neutral buffered formalin for histological analysis. Blood was allowed to clot at R.T. for 30 min and serum was collected after centrifugation at 2000 rpm for 15 min. Marker enzymes of liver damage (serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and alkaline phosphatase (ALP)), total bilirubin,

total Cholesterol, HDL Cholesterol, total Triglycerides were estimated NLG919 using Ketanserin commercial kits (Coral clinical system, Goa, India). LDL Cholesterol (mg/dL) was estimated by using the formula: (Total Cholesterol – HDL Cholesterol) – triglycerides/5 and VLDL Cholesterol was estimated by using the formula: Triglycerides/5. Paraffin-embedded liver tissues were cut at 4 μm and stained with hematoxylin-eosin. The slides were examined under microscope and photographed. Results are presented as Mean ± Standard Error (SE). Dunnett Multiple Comparison Test and one way Analysis of Variance (ANOVA) was done to estimate the statistical significance between groups. In the present study, comparative hepatoprotective potential of T. cordifolia, T. sinensis and Neem-guduchi Satwa were evaluated by assessing activities of serum enzymes SGOT, SGPT, ALP and total bilirubin. The animals of paracetamol treated group showed elevated levels of SGOT, SGPT, ALP and bilirubin, as compared with normal control group ( Table 1). The results of comparative hepatoprotective potential of T. cordifolia, T. sinensis and Neem-guduchi Satwa on paracetamol treated rats indicate differential activity of three different species in hepatoprotection. T. cordifolia was found to have a specific action on maintaining lipid profile. The experimental group treated with T.

For each K-means partition, the method computes

the distortion, i.e., a normalized squared distance between each observation and its closest cluster center. Since the K-means partitioning may depend upon the starting points used, the K-means algorithm is repeated a number of times with different starting conditions, and a mean distortion for each prescribed value of k is obtained. A distortion curve is then generated by plotting the mean distortion as a function of k. The distortion tends to decrease as the number of clusters is increased, and this is transformed into an increase by raising the distortion to CHIR-99021 cell line a negative power, Y. Because the distortion drops when the correct number of clusters is used, and remains roughly constant when even more clusters are employed, the transformed distortion exhibits a sudden increase, or jump, at the correct value of k. If one examines the size of the jumps in the transformed distortion, the largest jump is therefore an indication of the proper number of clusters. We also used MATLAB to perform a principal Alpelisib datasheet component analysis. We computed the principal components of the entire data set (30 properties) as well as the 15 properties that were significantly

different between the two populations. The authors would like to members of the Spruston laboratory for helpful discussions and Adam Hantman for reagents. A.R.G. was supported by F31 NS067758 and A.R.G. and S.J.M. were supported by T32 MH067564. The work was also supported by NIH RO1 NS35180, NS-046064, NS-077601, and the Howard Hughes Medical Institute. A.R.G., S.J.M., and N.S. designed the experiments. A.R.G. and S.J.M. collected the electrophysiological data, A.R.G. collected the morphological data, and

A.R.G. and E.B.B. performed the immunostaining and imaging. A.R.G. analyzed the data, with input from N.S. and help from W.L.K. to perform the cluster not and principal component analyses. A.R.G., B.B.M., and N.S. wrote the manuscript, with input from the other authors. “
“The NAc plays a major role in the generation of motivated behaviors (Berridge, 2007; Ikemoto, 2007; Nicola, 2007). It is thought to facilitate reward seeking by integrating dopaminergic reinforcement signals with glutamate-encoded environmental stimuli (Brown et al., 2011; Day et al., 2007; Flagel et al., 2011; Phillips et al., 2003; Stuber et al., 2008). A prominent idea is that the glutamate input to the NAc encodes the context, cues, and descriptive features that characterize any given moment in time (Berke and Hyman, 2000; Everitt and Wolf, 2002; Kelley, 2004; Pennartz et al., 2011). Together, glutamate and dopamine can promote synaptic plasticity, which is thought to be a crucial neural mechanism in the NAc by which pertinent environmental cues become more salient than other stimuli (Kheirbek et al., 2009; Sun et al., 2008; Wolf and Ferrario, 2010).

Previous work indicates

that stimulation of the alveus evokes at least two forms of recurrent inhibition, with a single stimulus recruiting primarily somatic and proximal dendritic inhibition, whereas brief trains (as used in the study by Müller and colleagues) also recruit a distal dendritic form of inhibition mediated by stratum oriens and lacunosum-moleculare (OL-M) cells ( Pouille and Scanziani, 2004). The somatic and proximal dendritic inhibition evoked by alveus stimulation is likely to be mediated by a variety of interneuron subtypes, including axo-axonic selleck compound cells, which target the axon initial segment, basket cells, which are primarily somatic, and bistratified cells, which target oblique and basal dendrites ( Somogyi and Klausberger, 2005). To generate dendritic spikes, the authors use local glutamate iontophoresis targeted to oblique and basal dendritic branches. Consistent with earlier work using glutamate uncaging (Losonczy et al., 2008), they find that glutamate iontophoresis generates localized dendritic spikes in a subset of basal and apical oblique branches of hippocampal CA1 pyramidal neurons. These

local dendritic spikes can be detected at the soma as an abrupt change in the rate of rise of the somatic membrane potential, and they had similar properties to events generated by glutamate uncaging or www.selleckchem.com/products/Paclitaxel(Taxol).html local synaptic stimulation. Presumably the authors chose to use glutamate iontophoresis rather than uncaging in these experiments because of the capacity of caged glutamate to block GABA receptors (Fino et al., 2009). As observed previously (Losonczy et al., 2008), the authors find that these dendritic spikes come in two classes, weak and strong, with strong Calpain dendritic spikes more effective in generating action potential output. The main new finding from the study (Müller et al., 2012) is that while recurrent inhibition is effective in blocking the

generation of weak dendritic spikes, it is ineffective in blocking the generation of strong dendritic spikes. The authors go on to show that this is also the case after conversion of weak dendritic spikes to strong dendritic spikes following the pairing of dendritic spikes with bursts of somatic action potentials. Finally, the authors investigate the impact of recurrent inhibition during theta-burst stimulation, used to mimic the natural theta rhythm, showing that an activity-dependent reduction in inhibition during theta-burst stimulation reduces the capacity of inhibition to block the generation of dendritic spikes. The data show that recurrent inhibition is relatively ineffective in blocking the generation of strong dendritic spikes, which begs the question: What is it about these events that makes them so powerful? Previous work indicates an important role of dendritic A-type potassium channels in regulating the strength of localized dendritic spikes in hippocampal CA1 pyramidal neurons (Losonczy et al., 2008).

6 ± 16.2 pA, mean ± SD, n = 5). Synaptic release of neurotransmitters is triggered by Ca2+ influx via presynaptic voltage-gated calcium channels (VGCCs). VGCCs are enriched inside the AZ (Bucurenciu et al., 2008, Harlow et al., 2001, Holderith et al., 2012, Sheng et al., 2012 and Sun et al., 2006), where

they are an integral part of the exocytosis machinery (Cao et al., 2004, Han et al., 2011, Kaeser et al., GSK2656157 cost 2011 and Mochida et al., 2003), providing for direct coupling between Ca2+ entry and neurotransmitter release. Accumulating data argue that VGCC activity is regulated at the level of individual small presynaptic boutons and that this mechanism contributes to target-specific adjustment of Quisinostat presynaptic strength (Ermolyuk et al., 2012, Holderith et al., 2012 and Koester and Johnston, 2005). However, until now direct electrophysiological recordings of presynaptic VGCCs were only possible in large synapses such as the calyx of Held or hippocampal mossy fiber bouton (Bischofberger et al., 2006 and Schneggenburger and Forsythe, 2006). To assess properties of VGCCs in small presynaptic boutons, we first attempted HPICM-targeted cell-attached recordings from the exposed bouton surface. To optimize the recording conditions for the detection of VGCCs, we used a Ba2+-containing pipette solution and switched the bath to a

high K+ extracellular solution to collapse the resting membrane potential of neurons (Delmas et al., 2000) (Experimental Procedures). Strikingly, we found no evidence for VGCCs in 44 bouton patches with unmodified scanning nanopipettes and in 21 patches

with widened (broken) pipettes at different parts of the exposed surface of small boutons (e.g., Figure 5A). Twelve of these patches nevertheless contained identifiable anion channels (data not shown). We estimate that PDK4 the density of VGCCs on the exposed surface of axonal boutons was less than six channels per bouton (σσ < 3.9 channels per μm2, Monte Carlo simulations with 99% confidence interval; Figure S3). Despite the absence of detectable VGCCs on the exposed surface of boutons, we readily recorded Ca2+ channels in postsynaptic dendrites (in 2 out of 17 patches, corresponding to an estimated upper limit of the average channel density between 2 and 21 channels per μm2; Figure 5B and Figure S3). The apparent absence of VGCCs on the exposed surface of presynaptic boutons is in full agreement with recent findings that the overwhelming majority of functional VGCCs in central synapses are located in the AZ (Bucurenciu et al., 2008, Holderith et al., 2012 and Sheng et al., 2012). In contrast to the cell-attached recordings, we readily detected VGCC activity in whole-bouton recordings (when conditions were optimized for VGCC detection, see Experimental Procedures), with access to the whole membrane of a presynaptic bouton including the AZ (Figures 5C–5E).

Only English language publications which included children and adolescents aged 4–18 years old were included. How active are obese children? Are they less active than their non-obese counterparts? It would seem that regardless of the measurement device, (accelerometry, heart rate measurement, or doubly-labeled water), the obese children generally exhibit lower levels of activity. For example, Maffeis and colleagues14 used heart rate monitoring to estimate PA in a small group of 8–10-year-old obese (body GSK1120212 mouse mass index (BMI) >97th percentile) and non-obese children. Non-obese children spent about 100 min a day more being physically active (all activity above sedentary behavior) than the obese children. Moderate

Selleck CH5424802 to vigorous PA was similar in the two groups, so the difference in total daily activity was accounted for by light intensity activity. The authors also found that the obese children spent more time (approximately 100 min a day) engaged in sedentary pursuits compared to the non-obese children. These findings are similar to Yu et al.15 who also used heart rate derived estimates of energy expenditure to compare total activity (activity above sedentary

behavior) and sedentary behavior between 18 obese (BMI ≥95th percentile) and 18 non-obese 6–18-year-olds. The obese youngsters in Yu et al.’s15 study spent 30% less of the monitored time engaged in physically active pursuits (no data are provided for the breakdown of light, moderate or vigorous activity), but 51% more time engaged in sedentary activities during the waking hours. Accelerometry studies also found lower PA levels in obese youngsters. In a group of 53 obese (BMI ≥98th percentile) and 53 non-obese boys and girls (mean age 8.6 years), Hughes and colleagues16

found total activity time (mean accelerometer counts/min) others was lower in the obese (648 counts/min) compared to non-obese children (729 counts/min). Interestingly there was no difference in time spent being sedentary between the two groups of children in this study. When the proportion of the time spent engaged in activities of moderate to vigorous intensity was compared this was marginally less (2.4%) in the obese (average of about 16 min a day) compared to the non-obese (average of about 23 min a day). Similarly, Page et al.17 found that time spent being moderately to vigorously active was slightly less in 14 obese (BMI >99th percentile; average of about 10 min a day) compared with 54 non-obese (average of about 13 min a day) 10-year-olds. Although total activity and PA are generally less in the obese children and adolescent compared to the non-obese, total activity energy expenditure is not always reduced. Ekelund et al.18 assessed total activity energy expenditure and PA using a combined doubly-labeled water and accelerometer approach in 18 obese (BMI >30 kg/m2) and 18 non-obese adolescents.

However, MVR introduces the additional possibility of vesicle release desynchronization within each release site. To test whether frequency-dependent depression in EPSC peak amplitude and accompanying kinetic changes require MVR, we lowered extracellular Ca2+ to promote the fusion of, at most, one vesicle per release site, or univesicular release (UVR). Under these conditions, the amplitude of EPSCs was 68.5 ± 3.4% (n = 6) smaller. Increasing CF stimulation frequency from 0.05 Hz to 2 Hz caused a

similar reduction of the EPSC peak amplitude and its current-time integral (40.0 ± 3.0% and 36.0 ± 2.9% decrease, respectively; Figure 2; n = 18; p > 0.05) because there was no change in the EPSC kinetics. Neither the EPSC rise (0.42 ± 0.02 LBH589 chemical structure and 0.44 ± 0.02 ms; p > 0.05) nor decay (2.6 ± 0.2 and 2.6 ± 0.2 ms; p > 0.05) was altered by increasing the stimulation frequency from 0.05 to 2 Hz (Figures 2B and 2C). These results suggest that activity-dependent slowing of EPSC kinetics requires MVR because it is not present under conditions of UVR. We also 3-MA nmr recorded EPSCs in an extracellular solution that more closely approximates the [Ca2+] in vivo (Borst, 2010). The peak EPSC amplitude was reduced by 43.3 ± 5.6% when the extracellular [Ca2+] was lowered from 2.5 to 1 mM (n = 7). Increasing the stimulation

frequency from 0.05 Hz to 2 Hz slowed the EPSC rise time from 0.37 ± 0.02 ms to 0.46 ± 0.05 ms (n = 7; p < 0.01), suggesting that MVR desynchronization persists in an extracellular [Ca2+] solution similar to in vivo

conditions. Because extracellular [Ca2+] can contribute to the presynaptic action potential waveform (Schneggenburger et al., 1999), we also reduced MVR through activation of metabotropic glutamate receptors (mGluRs) that Adenylyl cyclase suppress transmitter release (Takahashi et al., 1996). The mGluR agonist L-CCG-I (20 μM) reduced the peak EPSC amplitude by 50.6 ± 5.7% (n = 7), qualitatively similar to lowering extracellular Ca2+ to 0.5 mM, where UVR predominates. In L-CCG-I, increasing CF stimulation frequency from 0.05 Hz to 2 Hz no longer slowed the EPSC rise or decay (n = 7; p > 0.05; ANOVA), further suggesting that activity-dependent kinetic changes require MVR. The lack of kinetic changes under conditions of UVR supports the notion that desynchronization of multiple vesicles released within each release site, or intrasite vesicle desynchronization, underlies EPSC kinetic slowing. Vesicle depletion predicts that during UVR, when transmission is constrained to the release of zero or one vesicle with each action potential, frequency-dependent synaptic depression is due to fewer active sites. With this limitation, the synaptic glutamate transient will not be altered during depression. We tested this idea by monitoring the inhibition of EPSCs with a low-affinity AMPAR antagonist, kynurenic acid (KYN). In 0.

However, recent

work suggests the possibility of subdivisions within the PPA. A retinotopic Dasatinib research buy mapping study identified not one but two such maps in the PPA (Arcaro et al., 2009). In addition, a recent functional connectivity study found that fMRI activity in posterior PPA was more strongly coupled to activity in occipital lobe visual regions, while activity in anterior PPA was more strongly coupled to activity in parietal lobe regions implicated in spatial processing (Baldassano et al., 2013). Although these divisions need to be further explored, it is possible that human PPA is a compound of two functionally differentiable regions that are physically split into LPP and MPP in the macaque. In addition to establishing this possible homology, Kornblith et al. (2013) also explore questions about the kind

of information coded by macaque scene regions. Although some progress has been made in this direction in humans using fMRI adaptation and MVPA, the current study goes further, with some intriguing results. For example, the stimuli that most strongly activate the scene-selective neurons in LPP and MPP appear to have a common visual feature: long, straight contours. Although the response in LPP (but not MPP) to the nonscene stimuli (objects and textures) that contained long, straight contours was still lower than the response to scenes, this finding is suggestive http://www.selleckchem.com/products/Vorinostat-saha.html about the types of low-level features that might be used for scene perception. Another even more important observation is that LPP and MPP neurons respond to both spatial and nonspatial features of scenes. This PD184352 (CI-1040) was established by examining neuronal response to a synthetic room presented stereoscopically, shown with different wall textures (“wallpaper”) and objects, and from different viewing angles and distances. Neuronal firing rates in LPP and MPP were modulated by all of these factors, with the strongest modulations caused by differences

in texture. This last result deserves some comment. Early work on the PPA suggested that it was especially concerned with processing the spatial layout of scenes. Results from some recent studies have supported this idea (Kravitz et al., 2011 and Park et al., 2011). However, other studies have found evidence that the PPA codes nonspatial aspects of scenes such as texture and objects (Cant and Xu, 2012 and Harel et al., 2013). Kornblith et al. (2013)’s finding that viewpoint, depth, texture, and object can all be decoded based on multiunit responses in LPP (with somewhat weaker performance in MPP) is broadly consistent with these human fMRI results, indicating representation of both spatial and nonspatial features in the PPA. Nevertheless, the finding that LPP and MPP response is dominated by texture, rather than by spatial features (i.e., viewpoint and depth), is at first glance surprising.

However, note that conjunction inference via the minimum t statistic is valid even when the conjoined contrasts are not independent

( Nichols et al., 2005). We also used the right-hemisphere portion of the mask of nucleus accumbens (right being the side on which we have previously observed stronger RPE activity; e.g., Daw et al., 2006b and Wittmann et al., 2008) to define the ROI selleckchem for two analyses conducted with the MarsBaR ROI toolbox (Brett et al., 2002). First, average activity from the region was extracted and subjected to the same analysis as described above, to produce Figure 3F. Second, the activity from the region was subject to a second regression analysis using a different design, which tagged the first-stage onset of each trial with an impulse regressor of one of five types: switches (trials on which the opposite first-stage choice from the one on the previous trial was made) and stays (four types of events modeling all combinations of the factors reward versus nonreward and common versus rare transition in the previous trial). An additional nuisance www.selleckchem.com/screening/pi3k-signaling-inhibitor-library.html regressor was included at the time of outcomes. Per-subject effect sizes for the four stay regressors were subject to a 2 × 2 repeated-measure ANOVA, and, additionally, the value for each subject of the contrast measuring the interaction

of the two factors ([reward/common minus nonreward/common] minus [reward/rare minus nonreward/rare]) was correlated with the weight given to model-based values (the estimated parameter w) from the behavioral fit. The authors are grateful to Yael Niv, Dylan Simon, Aaron Bornstein, Seth

Madlon-Kay, Bianca Wittmann, Bernard Balleine, Jan Gläscher, and John O’Doherty for helpful conversations and advice. This work was in part supported by a McKnight Scholar Award (N.D.), NIMH grant 1R01MH087882-01, part of the CRCNS program (N.D.), a NARSAD Young Investigator Award (N.D.), the Gatsby Charitable Foundation (P.D.), and a Wellcome Trust Programme Grant to R.J.D. “
“Deciphering the neural code has triggered many investigations Cytidine deaminase and debates over the past decades. Both firing rate and temporally governed spike patterns of individual neurons or neuronal ensembles have been shown to provide means to encode information in brain circuits. In hippocampal principal cells, the distribution of firing rate across an environment is skewed such that each cell, referred to as a “place cell,” tends to fire in a specific location (spatial firing field or “place field”), leading to the classical view that hippocampal place maps represent space in the form of a rate code. Hippocampal place maps, however, are flexible: changing environments and task demands lead to “remapping” phenomena in which the neural code is altered to mirror the animal’s experience.