001 ± 0.041 SEM; Vcarb/tail = 0.096 ± 0.031; Vamph = 0.031 ± 0.019; V ureth = −0.032 ± 0.09; pureth = 0.9; pcarb/tail = 0.025; pamph = 0.043; pMK = 0.7; t test). With EV, we observed significant replay after stimulation only in the amphetamine condition click here (p < 0.05; paired t test), although EV had a tendency to have higher values than the control data (reverse EV)

for other experimental conditions (see Figures S6B–S6E). It should be noted that EV is insensitive to fine-scale temporal spiking patterns and thus provides different information from that obtained with latency measures or template matching. Memory formation is one of the most important processes in the brain, yet the neuronal dynamics underlying this process are only beginning to be understood, partly due to the technical

difficulty of recording from large neuronal populations in behaving animals. Here, we report that the hallmarks of memory formation and memory replay—stimulus-induced sequential activity patterns that reactivate spontaneously—can also be observed in urethane-anesthetized rats. In this preparation, Selleck Trichostatin A population recordings and other brain manipulations can be more easily performed, thus providing a convenient model for electrophysiological study of mechanisms, leading to formation of sequential patterns implicated in memory processes. Furthermore, we found similar replay in both somatosensory and auditory cortices, suggesting this may be a general mechanism in the cortex. Although previous studies using voltage-sensitive dye imaging in anesthetized animals have shown that ongoing Edoxaban spontaneous activity can reflect stimulus-evoked spatial patterns on a coarse spatial scale (Han et al., 2008 and Kenet et al., 2003), our findings provide a major refinement of these results by demonstrating replay of fine-scale sequential spiking patterns (Figures 2 and 3) that is more analogous to sequential spiking patterns observed during memory replay in freely moving animals

(Euston et al., 2007, Hoffman and McNaughton, 2002, Kudrimoti et al., 1999, Skaggs and McNaughton, 1996 and Wilson and McNaughton, 1994). In addition, our study indicates the importance of brain state during stimulus presentation. Although multiple studies show that most memory replay occurs during synchronized states (e.g., during slow wave sleep; Battaglia et al., 2004 and Xu et al., 2012), the importance of the brain state during encoding is not clear. It is known that electrically evoked LTP is suppressed in this state ( Leonard et al., 1987), so there is a precedent for our current finding that presentation of stimuli during a desynchronized state as compared to the synchronized state is significantly more effective in inducing lasting reorganization of temporal patterns ( Figures 2 and 6), which subsequently results in stronger spontaneous replay of stimulus-induced patterns.

The SSD was tuned for each rat so that it would erroneously continue its movement (STOP-Failure) or successfully stop on approximately equal numbers of trials. During each test session, SSD was held constant to facilitate analysis of the electrophysiological data triggered on the GO and STOP cues. Rats received implants containing 21 individually drivable tetrodes (Gage et al., 2010). For the Immediate- and Deferred-GO tasks, tetrodes were targeted to right M1, STR, and GP. For rats trained on the Go/NoGo and Stop-signal tasks, the left

BG (STR, GP, STN, and SNr) were targeted. Ipsilateral prefrontal ECoGs were recorded with skull screws in contact with the brain (AP 4.5 mm, ML 1.5 mm relative to bregma). All signals were referenced to Lapatinib a skull screw on the midline 1 mm posterior to lambda (between cerebral cortex and cerebellum). We have found previously that this reference location is not itself associated with substantial beta power, that would produce artificially elevated beta coherence estimates between all pairs of forebrain locations (Berke, 2009). Analyses were performed using Matlab (Mathworks, Inc., Natick, MA). Gabor power spectrograms

were computed by convolving LFPs with Gaussian-tapered (50 ms standard deviation) complex sinusoids of integer frequencies from 1 to 100 Hz, and taking the logarithm of the squared magnitude of the resulting time-series. To generate Figures 1C and Figures

4C, the spectrograms for each recording session were averaged. To generate power comodulograms (Figures 2D and Figures S3B), Pearson’s correlation coefficient VX-770 order was calculated between these same time series for each pair of recording sites. This resulted in a heptaminol 100 × 100 grid with each point having a value ranging from −1 (perfect anticorrelation of power at two frequencies) to +1 (perfect correlation of power at two frequencies). Only epochs during which the rat was engaged in the task (from initial nose poke to trial completion) were included. Power spectra (Figure 2C) were calculated for each trial, averaged across trials to give a mean spectrum at each recording site for each session, and smoothed with a three-point rectangular sliding window. To calculate coherence spectra, for each trial we calculated the cross-spectrum between each pair of recording sites. Session-wide coherence was then calculated as the squared magnitude of the averaged trial-by-trial cross spectra normalized by the product of the average autospectra (Figure 2E). See Figures 1D, Figures 3B, 3E; Figures 4D; Figures S2, S5. LFPs were zero-phase filtered between 15–25 Hz and the analytic signal was calculated using the Hilbert transform. The squared magnitude of the analytic signal is a continuous measure of beta power, and continuous beta phase was extracted as the argument of the analytic signal.

02). When expressed relative to the protein levels of Shh in the conditioned media,

the VEGF/Shh ratio was also lower in VegfFP-he than VegfFP-wt mice (37.7 ± 7.0 in VegfFP-wt versus 12.4 ± 4.3 in VegfFP-he; mean ± SEM, n = 7–3; p = 0.015). Immunostaining of spinal cord cross-sections from VegfFP-he embryos for Robo3 to identify precrossing Alpelisib solubility dmso commissural axons revealed that these axons exhibited abnormal pathfinding, were defasciculated and projected to the lateral edge of the ventral spinal cord ( Figures 2A–2E). Such aberrant commissural axon pathfinding was rarely observed in VegfFP-wt control embryos ( Figures 2A and 2C). Quantitative analysis confirmed that the area occupied by Robo3+ axons was larger and that these guidance defects were more frequent in VegfFP-he than VegfFP-wt embryos ( Figure 2F). Thus, floor plate-derived VEGF is necessary for normal guidance of precrossing spinal commissural axons in vivo. The commissural axon guidance defects in VegfFP-he embryos were not secondary to altered expression of Netrin-1 or Shh, because ISH analysis at E11.5 showed that the pattern and level of expression of Netrin-1 and Shh were comparable

in VegfFP-he and VegfFP-wt embryos ( Figures S2A–S2D). Because VEGF signals via Flk1 to regulate cerebellar granule cell migration (Ruiz de Almodovar et al., 2010) and axon outgrowth (Ruiz de Almodovar et al., 2009), we assessed whether selleck chemical Thalidomide commissural neurons expressed this receptor. It is well established that neurons express Flk1 at much lower levels than endothelial cells, rendering in situ detection of Flk1 in neurons challenging (Ruiz de Almodovar et al., 2009, Ruiz de Almodovar et al., 2010 and Storkebaum et al., 2005). Nonetheless, genetic and pharmacological loss- and gain-of-function studies

established that Flk1 signals important biological processes in neurons (Bellon et al., 2010, Ruiz de Almodovar et al., 2009 and Ruiz de Almodovar et al., 2010). In fact, it has been postulated that this differential expression of VEGF receptors allows VEGF to exert effects on neurons without inducing angiogenesis (Storkebaum et al., 2005 and Zacchigna et al., 2008). To maximize detection of Flk1 expression in neurons, we used a panel of techniques. We first determined the expression of Flk1 in precrossing commissural axons by taking advantage of anti-Flk1 antibodies (#SC6251 and #SC504) that detect Flk1 selectively in neurons but not in endothelial cells, presumably because of different posttranslational modifications of the receptor in these different cell types (Marko and Damon, 2008, Ruiz de Almodovar et al., 2010 and Storkebaum et al., 2010). Spinal cord sections from E13 rat embryos (corresponding to E11.

Our findings suggest that plasticity in adult V1 may be mediated in part by disinhibition of specific excitatory inputs. To enable the visualization of inhibitory synapses onto pyramidal neurons in the visual cortex of intact animals, E16.5 embryos were electroporated in utero with plasmids driving the expression

of GFP-gephyrin and a cytoplasmic red fluorescent protein (DsRed-Express, referred to as RFP). This resulted in the presence of scattered, red fluorescent pyramidal neurons in layer 2/3 of the adult visual cortex that carried green GFP-gephyrin puncta (Figure 1A). We first wished to confirm that these GFP-gephyrin puncta actually represented inhibitory synapses in vivo as has previously been shown in cell culture (Dobie and

Craig, 2011 and Meier and Grantyn, 2004). To this Anticancer Compound Library ic50 end, we performed electron microscopy (EM) of sections immunogold-labeled with antibodies to GFP. We detected GFP-gephyrin in synapses on spines and shafts (Figure 1B). As described for endogenous gephyrin (Sassoè-Pognetto et al., 1999 and Sassoè-Pognetto et al., 2000), GFP-gephyrin was found at and in the direct vicinity of the postsynaptic specialization where it may be associated with surface-localized or endocytosed GABA receptors (van Rijnsoever et al., 2005). Because the immunoreaction product (diaminobenzidine and gold particles) tended to mask the postsynaptic specialization of labeled synapses as previously observed C59 wnt (Sassoè-Pognetto et al., 2000), we classified symmetric and asymmetric synapses based on the width of their synaptic cleft (Gray, 1959). We found that in unlabeled else synapses the sizes of the clefts of symmetric (16.1 ± 2.5 nm) and asymmetric (28.7 ± 2.7 nm) synapses

were clearly distinguishable (p < 0.001, Figure 1C). The clefts of GFP-gephyrin-labeled synapses were comparable (16.9 ± 3.5 nm) to those of nonlabeled symmetric synapses in the same material (Figure 1C). Of all GFP-gephyrin labeled synapses, 92% showed a cleft corresponding to that of a symmetric synapse (Figure 1D). The other 8% had a cleft comparable to that of asymmetric synapses (which does not rule out the possibility that despite of this they were in fact GABAergic). Next we performed immunohistochemical staining for the vesicular GABA transporter (VGAT), a marker for inhibitory presynaptic terminals, on sections of V1 of RFP and GFP-gephyrin expressing mice. This confirmed that the vast majority of GFP-gephyrin puncta were juxtaposed to VGAT puncta on distal dendrites (88%, p < 10−5 compared with 43% chance level of juxtaposition assessed by shifting the image of the VGAT channel 14 pixels) (Figure 1E). The actual percentage of juxtaposition could be somewhat higher or lower, as on the one hand not all inhibitory boutons may be detected using VGAT labeling, while on the other we may have also detected coincidental juxtaposition.

The task has correct answers, from which we constructed an index of the ToM ability of each participant. We then extracted the percentage of signal change in dmPFC in response to CPV during

bubble markets (in the 8 mm sphere centered at [9, 50, 28]) for each subject and found a substantial correlation between that signal change and each subject’s ToM ability index (Spearman rank correlation coefficient ρ = 0.57; p < 0.05) (Figure 4). Critically, no significant correlation between dmPFC signal and the ToM index was found during nonbubble markets (ρ = 0.32; p > 0.1). Furthermore, we repeated the same analysis in vmPFC (in the 8 mm sphere centered at [3, 53, −2]), which showed that activity in vmPFC did not correlate with performance in the ToM task in either the bubble (ρ = 0.06; p > 0.5) or the nonbubble markets (ρ = 0.09;

p > 0.5). Taken Raf inhibition together, these findings supported our hypothesis that the increased activity in dmPFC that we isolated during the financial bubbles reflected a computation associated with the participants’ tendency to make inferences about the mental states of other players in the market. An intriguing possibility is that participants during the financial bubble, rather than mentalizing the intentions of individual players, would represent the whole market as an intentional agent in the attempt DAPT supplier Urease to forecast the future intentions of the market. Notably, unlike in vmPFC, activity in dmPFC isolated in this contrast did not correlate significantly (ρ = 0.009; p > 0.5) with the individual’s susceptibility to ride a financial bubble, as measured by the bubble susceptibility index. These results suggested that the neural circuit that modulated the value representation in vmPFC (associated with the behavioral susceptibility to ride a financial bubble) might be influenced by the social computations instantiated in dmPFC during the update of participants’ CPV. In order to test this hypothesis,

we then conducted a psychophysiological interaction (PPI) analysis between vmPFC and dmPFC. This analysis revealed that the functional coupling between these two regions significantly increased during bubble markets (p < 0.001; Figure 5), suggesting that investors might update their portfolio profits in vmPFC by taking into account the intentions of the other players in the market. We therefore devised a model-based analysis to investigate this idea in more detail. To study how intentions modulate market traders’ computations, we studied how subjects inferred intentional agency from changes in the arrival of buy and sell orders. Recall that subjects see a fast-motion replay of all orders to buy (bids), and all orders to sell (asks), which were entered in the original behavioral experiments.

Willem Van der Does is supported by a grant from the Netherlands Organisation of Science (NWO-MaGW) (VICI-grant # 904-57-132). The funding sources have no involvement in designing of the study and the preparation of the manuscript. Mumtaz Jamal and Willem Van der Does designed the study. Mumtaz Jamal carried out the data analysis and wrote the draft of the manuscript. Willem Van der Does, Brenda Penninx, and Pim Cuijpers participated in designing the NESDA study and in commenting and editing of the manuscript. see more MJ, PC and BWJHP report no financial relationships with commercial

interests. AJWVDD received an advisory panel payment from Roche Pharmaceuticals (unrelated to this study). “
“The authors regret that errors were presented in the above published paper, which are addressed below. In this paper, we surveyed all-cause and specific-causes mortality between the years 1999-2008, among opioid-dependent users treated at methadone maintenance treatment (MMT) clinics in Israel. Table 1 showed the number KU-55933 clinical trial of deaths and crude mortality rates (CMRs) per 100 person-years with the respective 95% confidence intervals (CIs) by demographic characteristics. The original table indicated that Jews and others comprised 1,983 (20.2% of the sample) and Israeli-Arabs comprised 7,835 (79.8%) of the study sample. We found, however, that the figures were incorrect and that the

correct figures are that Jews and others comprised 7,835 (79.8%) of the population, while Israeli-Arabs comprised 1,983 (20.2%) of the sample. The correct Table 1 presented below. This correction did not change the conclusions of the paper. The authors would like to apologise Vasopressin Receptor for any inconvenience caused. “
“Regular cannabis use has been associated with a wide range of mental health problems including psychotic disorders (Arseneault et al., 2002 and Moore et al., 2007), externalizing problems (aggressive and delinquent behaviour) (Fergusson et al., 2002 and Monshouwer et al., 2006) and, to a lesser extent, internalizing problems, such as depression (Degenhardt et al., 2001, Degenhardt et

al., 2003 and Patton et al., 2002) and anxiety (Patton et al., 2002, van Laar et al., 2007 and Hayatbakhsh et al., 2007a). Several hypotheses have been put forward to explain these associations, including the “damage hypothesis”, which proposes that cannabis use precedes mental health problems (Brook et al., 1998 and Kandel et al., 1992) and the “self medication hypothesis”, which proposes that individuals with mental health problems tend to resort to drug use to sooth their problems (Khantzian, 1985). The “shared causes hypothesis” proposes that the linkage between cannabis use and mental health problems is the result of genetic and environmental factors associated with both problem behaviour and cannabis use (Fergusson and Horwood, 1997, Fergusson et al., 2002 and Shelton et al., 2007).

Perfusion of afoxolaner produced a dose-dependent BMS-354825 research buy inhibition in the GABA response with an IC50 value of 3.7 nM as shown in Fig. 6. This inhibition failed to reverse

following extended saline washout. In Drosophila, resistance to cyclodiene insecticides is associated with a single amino acid substitution of serine for alanine at residue 302 of the rdl gene ( Ffrench-Constant et al., 2000). Xenopus oocytes expressing A302SRDL were challenged with afoxolaner at 0.1, 1, and 10 nM to compare potency relative to that observed with wtRDL. As shown in Fig. 7, there was no statistically significant difference observed between wtRDl and A302SRDL at any of the concentrations, suggesting that no cross-resistance would be expected between isoxazolines and cyclodienes.

As shown in Fig. 8, afoxolaner was highly potent on Canton-S flies with an LD50 value of 0.2 μg/vial (95% Metabolism inhibitor confidence interval = 0.1–0.4 μg/vial). Although this insecticide is an order of magnitude less potent against the susceptible strain than dieldrin (LD50 value of 0.02), excellent potency was observed against the RDL strain, as predicted by the receptor studies. RDL flies exhibited comparable sensitivity with a resistance ratio value (RR, expressed as RDL LD50/Canton-S LD50) of only two. In contrast, the RDL flies exhibited strong resistance to dieldrin (RR > 5000) consistent with earlier reports (Bloomquist, 1993). Based on the mode of action and differences in receptor interaction, it is unlikely that fleas and ticks carrying the rdl gene mutation and thereby resistant to dieldrin will demonstrate

cross-resistance to afoxolaner. Data generated in these research studies provided evidence of the safety and month-long effectiveness of afoxolaner against fleas and ticks on dogs following oral administration all at 2.5 mg/kg. The in vitro discovery results showed that afoxolaner was more potent than any other compound ever tested in this membrane feeding system, including the avermectins ( Zakson et al., 2001). This in vitro assay was not only an important tool for estimation of compound potency in the discovery process, but established a preliminary in vivo target of 0.16 μg/ml as a blood level required in a dog for complete flea effectiveness for 30 days. The 0.16 μg/ml level was chosen because it provided 100% control at the 24 h in vitro observation and a 24 h in vivo challenge was to be used for fleas on dogs. In subsequent work conducted with formulated afoxolaner in dogs, the EC90 for fleas was determined to be 0.023 μg/ml ( Letendre, 2014). With strong evidence that blood containing afoxolaner could effectively control fleas, Study 2 was initiated and represented the first time afoxolaner was evaluated in a dog (n = 1). That study revealed effectiveness of afoxolaner against both fleas and ticks beyond a month following a single 2.5 mg/kg oral administration.

The overlap of RGC dendrites was quantified as overlap=2∗(A∩B)A+Bwhere A and B represent the smallest convex polygons encompassing the arbors of the respective RGCs in a z projection and A ∩ B indicates the area of their intersection. We used either Wilcoxon-Mann-Whitney rank-sum or, in case of paired samples, Wilcoxon signed-rank tests to assess statistical significance of differences between groups. Throughout the text population averages are given as mean ±

standard error of the mean (SEM). We thank members of the Kerschensteiner Lab and Dr. Peter Lukasiewicz for helpful discussions and comments on the manuscript. We are grateful to Dr. Peter NVP-BGJ398 purchase Lukasiewicz for lending us equipment for focal agonist applications and to Dr. Felice Dunn for advice on bipolar cell recordings in retinal flat mount preparations. This work was supported by grants from the Whitehall

Foundation (D.K.), Edward Mallinckrodt Jr. Foundation (D.K.), Alfred P. Sloan Foundation (D.K.), Research to Prevent Blindness Foundation (Career Development Award to D.K. and unrestricted grant to the Department of Ophthalmology and Visual Sciences at Washington University), the NIH (R01 EY021855 to D.K.; P30 EY0268 to the Department of Ophthalmology and Visual Sciences see more at Washington University), and the NSF (DGE1143954, A.A.). A.A. and D.K. planned and performed the experiments, analyzed the data, and wrote the manuscript. “
“Understanding the processes that initiate and terminate critical periods for receptive field plasticity is a subject of intense investigation. The initiation of the critical period for ocular dominance plasticity is many widely believed to be triggered by the maturation of inhibitory synapses targeting the somata of principal neurons in the visual cortex (Hensch et al., 1998, Huang et al., 1999 and Di Cristo et al., 2007). Increased perisomatic inhibition would reduce excitability in principal neurons, enabling mechanisms of activity-dependent synaptic plasticity to discriminate between

inputs from the two eyes (Jiang et al., 2007, Toyoizumi and Miller, 2009 and Kuhlman et al., 2010). The activation of inhibitory gamma-aminobutyric acid (GABA) receptors would also limit activity at N-methyl-D-aspartate (NMDA) receptors and restrict subsequent induction of synaptic plasticity at excitatory synapses onto principal neurons (Kirkwood and Bear, 1994, Rozas et al., 2001, Artola and Singer, 1987 and Jang et al., 2009). The evidence supporting the idea that maturation of inhibition determines the timing of the critical period is based on experimental manipulations of inhibitory output. For example, promotion of the early maturation of inhibitory synapses onto principle neurons induces a precocious initiation of the critical period (Huang et al., 1999, Di Cristo et al., 2007 and Sugiyama et al., 2008).

5, as was previously reported (Stainier and Gilbert, 1990). The primary vascular plexus is already formed at this time and is intermingled with the incoming axons until E11.5 (Figure 1B). Around

E12.5, a ring-like structure of axonal innervation forms around each whisker primordium, while vessels remain disorganized and partially intermingled with the check details axons (Figures 1C, 1G, and 1H; Figure S1A available online; Movie S1). By E14.5, vessels are recruited to the nerve ring, leading to close apposition of vessels and axons (Figures 1D and S1B; Movie S2). By E16.5, a prominent double ring structure is formed, with a ring of nerves on the inside, a ring of vessels on the outside, and a defined space between them (Figures 1E and S1C; Movie S3). At E18.5, both nerve and vessel ring patterning are further refined Ruxolitinib in vivo (Figure 1F). The nerve-inside and vessel-outside structure is maintained during

adulthood and is known to be important for whisker function (Ebara et al., 2002). This relatively simple system with clear stereotypic developmental characteristics (Figure 1I) allows us to dissect the molecular and cellular interactions between nerves and vessels in a systematic, stepwise manner. Based on the developmental profile of nerve and vessel organization in the whisker follicle, the “one-patterns-the-other” model of neurovascular congruency would predict that the trigeminal axons attract surrounding blood vessels to establish the double ring structure. To examine this possibility, we analyzed the nerve/vessel organization in the whisker follicle of neurogenin-1 (Ngn1) knockout embryos, in which trigeminal ganglia (TG) and thus the trigeminal isothipendyl nerves are completely absent (Ma et al., 1998). To our surprise, vessel ring organization is completely normal in Ngn1 knockouts at E16.5 ( Figure 2B), despite the lack of nerve ring formation (absence

of green signal in Figure 2B). Both the size and position of the vessel ring in Ngn1 mutant and wild-type littermate controls has no detectable difference ( Figures 2C and 2D). This result clearly demonstrates that unlike limb skin ( Mukouyama et al., 2002), where arterial patterning is disrupted in Ngn1/2 knockouts, indicating that sensory axons determine the patterning of arteries, here the formation of the vascular ring structure is independent of the nerves. Next, we examined whether blood vessel ring patterning has any effect on nerve ring formation. We analyzed the double ring structure in endothelial-specific neuropilin-1 (Npn-1) null mice (Tie-2 Cre; Npn1flox/flox) where the vasculature surrounding the whisker follicles is poorly developed ( Figures 2E and 2F) ( Gu et al., 2003). However, nerve ring formation shows no detectable difference between mutants and control littermates ( Figures 2G and 2H). This result demonstrates that nerve ring formation is also independent of vessel ring formation.

03, p = 0.6 for velocity and r2 = 0.02, p > 0.72 for acceleration). Correlations of firing rates between different arms indicate that the population of mPFC single units is capable of representing anxiety-related

task components. However, such correlations do not quantify the extent to which the firing pattern of any given single unit is paradigm-related. To address this issue, we first binned each spike train into three-second segments, and calculated the influence DNA Damage inhibitor of arm type (open versus closed) on firing rate by ANOVA. 29/69 (42%) of the recorded neurons fired significantly differently (p < 0.05) to the closed and open arms by ANOVA . Next, to confirm that the observed frequency of task-related firing patterns in the population of single units was not due to chance, an EPM score was calculated for each unit. The EPM score is a normalized ratio of Akt inhibitor the average difference in firing rates across arms of the same type, compared to the average differences in firing rates across arms of different types (see Experimental Procedures). The resultant measure, which varies from −0.33 to 1, indicates the degree to which that unit’s firing pattern represents the “open vs. closed” structure of the EPM. Units with positive EPM scores closer to 1 represent

this structure well; units with EPM scores near or below zero do not. Accordingly, the correlation of firing rates across arms of the same type was higher in units with positive EPM scores than in units with negative EPM scores (Figures 4A and 4B). Furthermore, single units with a significant effect of arm type on firing in the ANOVA had higher

EPM scores than other units (mean score = 0.3 ± 0.06 and 0.064 ± 0.04 for units with and without significant main effects of arm type), demonstrating the found utility of the EPM score as a quantification of the strength of paradigm-related activity. We next examined whether the distribution of EPM scores obtained in our sample (Figure 4C) could have been obtained by chance, using a bootstrap method. Briefly, 500 simulated spike trains were generated for each unit. The location of each spike was assigned randomly from the actual path of the animal in the maze when that spike was recorded, and EPM scores were computed from these simulated spike trains. The distribution of simulated EPM scores (Figure 4C, red line) was significantly different from the experimental distribution (p < 0.0001, Wilcoxon’s rank-sum test), due to the presence of a greater fraction of units with positive (i.e., paradigm-related) EPM scores in the experimental distribution. These results confirm that the paradigm-related firing patterns seen in our sample in the standard EPM were unlikely to have arisen by chance. In cognitive tasks, mPFC unit activity predicts future choice behavior (Fujisawa et al., 2008, Peters et al., 2005 and Rich and Shapiro, 2009).