g., hip, knee, and ankle joints).47 Emerging evidence in studies in children and adolescents indicates a relationship between coordination of movements, better cognition48 and brain activation.49 For example, Chang et al.49

separated individuals into a moderate or low intensity soccer course that emphasized coordination in movement training. Participants demonstrated faster reaction times and higher response accuracy in cognitive performance in both exercise intensity groups compared with a baseline group, suggesting that light exercise that is not sufficient to enhance fitness could nevertheless improve cognition. In addition, following coordination training, both groups exhibited PLX 4720 a greater P3 amplitude and a shorter P3 latency in neuroelectrical indices, which indicate that the coordinative exercise itself increases the allocation selleck compound of attentional resources and the efficiency of neurocognitive processing during the performance

of a cognitive task. The findings of Chang et al.49 provided a potential explanation for improved cognition following mild intensity Tai Ji Quan training; however, whether the positive relationship between movement coordination and brain activation could extend to older adults requires further examination. During Tai Ji Quan class, instructors and students experience substantial psychosocial interaction. Although Wayne and Kaptchuk50 noted that they did not find any studies that focused on isolating the social effects of Tai Ji Quan (i.e., examining conditions with and without social support) in their review, they argued that Tai Ji Quan should be recognized as an

intervention with significant potential for community-based social support. Interestingly, a recent study Fossariinae proposed by Mortimer et al.51 has identified the association between Tai Ji Quan and social interaction, and this positive linkage has even extended to brain function. Following four groups (i.e., Tai Ji Quan, walking, social interaction, and control groups) over 40 weeks of intervention revealed significant improvements in dementia scales and neuropsychological assessments that measured basic information processes (e.g., Trail Making Test A), learning (e.g., Auditory Verbal Learning Test), and executive function (e.g., Trail Making Test B) in both Tai Ji Quan and social interaction groups but not in the walking or control groups, suggesting that social interaction within Tai Ji Quan may play an essential role in facilitating cognitive performance. Beneficial effects were also identified by MRI measurement, which found Tai Ji Quan and social interaction groups had significant mean percentage changes in normalized whole brain volume.

Surprisingly, however—given that the CS had no action relevance—the neurons maintained a sustained response to the CS during the ensuing delay. Moreover, as seen for the behavioral effect, this persistent response did not reflect global changes in arousal or motivation, but a spatial bias toward or away from the CS location. Sustained activity following a CS+ was higher at the cue location relative to the opposite location, suggesting that attention lingered at the CS+ location (Figure 5C, top, black versus gray trace). By contrast, sustained activity following a CS− was lower at

the cue’s location relative to the opposite location ( Figure 5C, bottom), consistent with the behavioral suppression at the CS− location. The CS− evoked inhibition interfered with Pifithrin-�� molecular weight the monkeys’ performance and lowered their rate of reward. Nevertheless, the CP673451 effects grew rather than abating with training and, in both neural responses and behavior, were larger after familiar relative to novel CS ( Figure 5D, bottom versus top). Moreover,

after prolonged training the effects seemed to involve plasticity of the early visual response, since they became insensitive to context and automatically transferred to a different task in which the pretrained CS no longer predicted reward ( Figure 5E). These findings describe a correlate of “attention for liking” phenomena described in behavioral research, whereby attention is automatically biased by the reward (conditioned) stimulus associations. The findings are consistent with several—not

mutually exclusive—mechanisms. One possibility is that they are related to the phenomenon of inhibition of return, whereby attention is inhibited Carnitine dehydrogenase from revisiting recently examined locations (e.g., Mirpour et al., 2009). A related possibility is that they reflect specific reinforcement mechanisms. The value-dependent orienting described in Figure 5 may arise through a modulation of visual activity by a dopamine reward prediction error response (e.g., Figure 3B) which, like the responses in the parietal lobe, is excitatory for a positive and inhibitory for a negative reward predictive cue. This modulation may also differ from that underlying goal-directed control in that it acts in model-free rather than model-based fashion. As I discussed in the previous section, a model-based allocation would assign priority to the target in the Peck et al. (2009) task, since this was the stimulus that was informative for the future action. A model-free mechanism by contrast would assign priority to the initial CS, since this was the stimulus that signaled a change in reward expectations. Regardless of the specific answers to these questions (which remain to be determined by future research), the findings highlight the critical point that reward may influence attention through several distinct mechanisms.

31329008-31439638) was targeted in an OmniBank® 129/SvEv embryonic stem cell (ES) clone (OST448976) with the OmniBank gene trapping vector VICTR 48+MTII (Lexicon Pharmaceuticals, Inc., The Woodlands, TX). The exact location of the insertion was determined by inverse PCR to be position 6970 bp in intron 1 of the primary RNA transcript of the muskelin gene locus. Most gene trap vectors disrupt endogenous messages and create null alleles ( Zambrowicz et al., 1998). Blastocyst

injections were performed at Lexicon Pharmaceuticals, Inc. ES cells used for injection were 129SvEvBrd agouti. Resulting chimeras were bred to C57BL/6 albinos. Heterozygous mice were backcrossed to C57/129 hybrid agouti. For PCR genotyping of offspring mice, the forward Ibrutinib and reverse primers (A + B) detect the wild-type allele. Primer A was used in combination with a gene trapping vector specific reverse primer (A + C) to amplify Dasatinib in vivo a mutation-specific product that contains 96 nucleotides of OmniBank®

vector sequence. Oligonucleotide primers (A, 5′-AGCTACTTAAACCAAGTCAATGAGG-3′; B, 5′-CTCATATGGTCATTTCAATATAGAGC-3′; and C, 5′-ATAAACCCTCTTGCAGTTGCATC-3′) were used in an equimolar multiplex reaction to amplify corresponding Mkln1 alleles on mouse chromosome 6. Cycling conditions were 94°C for 15 s, 65°C for 30 s (−1°C/cycle), 72°C for 40 s (10 cycles), followed by 94°C for 15 s, 55°C for 30 s, and 72°C for 40 s (30 cycles). To confirm the genetic manipulation, we performed Southern blot analysis on SacI-digested genomic DNA. A radiolabeled probe was generated with primers A and B (described above). Digestion of amplified fragments with BamHI resulted in a probe specific to positions 6697–6907 (Blast, NCBI) of the primary muskelin transcript upstream of the Ketanserin vector insertion site. Because of an additional vector SacI restriction site, the radiolabeled probe detects a 6.8 kb (KO) and 16.7 kb (wild-type) fragment. We thank J.C. Adams for critical comments on the

manuscript and for sharing unpublished information. We are grateful to P. Zelenka for providing a muskelin-specific antibody. We thank the members of the network grant DFG-FG885 and K. Duncan for technical help and critical comments. We also thank E. Kronberg and T. Grundmann for excellent help with animal housing. This study was supported by National Institutes of Health grant NINDS NS060698 to E.L.F.H. and by the University of Hamburg Medical School, DFG grants KN556/1-1, KN556/1-2, KN556/1-3, FG885-KN556/4-1, and FG885-KN556/4-2, the Chica and Heinz Schaller Foundation, and the Hamburg State Excellence Initiative: “Neurodapt” to M.K. “
“Constructing a unified sensory percept from diverse forms of primary receptor input is a challenge faced by all sensory systems, including olfaction (Gottfried, 2010). Among the senses, olfaction is particularly synthetic, as chemical mixtures are commonly perceived as a single unified odor object (Gottfried, 2010, Livermore and Laing, 1996 and Wilson and Stevenson, 2003).

, 2006, Howarth and Attwell, 2006 and Paulson and Newman, 1987). However, the current generated by glutamate transport is small compared to that generated by astrocytic K+ uptake at the synaptic cleft in olfactory glomeruli (De Saint Jan and Westbrook, 2005), and it seems unlikely that the blockade of a comparatively small current would reduce functional hyperemia as much as observed. Second, CBF may increase as a result of metabolic activation induced by glutamate uptake. Sodium/glutamate

cotransport consumes energy for the restoration of the ionic gradient by the Na+-/K+-ATPase, and for the conversion of glutamate to glutamine. While the contribution of these processes to the brain’s energy

budget is small (Attwell and Laughlin, 2001), glutamate Selleckchem BI-2536 uptake into astrocytes also directly initiates astrocytic nonoxidative glycolysis and lactate release (Pellerin, 2005). Lactate itself may initiate vasodilation (Gordon et al., 2008), but it is also possible that sodium ions cotransported into astrocytes with glutamate may trigger a vasoactive click here pathway. Sodium ions shuttled into astrocytes by this cotransport propagate as interastrocytic sodium waves in cell cultures (Bernardinelli et al., 2004), and they have also been shown to couple synaptic activity and astrocytic nonoxidative glucose consumption (Voutsinos-Porche et al., 2003). This stimulation of nonoxidative glycolysis in astrocytes is thought to underlie the disproportionate rise of CBF and glucose compared to a smaller increase in oxygen consumption—the mismatch that forms the basis of functional brain imaging (Magistretti and Pellerin, 1999). Therefore, glutamate transport into astrocytes may simultaneously activate functional hyperemia and nonoxidative glycolysis in astrocytes, and may contribute to the high temporal and spatial correlation of

CBF increase and glucose consumption observed in functional brain imaging (Raichle and Mintun, 2006). Advances in imaging and cellular manipulation may be harnessed to overcome the TCL uncertainties regarding the role of astrocytic molecular agents in functional hyperemia. Optical imaging during physiological activity can, in principle, be extended to any small molecule for which there is an appropriate fluorescent indicator (Zhang et al., 2002). Genetic manipulations may also be valuable, particularly if the perturbations can be performed in a cell-type-specific and temporally precise manner (Kennedy et al., 2010). Methods to stimulate or downregulate the expression of genes, such as those for glutamate transporters, specifically in mature astrocytes are increasingly becoming available (Colin et al., 2009).

CBT alone in cocaine-dependent patients. Following informed consent, patients completed a two-week baseline assessment. Patients were then randomly assigned to one of the two treatment arms using computerized random numbers. The allocation sequence was provided in sealed envelopes and thus blind to the researchers and patients. After group allocation, patients received a 12-week intervention phase Temozolomide (CBT + prizeCM

or CBT alone, week 1–12) followed by a 12-week maintenance phase (CBT + prizeCM or CBT alone, week 13–24). Six months after the last visit, patients were re-invited for a follow-up assessment and received a remuneration of 20$ for their participation (week 48). Patients were excluded by the study investigator and counted as drop-outs if they were absent for 3 consecutive weeks without any excuse. Dropout patients had the possibility of receiving a standard

treatment in other treatment centers in the region of Basel. Patients received 18 manual-guided individual CBT sessions for 24 weeks, in accordance with the CBT manual by Dürsteler-MacFarland et al. (2010), as based on the CBT manual by Carroll (1998). In the first 12 weeks, the 60-min therapy sessions took place weekly and urine samples were Akt inhibitor collected twice weekly. In weeks 13 to 24, the therapy sessions took place every second week and urine samples were collected weekly. Urine samples were collected and analyzed before CBT sessions and performed by the same therapist. Patients received an immediate feed-back about the results of their urinalyses. Urinalyses were tested onsite for the cocaine metabolite benzoylecgonine with the drug screen from Stephany Diagnostika GmbH (Germany). Therapy sessions were conducted by qualified psychologists and psychiatrists trained in the CBT manual for cocaine dependence, found all of whom were experienced in treating substance use disorders. All sessions were rated by therapists and audiotaped and supervised

weekly to monitor adherence to protocol. To monitor clinicians’ skill level, CBT sessions were videotaped monthly and rated by masters’-level independent evaluators. Prize-based CM was performed according to the protocol by Petry (2000) for the entire 24 weeks. According to the frequency of submitted urine samples patients in the EG had the chance to earn prizes twice weekly in the intervention phase (1–12 week) and weekly during the maintenance phase (13–24 weeks). For submitting a cocaine-negative urine sample participants had the chance to earn prizes of different magnitudes. Patients could draw from a bowl with 500 chips, of which 250 were non-winning. 219 had a value of 2$ (mini prizes: food supplies or hygiene articles), 30 a value of 20$ (medium prizes: vouchers), and the jumbo prize had a value of $500 (television or holiday vouchers).

The average magnitude of the noise (or signal) correlation is less critical to encoding, however, than the relationship between the noise and signal correlation (Averbeck et al., 2006; Gu et al., 2011; Wilke and

Eurich, 2002). Although no form of response pooling can dissipate positive noise correlations SCH 900776 nmr between similarly tuned neurons (positive signal correlation), subtractive pooling can dissipate positive noise correlations between dissimilarly tuned neurons (negative signal correlation). Thus, learning could improve population coding by altering the relationship between the signal correlation and noise correlation. To test whether the relationship between signal and noise correlations depends on task relevance, we directly compared these two measures for each pair of neurons in our data set. The example neurons depicted in Figures 2C–2J suggest that although task relevance can influence both signal and noise correlations, it does so following a specific relationship. We thus asked whether noise correlations systematically covary with signal correlations, and whether this depends on task relevance. We found that each class of motifs exhibited a correlation between signal and noise

correlations, but the sign of this relationship depended on task relevance. For task-relevant motifs, this relationship was negative (Spearman correlation coefficient: r = −0.15, p = 0.051, Figure 4A): Dolutegravir chemical structure larger signal correlations were accompanied by smaller noise

correlations. For task-irrelevant and novel motifs, in contrast, the relationship was positive (task irrelevant: r = 0.19, p = 0.012; novel: r = 0.23, p = 0.0022; Figures 4B and 4C): larger signal correlations were accompanied by larger noise correlations. The difference between these relationships was highly significant (ANCOVA motif class × regression slope interaction, p = 7.9 × 10−5). In from contrast, we found no effects of learning on the relationship between mean firing rate and noise correlation and the relationship between distance between neurons and noise correlation (Figures S3A and S3B). The relationship between signal correlation and noise correlation thus depends strongly on the learned task relevance of the motif. This dependence is particularly apparent in neuron pairs that have strong (either positive or negative) signal correlations (Figures 4D and 4E). Among neuron pairs with strong positive signal correlations (>0.4), the task-irrelevant and novel motifs evoked significantly larger noise correlations than the task-relevant motifs (Kruskal-Wallis test, p = 0.0038; Figure 4D). In contrast, among neuron pairs that had large negative signal correlations (<−0.4), the task-irrelevant and novel motifs evoked significantly weaker noise correlations than the task-relevant motifs (Kruskal-Wallis test, p = 0.032; Figure 4E).

, 2006 and Richardson and Pichaud, 2010), we observed that injection of crb2 MO at the dosage used in the present study enhanced the her4 mRNA expression at 24 hpf ( Figures 4Af–4Ah). These results suggest that the Crb⋅Moe complex is critically involved in the regulation of Notch signaling. Since the activity of Notch signaling was significantly reduced Selleck PD0332991 in the moerw306 mutant, we expected that the number of mitotic cells in the moerw306 hindbrain would

also be reduced because of accelerated differentiation of neuroepithelial cells into postmitotic neurons. However, in the moerw306 mutant, the number of dividing cells positioned away from the apical surface per sectioned hindbrain was significantly increased ( Figures 4Ba and 4Bc), Epigenetics inhibitor while the total numbers of mitotic cells per sectioned hindbrain was similar between the WT and moerw306 mutant ( Figure 4Bd). Overexpression of Crb2 also increased the number of ectopically mitotic cells ( Figures S2Aa–S2Ac). This result is consistent with the previous reports that Moe inhibits Crb ( Laprise et al., 2006, Laprise et al., 2009 and Laprise et al., 2010). In considering this discrepancy between the reduced Notch activity and the increased number of ectopically proliferating cells, we suspected that the neuroepithelial cells were converted to another type of neural progenitor. Recently,

it has been reported that an insufficient level of the Notch signal facilitates the differentiation of neuroepithelial cells, which

undergo mitosis only in the apical area, to INPs, which proliferate in a more basal area of the mammalian cortex ( Mizutani et al., 2007). To investigate whether the reduced Notch activity seen in the moerw306 mutant had a similar effect, we examined the expression of the Tbr2 transcription factor, a marker of INPs in the mouse cortex ( Mizutani et al., 2007). Casein kinase 1 The embryonic spinal cord of the Tg(vsx1:GFP) transgenic zebrafish expresses GFP in the cells that generate two mature neurons by cell divisions away from apical area, indicating that these cells are functionally equivalent to the mammalian INPs ( Kimura et al., 2008). Immunoreactivity of Tbr2 in GFP-positive mitotic cells in the Tg(vsx1:GFP) transgenic zebrafish suggests that Tbr2-immunoreactivity can also be used as a maker for INPs in zebrafish ( Figures S2Ba–S2Bd). In the moerw306 hindbrain, basally localized mitotic cells expressed Tbr2 ( Figures 4Ca–4Cf), and the number of Tbr2-immunoreactive mitotic cells was significantly increased in the moerw306 mutant hindbrain ( Figure 4Cg). In the WT, four of nine basally located pH3-positive cells were Tbr2-positive (16 sections, four embryos). In the moerw306 mutant, 21 of 24 basally located pH3-positive cells were Tbr2-positive (17 sections, four embryos).

, 2008; Figure S3). In contrast,

overexpression Cabozantinib nmr of NR2B could not rescue the synaptic loss of NR2A in kif17−/− neurons, suggesting that KIF17-mediated NR2B trafficking is required to maintain the synaptic level of NR2A ( Figure S4). We also examined the localization of Mint1, and a redistribution of Mint1 out of synapses, with accumulation in the soma, was observed in kif17−/− mouse neurons ( Figures S5A–S5C). The synapse density and the localizations of synaptophysin, GluR1, and cyclic-nucleotide gated ion channel (CNGA2, a candidate KIF17 cargo; Jenkins et al., 2006) were unchanged in kif17−/− mouse neurons ( Figures 2A, 2D, and S5D–S5K). These results suggest selective reductions in the number of NR2B/2A-containing synapses and the amount of synaptic NR2B/2A in the dendrites of kif17−/− mouse neurons. Next, we investigated the possible alteration in receptor trafficking in kif17−/− mouse neurons by live imaging of NR2 subunits tagged with EGFP ( Barria and Malinow, 2002). NR2B-EGFP or NR2A-EGFP was coexpressed along with untagged NR1 (splice variant NR1-1a) in cultured hippocampal selleck products cells because assembly with the NR1 subunit is essential for NR2 subunits to be transported from

cell bodies to synapses ( Fukaya et al., 2003). NR2B and NR2A were overexpressed to similar extents in kif17+/+ and kif17−/− neurons ( Figures S6A and S6B). Time-lapse recordings revealed that most NR2B clusters (90%) were moving in kif17+/+ neurons ( Figures 2G–2J; Movie S1). Motility was categorized into three groups (vibrating, anterograde, and retrograde) ( Figure 2I). The velocity of anterogradely Oxalosuccinic acid transported

clusters in kif17+/+ neurons was 0.71 ± 0.04 μm/s ( Figure 2J), which is comparable to that of KIF17 movement described in a previous report ( Guillaud et al., 2003). By contrast, in kif17−/− neurons, fewer NR2B-EGFP clusters (49%) were mobile ( Figure 2I) and the velocity of anterogradely transported clusters was decreased (0.22 ± 0.02 μm/s) ( Figure 2J) compared with that in kif17+/+ neurons. Cell-surface expression of NR2B-EGFP in kif17−/− neurons was reduced compared with that in kif17+/+ neurons ( Figures S6C and S6D). On the other hand, movement of NR2A-EGFP was not affected by disruption of the kif17 gene ( Figures 2K–2N; Movie S2). Together, these data suggest that transport of NR2B is impaired in kif17−/− mouse neurons but that of NR2A is unchanged. To further gain insight into the molecular events underlying the changes in the levels of NR2A/NR2B in kif17−/− mice, we first examined the turnover rate of NR2 subunits in kif17−/− hippocampal cultures treated with cycloheximide (20 μg/ml), a translational inhibitor ( Hatanaka et al., 2006).

1 is the only known factor specifically expressed within MGE by all progenitors in the ventricular zone (VZ) and subventricular zone (SVZ) (Flames et al.,

2007 and Marín and Rubenstein, 2001). In addition, Lhx6 and Er81 are expressed in subdomains of MGE and CGE (Figure 2A) (Flames et al., 2007 and Butt et al., 2008). We have generated inducible CreER drivers targeting these transcription factor genes (see Table 1 and Table 2). Although several Nkx2.1 transgenic lines have been generated expressing a constitutive Gemcitabine in vitro form of Cre (Fogarty et al., 2007 and Xu et al., 2008), they deviate from the spatiotemporal pattern of endogenous Nkx2.1 to varying degrees, and offer no temporal control over Cre activity. In contrast, our Nkx2.1-CreER driver appeared to precisely recapitulate the endogenous expression and allows temporal regulation of Cre activity, thereby establishing reliable genetic access to the MGE progenitors ( Figure 2). E12 tamoxifen induction resulted in robust labeling of the VZ and SVZ progenitors in MGE and POA but not lateral ganglionic eminence (LGE) ( Figures 2B and 2C). Low-dose tamoxifen induction (0.5 mg/30 g body weight) further revealed radial columns of cells, which likely represent putative

progenitor clones in MGE ( Figure 2D). Consistent with previous studies ( Miyoshi et al., 2007), E12 induction gave rise to cortical GABA neurons expressing parvalbumin (PV), somatostatin (SST), but not vasoactive intestinal peptide (VIP) ( Figures 2J–2L). Recent studies demonstrate Trametinib that Nkx2.1 expression continues beyond mid-gestation and persists many in the ventral ridge of SVZ during late embryonic and postnatal ages (Marin et al., 2000 and Magno et al., 2009). Indeed,

we found Nkx2.1-Cre activity in ventral SVZ beyond E17 ( Figures 2E–2G), when the characteristic eminence of MGE had already fused with the adjacent LGE. This raised the issue of whether these ventral SVZ cells derived from earlier MGE or acquired Nkx2.1 expression independently. We found that these Nkx2.1+ cells continued to incorporate BrdU labeling at E17 (administered 4 times every 4 hr) and thus retained mitotic competence, which is a key indication of progenitor properties. Using genetic fate mapping, we further demonstrated that Nkx2.1+ progenitors in ventral SVZ derived from earlier progenitors in MGE (e.g., from E12 MGE progenitors; Figures 2H and 2I) but not the LGE. Members of the Dlx family of homeobox transcription factors, Dlx1, Dlx2, Dlx5, and Dlx6, are expressed mainly in the SVZ of embryonic LGE, MGE, and CGE (Eisenstat et al., 1999). Dlx genes continue to express in subsets of GABAergic neurons in embryonic, postnatal, and mature brains, and have been implicated in regulating their migration, differentiation, survival, and function ( Cobos et al., 2005, Cobos et al., 2007 and Long et al., 2009). Whether and how different members control the development and function of subpopulations of interneurons is not well understood.

The trained NVHL rats were significantly better than the exposed NVHL rats in sessions 2–4, indicating that adolescent training promoted adult cognition. We then compared the trained NVHL and the trained control rats to assess whether adolescent cognitive training was normalizing. The two groups did not differ (Figure 2C), suggesting that adolescent cognitive training improved cognitive control to normal. We verified that the improved cognitive performance of NVHL rats in the T-maze was due to adolescent training by retesting

all the rats on the Screening Library concentration two-frame place avoidance task (Figure 2D). The NVHL rats that were trained as adolescents were not impaired, but the NVHL rats that were only exposed to the rotating arena as adolescents were consistently impaired in avoiding both the original shock zone (Figure 2D, left) and the reversed shock zone in the conflict avoidance test (Figure 2D, right). Only the exposed NVHL rats were significantly impaired, compared to the other groups, in both the original and reversed shock zones (p values < 0.05). We conclude that adolescent cognitive training has adult procognitive effects that include preventing cognitive control deficits following a neonatal lesion and that this benefit can generalize to other tests of cognition. Physical changes in

the degree of the adult hippocampal lesion could not account for the cognitive benefits of adolescent training because there was no correspondence between lesion extent and cognitive performance (Figure 3). Although the adolescent-trained and adolescent-exposed Thiamine-diphosphate kinase NVHL rats show similar degree of lesion of septal, intermediate, and temporal hippocampus, cognitive performance SB203580 in vitro was markedly different. We then tested whether early cognitive training caused functional changes, focusing on neural synchrony, which may be disturbed in patients with schizophrenia (Gandal et al., 2012; Moran and Hong, 2011; Uhlhaas and Singer, 2010). Local field potentials (LFPs) in hippocampus and the medial prefrontal cortex (mPFC) of adult control rats

were compared from recordings during home cage behaviors and during the two-frame task to first identify changes that were related to cognitive performance. Neural synchrony between two electrode locations was measured as the frequency-specific phase locking value (Figure S2). In sham control rats, compared to being in the home cage, performing the task produced a robust increase of interhippocampus phase synchrony across delta, theta, and beta frequencies but not gamma (Figure 4A). These changes were specific to hippocampus because no such differences were found in either inter-mPFC or inter-hippocampus-mPFC synchrony (Figure S3). Because interhippocampus synchrony was related to two-frame performance but synchrony involving the mPFC was not, we focused on hippocampal synchrony in further analyses. We then compared interhippocampal synchrony of adult control and NVHL rats while they were performing the two-frame task.