Yet another pattern of foot strike use is reported for the Tarahumara, a minimally shod population of traditional farmers living in the Sierra Madre Occidental of Northwestern Mexico.13 The Tarahumara are renowned endurance runners, running 75 km or more

in traditional ball games and, in recent years, competing in ultramarathons.14 Tarahumara traditionally wore simple rawhide sandals (huaraches), and many continue to do so today, although some have adopted conventional running shoes. 13 Lieberman 13 reported that 89% of Tarahumara who wear conventional shoes habitually RFS, while Tarahumara who wear traditional huaraches tend to MFS or FFS. In this study we examined foot strike patterns and running kinematics among traditional Hadza hunter-gatherers in Northern Tanzania. Imatinib purchase As described in detail elsewhere,15 traditional Hadza subsist almost entirely on wild check details foods, hunting and gathering each day on foot and with simple hand tools. Traditional Hadza have no agriculture, livestock, or machinery. Women typically walk 6 km each day gathering wild berries, tubers, and other plant foods, while men walk an average of 11 km per day, hunting small and large game with bow and arrow, and gathering honey.15 and 16 The landscape they inhabit is semiarid savannah with a patchy

mix of forest and grassland cover; the ground is often rocky, and low craggy hills are common. While the Hadza are highly active, they rarely run.15 Musiba and colleagues17 conducted a study of walking gait and foot dimensions among substrate level phosphorylation traditional Hadza. As discussed in that report, Hadza adults typically wear simple sandals made from repurposed tire rubber, common throughout East Africa. These sandals have relatively thin (∼1 cm) soles that offer protection from sharp rocks

and thorny plants but do not provide any cushioning or elevate the heel. Traditional Hadza can therefore be categorized accurately as “minimally shod”, and their feet display many of the same features (e.g., splayed toes, greater foot width) evident in habitually unshod populations.17 and 18 While Musiba and colleagues17 did not examine running, self-selected speeds during walking trials reported for Hadza adults (1.15 m/s) were relatively fast compared to other traditional, unshod populations, and the Hadza also used greater stride frequencies and stride lengths. We used high-speed digital video to analyze foot strike patterns and limb-segment angles of Hadza adults and juveniles running at a range of speeds. Our objectives were to determine the frequency of RFS, MFS, and FFS among the Hadza, to investigate the effects of speed and age on foot strike patterns, and to compare these data to published values for the Kalenjin and Daasanach. We predicted that the Hadza, who lack the training and experience in endurance running common among the Kalenjin, would exhibit foot strike patterns more similar to the Daasanach.

Taken together, our study shows that RIM proteins coordinately regulate Ca2+ channel targeting, vesicle docking and priming, and Ca2+ channel-vesicle colocalization at the presynaptic active zone. For the generation of calyx-specific conditional KO mice, we have made use of recently generated floxed mouse lines for RIM1αβ (Kaeser et al., 2008) and RIM2αβγ (Kaeser et al., 2011) and of a previously available Cre knockin mouse line in the Krox20 locus (Voiculescu et al., 2000). The presynaptic neuron pool that generates the large calyx of Held nerve terminals onto MNTB neurons is located in the contralateral ventral cochlear nucleus (VCN) and is largely represented

by globular bushy cells (Cant and Benson, selleck chemicals llc selleck chemicals 2003). Krox20 is a transcription factor that is highly specifically active in rombomeres 3 and 5 of the developing hindbrain (Voiculescu et al., 2000), which give rise to a majority of neurons in the VCN (Farago et al., 2006 and Maricich et al., 2009). We found homogeneous phenotypes among the recorded

calyx of Held synapses, which indicates, together with morphological analysis (Figure 1B; L. Xiao, N. Michalski, and R.S., unpublished observations; Renier et al., 2010), that the entire population of calyx of Held-generating neurons stems from Krox20Cre-positive neurons. Thus, the Krox20Cre mouse line enables the conditional removal of floxed alleles at the calyx of Held synapse, which will make it a useful tool to advance our understanding also of other proteins of the presynaptic vesicle cycle. Using direct presynaptic recordings at the nerve terminal, we demonstrated that RIM proteins are essential for localizing Ca2+ channels to the active zone, as shown by the clear decrease in the presynaptic Ca2+ current density in RIM1/2

2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase cDKO calyces. These direct recordings at the nerve terminal show that RIMs determine presynaptic Ca2+ channel density without changing major biophysical parameters of Ca2+ channel gating, although we cannot exclude that RIMs influence Ca2+ channel inactivation with prolonged pulses (>50 ms, Figure 2; Kiyonaka et al., 2007); this, however, will be relevant only for prolonged presynaptic AP trains. Analyzing RIM-dependent presynaptic Ca2+ channel targeting has been limited because previously no KO mice deleting all RIM1/2 isoforms were available (Schoch et al., 2002 and Calakos et al., 2004) and because previously investigated synapses, including the C. elegans neuromuscular synapse ( Koushika et al., 2001), did not allow for measurements of presynaptic Ca2+ currents. Using cultured RIM1/2 cDKO neurons, Kaeser et al. (2011) have observed an ∼2-fold reduction in Ca2+ transients in presynaptic boutons during an AP. This, together with our finding that presynaptic APs are unchanged ( Figure 2), is evidence for a reduced Ca2+ channel density also at small bouton-like synapses.

In brief, binding of glutamate to NMDARs coupled with depolarization of the postsynaptic membrane, which relieves the magnesium channel block, results in the entry of calcium through the NMDAR and a rise in spine calcium ( Figure 1) ( Nicoll et al., 1988). Around

this time, Ito et al. (1982) reported that pairing cerebellar climbing fiber stimulation with parallel fiber stimulation caused a long-term depression (LTD) of parallel fiber responses as well as to the responses to iontophoretically delivered glutamate. Selleckchem SCH-900776 Ten years later NMDAR-dependent LTD was discovered in the hippocampus ( Dudek and Bear, 1992). Hippocampal LTP and LTD and cerebellar LTD are arguably the most studied forms of synaptic plasticity and are the primary focus of this review. Much of the first half of this period was consumed by the debate over whether LTP expression is due to an increase in glutamate release or an increase in the postsynaptic sensitivity to glutamate (Bliss and Collingridge, 2013, Bredt and Nicoll, 2003 and Nicoll and Roche, 2013). The discovery of silent synapses

and their unsilencing during LTP (Isaac et al., 1995 and Liao Akt activation et al., 1995) provided a postsynaptic explanation for the decrease in synaptic failure rate during LTP, the strongest evidence for a presynaptic expression mechanism. This turned the tide of public opinion to a postsynaptic expression mechanism. Perhaps the most definitive demonstration of a postsynaptic expression mechanism comes from glutamate uncaging experiments (Harvey and Svoboda, 2007 and Matsuzaki et al., 2004), in which repetitive activation of NMDARs on see more a single spine results in a long-lasting increase in the uncaging

AMPAR response from the same spine. In addition to the increase in AMPAR responses the spine volume increases and follows the same time course as the enhancement in the AMPAR response. Interestingly, most manipulations that block structural plasticity also block LTP. Thus, structural plasticity has often been used as a proxy for LTP. These findings do not exclude an additional presynaptic mechanism, but since the magnitude of the enhancement found in the uncaging experiments is similar to those found with pairing synaptic stimulation with postsynaptic depolarization, there is no need to invoke a presynaptic component, at least during the first hour, the time window most studied. Much of the research on LTP during the past decade has focused on the role of CaMKII in LTP (Lisman et al., 2012) and AMPAR trafficking (Anggono and Huganir, 2012, Kessels and Malinow, 2009, Lüscher and Malenka, 2012 and Nicoll and Roche, 2013). Considerable evidence indicates that CaMKII is the primary downstream target following calcium entry through the NMDAR and is both necessary and sufficient for LTP. Two interesting areas of research concern the activity-dependent translocation of CaMKII to the synapse and the role of CaMKII as a memory molecule.

, 2009). In summary, our quantification of the functional organization of the interneuron network places important constraints PLX-4720 cell line on the construction of any network model of the cerebellum (Bower, 2010, Gleeson et al., 2007 and Maex and De Schutter, 2005) and should inspire many future experiments exploring the consequences of this structured connectivity for cerebellar cortical function. All experiments were carried out in accordance with the animal care and handling guidelines approved

by the UK Home Office. Sagittal slices of cerebellar cortex were obtained from 18- to 23-day-old rats. Slices were placed in a recording chamber perfused with standard artificial cerebrospinal fluid that contained 125 mM NaCl, 2.5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 25 mM NaHCO3, 1.25 mM NaH2PO4, and 25 mM D-glucose and was bubbled with carbogen (95% oxygen, 5% carbon dioxide), giving a pH of 7.4. Neurons were visualized with an upright microscope (Zeiss Axioskop) using infrared differential interference contrast (DIC) optics, optimized as described previously (Davie et al., 2006). Interneurons were identified by their soma size (10–12 μm) and SCH772984 their location in the molecular layer. Simultaneous whole-cell patch-clamp recordings were made at 32°C ± 1°C from up to four MLIs distributed throughout the vertical extent of the ML (Figure S8).

Glass pipettes (7–10 MΩ) were filled with intracellular solution containing 130 mM K-methanesulfonate, 10 mM HEPES, 7 mM KCl, 0.05 mM EGTA, 2 mM Na2ATP, 2 mM MgATP, and 0.5 mM Na2GTP, titrated with KOH to pH 7.2. The resulting reversal potential for

chloride was ECl− = –77.5 mV. Biocytin (0.5%) was added to the intracellular solution to label the cells. Recordings were typically made at least 30–40 μm below the surface of the slice to minimize the number of cut axons (Figure S2A). The relative position of each recorded cell in the ML below was identified using the DIC image, and the intersomatic distances were read out using the stage position. MLI morphologies were reconstructed using the TREES toolbox in MATLAB (Cuntz et al., 2011), after histochemical labeling and confocal microscopy. For further details, see the Supplemental Experimental Procedures. Data analysis was performed using Igor Pro (Wavemetrics), MATLAB (MathWorks), and Python. The probability of an electrical (pE) or chemical (pC) connection is defined as the ratio between the total number of observed connections and the total number of possible connections. For each experimentally measured pair, there is one possible electrical connection and two possible chemical connections, therefore: pE=nE/npairspE=nE/npairs pC=nC/(2∗npairs)pC=nC/(2∗npairs)where nE is the total number of electrical connections, nC is the total number of chemical connections, and npairs is the total number of pairs tested. To count the occurrence of triplet patterns, all quadruplets were divided into four triplets.

(2011). Degree (strength) was calculated Trichostatin A as the sum of binary (weighted) edges on a node at a given threshold. Participation coefficients and within-module Z scores were calculated after Guimerà and Nunes Amaral (2005) on thresholded graphs. Relevant formulas are provided below. Degree for node i   is defined as ki=j∑Aijki=∑jAij, where AijAij is the adjacency matrix of the graph. Within-module Z score for node i   is defined as zi=êi−ê¯si/ósi, where êiêi is the number of edges of node i   to other nodes in its module sisi, ê¯si is the average of êê over all the nodes in sisi, and ósiósi is the standard deviation of êê in sisi. Participation index for node i   is defined as Pi=1−∑s=1NM(êis/ki)2, where êisêis is the number

of edges of node i   to nodes in module s  , kiki is the degree of

node i  , and NMNM is the total number of modules in the graph. In Figure 6, the areal graph was analyzed at nine thresholds (10%–2% edge density in 1% steps), and the participation coefficients arising from InfoMap community assignments were summed and plotted as the proportion of the theoretical upper bound attainable over thresholds. In Figure 7, the modified voxelwise network was analyzed at five thresholds (2.5%–0.5% edge density in 0.5% steps; these thresholds all displayed complex community structure and focal articulation points, see Figure S4), and the number of unique communities present within a certain radius of the selleck antibody center of a source voxel was calculated using InfoMap community assignments. Radii of 5–10 mm in 1 mm steps were sampled. Thus Figure 7 shows the results pooled from ifoxetine 30 analyses (5 thresholds × 6 radii; each analysis normalized to its maximal value). MRI preprocessing and RSFC processing were performed with in-house software. Network calculations were performed

in Matlab (2007a, The Mathworks, Natick, MA). Brain visualizations were created with Caret software and the PALS surface (Van Essen, 2005 and Van Essen et al., 2001). Consensus assignments from Power et al. (2011) are available at http://sumsdb.wustl.edu/sums/directory.do?id=8293343&dir_name=power_Neuron11. The real-world graphs presented in Figure 3, Figure 4, and Figure S1 are publicly available data sets (http://www-personal.umich.edu/∼mejn/netdata/). The citations for the networks are as follows: yeast protein, Jeong et al. (2000); network science cocitation, Newman (2006); political blogs, Adamic and Glance (2005); Les Miserables word co-occurrence, Knuth (1993); high-energy theory collaborations, Newman (2001); NCAA football, Girvan and Newman (2002); USA power grid, Watts and Strogatz (1998); C. elegans neural network, Watts and Strogatz (1998); karate club, Zachary (1977); dolphins, Lusseau et al. (2003); Internet, Mark Newman, unpublished; macaque, Harriger et al. (2012); jazz musicians, Gleiser and Danon (2003); PGP, Boguñá et al. (2004); GDP, Frank and Asuncion (2010); GDP by country in present-day dollars, 1969–present, http://www.ers.usda.

Preliminary support for a modulatory or non-cell-autonomous function for new neurons comes from a study showing that ablation of adult-born hippocampal neurons results in an increase in gamma oscillatory activity suggestive of increased coordinated network activity in the DG (Lacefield et al., 2010). A second study

found a reduction selleck kinase inhibitor in inhibitory inputs to the DG following ablation of adult-born neurons (Singer et al., 2011). Analysis of mature granule cell activity and levels of inhibition in the DG of mice in which adult neurogenesis levels are manipulated is required to demonstrate that new neurons modulate the activity of mature granule cells to KRX-0401 mouse influence pattern separation. In addition to these proposed active roles for new neurons in pattern separation, neurogenesis may also influence encoding in other ways. For instance, the competition between new and old neurons for perforant path inputs (Toni et al., 2007) and potential postsynaptic targets may result in a redistribution of synaptic weights. Furthermore, a recent study showed that varying levels of neurogenesis

dictated the temporal extent of hippocampal dependence of memories (Kitamura et al., 2009). Thus, neurogenesis may ensure that an appropriate amount of space is available in the DG for encoding information by transferring memories out of the DG to the neocortex. Odor acuity is in part dependent on pattern separation in the olfactory bulb, and olfactory bulb pattern separation is modulated by, and dependent on, local inhibitory interneurons,

many of which are generated in adulthood. There are two populations of adult generated Isotretinoin interneurons in the olfactory bulb, juxtaglomerular neurons (periglomerular and short axon cells) and inhibitory granule cells (Lazarini and Lledo, 2011), that contribute to lateral inhibition and the spatiotemporal structure of olfactory bulb output activity. This inhibition helps enhance contrast between similar inputs (Luo and Katz, 2001, Schoppa and Urban, 2003 and Yokoi et al., 1995) and thus enhances separation between similar patterns of olfactory sensory neuron input (Figure 2). Prolonged odor exposure and odor conditioning not only induce a memory for the experienced odor, but also enhance acuity for that odor relative to other similar odors. This memory and enhanced olfactory acuity are associated with modified newborn granule cell survival (Moreno et al., 2009, Rochefort et al., 2002 and Rochefort and Lledo, 2005). In fact, given the spatial organization of odor-evoked activity across the olfactory bulb, cell survival is also spatially selective, with cells surviving primarily in the region activated by the exposure odor (Mandairon and Linster, 2009).

08). We also found IGF-1R inhibitor that the actual outcomes from a given target and hypothetical outcomes from the other targets were encoded independently in the DLPFC (Table 1). By contrast, OFC neurons tended to change

their activity similarly according to actual and hypothetical outcomes from different targets (χ2 test, p < 0.001). The fact that DLPFC activity related to the hypothetical outcomes was correlated only for the same target makes it unlikely that such effect arose simply from the visual responses of DLPFC neurons. This is because the geometric relationship between the positions of chosen and unchosen targets in trials used to estimate the activity changes related to hypothetical outcomes was identical,

except rotation, when they were compared for the same winning target and for the same choice of the animal (see Figure S5). We also tested whether the activity in DLPFC and OFC tends to change monotonically with hypothetical outcomes. To isolate the effect of hypothetical outcomes, this was tested separately for a set of trials in which the position of winning target as well as the animal’s choice and its actual outcome were fixed (2448 and 2412 cases for DLPFC and OFC, respectively; see Experimental Procedures). Among 215 and 219 cases showing significant effects of check details hypothetical outcomes in the DLPFC and OFC (1-way ANOVA, p < 0.05), respectively, the proportion of cases in which activity increased monotonically was 32.1% and 27.9%. This was significantly higher than the chance level (1/6) in both areas (binomial test, p < 0.001). We also found that the information about actual and hypothetical outcomes was processed with a similar time course in both cortical areas. In both areas, neurons

tended to display changes in their activity related to actual and hypothetical outcomes within approximately 200 ms from the feedback onset (e.g., Figure 3; Figure S3 and Supplemental Experimental Procedures). The time course of CPD related to the actual and hypothetical outcomes also peaked science almost simultaneously after the feedback onset (Figure 6). Moreover, we did not find any statistically significant differences in the latencies of neural activity related to actual and hypothetical outcomes for either cortical area, regardless of whether choice-dependent outcome effects were considered separately or not (Kolmogorov-Smirnov test, p > 0.3; Table S4). Consistent with the previous findings (Wallis and Miller, 2003), the latencies for the signals related to actual outcomes in the OFC were significantly shorter than in the DLPFC (p < 0.05), whereas the latencies for the signals related to hypothetical was not significantly different for the two areas (p > 0.7).

Using this SCN coupling assay, we found that SCN neurons are coupled by both VIP and GABAA signaling, and that these SCN factors operate in a cooperative or antagonistic manner depending on the state of the network. Male PER2::LUC mice (Yoo et al., 2004) were bred and raised under a 24 hr light:dark cycle with 12 hr light and 12 hr darkness (LD12:12). At 7–9 weeks of age, the mice either remained under LD12:12 or were transferred to a long-day-length condition

with 20 hr of light (LD20:4). As expected, LD20:4 produced a rapid decrease in the duration of the nocturnal active phase (Figure 1A; Figures S1A and S1B available online). In addition, LD20:4 mice displayed a stable phase angle of entrainment and free-running rhythms that derived from the predicted phase (Figures

A-1210477 cell line 1C and S1A), both of which are measures of true entrainment. Lastly, LD20:4 decreased the free-running period by ∼30 min (Figure S1D), similar to previous Smad inhibitor results obtained in this species (Pittendrigh and Daan, 1976a). Collectively, these results indicate that PER2::LUC mice entrain to this long-day-length condition. To investigate photoperiodic changes in pacemaker organization, coronal SCN slices were collected from PER2::LUC mice held under LD12:12 or LD20:4 (Figure 1B). Real-time bioluminescence imaging of PER2::LUC expression was conducted

in vitro and SCN spatiotemporal organization was mapped (see Experimental Procedures). Consistent with previous work (Evans et al., 2011), SCN slices from LD12:12 mice showed regional PER2::LUC peak time differences ranging from 2 to 4 hr on the first Bay 11-7085 cycle in vitro (Figures 1C and S1E; Movie S1). In contrast, LD20:4 slices displayed a much larger range of PER2::LUC peak times, with reorganization of two spatially distinct subpopulations (Figures 1C and S1E; Movie S2). In particular, LD20:4 slices were characterized by a central region that phase-led a surrounding semiconcentric region by ∼6 hr on the first cycle in vitro (Figures 1C–1E, p < 0.0001). This organizational pattern resembles the functionally distinct SCN compartments that are often referred to as the “core” and “shell” (Abrahamson and Moore, 2001 and Antle et al., 2003). Indeed, the dense population of arginine vasopressin neurons that demarcates the SCN shell compartment was in spatial registry with the late-peaking shell-like region, but not the early-peaking core-like region (Figure 2). In addition to changing the spatiotemporal organization of the SCN network, LD20:4 increased the level of PER2::LUC expression within the central SCN on the first cycle in vitro (Figure 1F, p < 0.0001).

High-threshold neurons would be used for maintenance of persistent firing rates within the integrator, whereas low-threshold neurons might be used as readout neurons. Experimental tests of this threshold organization should be possible through targeted silencing of specific subsets of neurons, for example, using halorhodopsin in the optically transparent larval zebrafish preparation (Schoonheim et al., 2010). One of the most striking features

of these models is the difference between the functional and structural connectivities (Figure 8). As shown in Figure 2, the two sides of the circuit are connected by mutual inhibition, anatomically suggesting the presence of a “double negative” (disinhibitory) positive feedback loop. In most models with inhibition between two populations, such positive feedback loops generate persistent activity Selleckchem Bioactive Compound Library (Cannon et al., 1983, Machens et al., 2005, Sklavos and Moschovakis, 2002 and Song and Wang, 2005). By contrast, our results Z-VAD-FMK chemical structure suggest that the anatomical mutual inhibitory loop is functionally broken so that there is no disinhibitory feedback loop to sustain persistent activity. Rather, as suggested previously (Aksay et al., 2007 and Debowy and Baker, 2011), recurrent excitation generates persistent activity at high firing rates, and low firing rates are held stable primarily by feedforward inhibition that is driven by the

stable high rates of the opposing population. The dichotomy between functional and anatomical connectivity demonstrated here suggests how a deeper understanding of the link between cellular properties and behavior can be facilitated by combining modeling work with large-scale anatomical studies. Serial-section electron microscopy (Briggman and Denk, 2006 and Micheva and Smith, 2007) and automated image processing (Chklovskii

et al., 2010 and Jain et al., 2010) promise unprecedented opportunities for defining the anatomical connectivity of a circuit. However, much in the way that the human genome project MYO10 was successful in identifying genes but not directly informative of their functional roles, connectomics will provide only an identification of anatomical connections. An understanding of the functional connectome therefore will rely on a hybrid approach where data on neuronal responses are combined with high-resolution structural information. Importantly, we note that not all structural information is equally informative, as we showed that integrator function was highly dependent on the proper balance of interactions between high- and low-threshold neurons, but insensitive to random changes in the connections between cells with similar thresholds. Thus, biophysically realistic circuit models can help guide anatomists in determining which aspects of the connectivity are most important to measure.

, 1998). This is consistent with the strong activation of bistratified cells by simultaneous inputs from CA1 and CA3. The firing of bistratified cells (Klausberger et al., 2004) coupled to SWRs rarely dropped below 80 Hz, providing entrainment of the innervated small pyramidal cell dendrites in cooperation with PV+ basket cells that innervate the soma

and proximal dendrites (Lapray et al., 2012 and Varga et al., 2012). However, all O-LM cells were silent during at least some SWRs, and on average also decreased their firing, which indicates that some inhibitory PLX3397 molecular weight input, activated during SWRs, contributes to their silencing. The O-LM cells are known to be innervated by vasoactive intestinal polypeptide-expressing, GABAergic

interneuron-specific IS-III cells (Acsády et al., 1996 and Chamberland et al., 2010) and also receive septal GABAergic innervation (Gulyás et al., 1990), which participate ZD6474 chemical structure in their inhibition (Chamberland et al., 2010). Unfortunately, the activity patterns of neither of these GABAergic inputs are known in vivo. In any case, the withdrawal of GABA and SOM released by O-LM cells from the most distal dendrites in CA1 may enable the return input from the entorhinal cortex and a reverberation between CA1 and the entorhinal cortex during closely timed repeated ripples (Davidson et al., 2009). In the mouse, O-LM cells fired at higher rates in vitro during SWR-like bursts

in CA1 (Pangalos et al., 2013) and CA3 (Hájos et al., 2013) or during awake immobility in vivo (Varga et al., 2012). The difference between these reports and our results could be due to species differences, loss of some of the inhibitory circuits in vitro, and higher firing rates during SWRs in awake compared to sleep states. The O-LM cells reported here fired significantly more during awake-SWRs than during SWRs in sleep. During theta oscillations, the pyramidal cell input to O-LM and bistratified cells may account for the firing of both cell types maximally around the theta trough, when pyramidal cells fire at highest probability in CA1. This was also Glutathione peroxidase predicted from tetrode recordings of pyramidal layer interneurons (Czurkó et al., 2011). However, the two cell types differ in that bistratified, but not O-LM, cells (Kim et al., 2012) receive input from CA3. Moreover, septal cholinergic input selectively activates O-LM cells via nicotinic acetylcholine receptors in arousal (Leão et al., 2012 and Lovett-Barron et al., 2014). Both cell types are also likely to receive septal GABAergic innervation (Gulyás et al., 1990), which may include a population of PV-expressing medial septal neurons that discharge at the peak of theta in anesthetized rats (Borhegyi et al., 2004) and temporally lead hippocampal theta (Hangya et al., 2009).