, 2010, Kessels and Malinow, 2009 and Malenka and http://www.selleckchem.com/products/nu7441.html Nicoll, 1999). To evaluate the role of glutamatergic input to AgRP and POMC neurons, and more specifically its plasticity as regulated by NMDARs, we generated mice lacking NMDARs on either AgRP or POMC neurons. We accomplished this by crossing either Agrp-ires-Cre knockin mice ( Tong et al., 2008) or Pomc-Cre BAC transgenic mice ( Balthasar et al., 2004) with mice bearing loxed alleles of the Grin1 gene ( Tsien et al., 1996a).

Grin1 encodes NR1, a required subunit of the NMDAR. Consequently, deletion of Grin1 causes total loss of NMDAR activity ( Tsien et al., 1996b). Through such efforts, we have found that NMDARs on AgRP neurons, but not POMC neurons, play a critical role in controlling energy

balance. Consistent with this, AgRP neurons, but not POMC neurons, have abundant dendritic spines, the postsynaptic specializations where most excitatory synapses reside and within which NMDARs operate to control plasticity ( Bito, 2010, Higley and Sabatini, 2008 and Yuste, 2010). Finally, fasting-mediated activation of AgRP neurons, which serves to promote food-seeking behavior and conservation www.selleckchem.com/products/Temsirolimus.html of energy ( Aponte et al., 2011 and Krashes et al., 2011), is associated with markedly increased glutamatergic input, paralleled by and likely secondary to, at least in part, dendritic spinogenesis. Remarkably, the fasting-mediated increases in dendritic spines and glutamatergic neurotransmission, and the subsequent activation of AgRP neurons are all largely dependent upon the presence of postsynaptic NMDARs. Agrpires-Cre/+ knockin mice ( Tong et al., 2008) and Pomc-Cre BAC transgenic mice ( Balthasar et al., 2004) were crossed with lox-flanked Grin1 mice (Jackson Labs 005246) ( Tsien et al., 1996a) to disrupt NMDAR function in AgRP and POMC neurons. Control and Grin1-deleted study subjects were generated by mating Grin1lox/lox mice with either Agrpires-Cre/+, Grin1lox/lox mice or Pomc-Cre, Grin1lox/lox mice.

The littermate offspring from such matings are either controls (i.e., Grin1lox/lox mice) or lack Grin1 in AgRP (as in Agrpires-Cre/+, whatever Grin1lox/lox mice) or POMC (as in Pomc-Cre, Grin1lox/lox mice) neurons. Cre-mediated deletion during early embryogenesis, secondary to “subthreshold” expression of Cre during very early development, occurs for some loxed alleles with Agrp-Cre BAC transgenic mice ( Kaelin et al., 2004), and to a lesser degree with Agrpires-Cre knockin mice ( Tong et al., 2008). In the present study, early embryonic deletion of the Grin1lox allele was ruled out for all Agrpires-Cre/+, Grin1lox/lox study subjects (see Figure S1, available online, for details). In mice where brain slice electrophysiology was to be performed, Npy-hrGFP ( van den Pol et al., 2009) or Pomc-hrGFP ( Parton et al., 2007) BAC transgenes were crossed in for visualization of AgRP or POMC neurons.

The alternative mechanism, Compound Library high throughput ING, is solely based on the reciprocal interactions between inhibitory neurons. Basket cells are interconnected via reciprocal inhibitory synapses. Given the right physiological conditions, these synaptically

coupled networks of inhibitory neurons can generate fast synchronous oscillations (Van Vreeswijk et al., 1994). In this model, the entrainment of pyramidal cells to the oscillation is a natural consequence (since interneurons synapse onto pyramidal cells) but not a necessity for their generation. Several of the properties that characterize the interaction between excitation and inhibition in response to sensory stimuli are also found during beta and gamma oscillations (Figure 7). During hippocampal gamma oscillations for example, despite the fact that the magnitude of excitation and inhibition can vary on a cycle-by-cycle basis, Pictilisib cell line their overall ratio remains approximately constant (Figure 7A; Atallah and Scanziani, 2009). Furthermore, there is a phase difference between the excitatory and inhibitory components of the oscillation. During hippocampal gamma oscillations the inhibitory phase is delayed by 1–2 ms relative to the phase of excitation (Figure 7B;

Atallah and Scanziani, 2009). Similarly, inhibition has a lag of 5–10 ms relative to excitation during beta frequency oscillations (20–40 Hz) in olfactory cortex (Figures 7C and 7D; Poo and Isaacson, 2009). As a consequence, the ratio between excitation and inhibition, favors excitation early during these oscillation cycles while shifting toward inhibition later in the cycle. This sequence of excitation and inhibition leads to relatively narrow time windows for spiking, as is apparent in the tightly phase-locked firing behavior of pyramidal cells

relative to the oscillations in the hippocampus and olfactory cortex (Figures 7B and 7D; Atallah and Scanziani, 2009 and Poo and Isaacson, 2009). Does PING or ING predominate during physiological oscillations in the cortex? And what are the exact mechanisms that initiate and terminate oscillations? Do other interneurons beside basket cells contribute to cortical oscillations? Understanding the role of inhibition in cortical function has been a challenge, mainly due to the lack of sufficiently Cediranib (AZD2171) specific tools. The general pharmacological block of inhibition in cortical structures invariably leads to epileptiform activity and thus precludes an accurate assessment of which cortical properties (tuning, receptive field size, etc.) are affected by the absence of inhibition. Thus, many of the reported roles of inhibition rely on correlative evidence substantiated by a great deal of computational models. Despite the relative paucity of functional analysis, however, there has been an explosion in the number of studies reporting on the properties and mechanisms of cortical inhibition.

sp., but in males the total length/spicular length ratio is similar. The differences are the total length/posterior length, total length/cloacal tube ratios and the distance of the junction of cloacal tube and spicular tube from the posterior end of the body. In females, the differences appear in the rectum length and egg size. SEM has been used as a complementary tool for identification of different nematode species,

mainly to detect cuticular spines in the vulvar region and the spicular sheath, and to morphologically characterize bacillary bands. The bacillary band has been studied by scanning electron microscopy GSK1349572 nmr in 6 of the 12 Trichuris species that parasitize rodents ( Pfaffenberger and Best, 1989, Correa et al., 1992, Lanfredi et al., 1995, Robles et al., 2006 and Robles and Navone, 2006). The spineless vulvar opening is observed in all females of Trichuris in rodents studied by SEM, and only T. laevitestis has a protrusive vulva. The study of Barus et al. (1977), using SEM to compare the morphology and topography of spines on the spicular sheath, might help to solve some taxonomic problems regarding the Trichuris genus. For instance, it presents in detail how to compare spine morphology. But it does not show species of parasites that infect rodents. T. thrichomysi n. sp. has similar morphology, size and spine distribution

Crizotinib supplier as T. travassosi, but the spicular sheath is shorter. A pointed spine projection is observed in T. thrichomysi n. sp., T. travassosi, T. pardinasi, Trichuris leavitestis and Trichuris elatoris, but in Trichuris dipodomys the spines have a saccule-like projection. Adcloacal papillae are observed in T. thrichomysi n. sp., T. travassosi, T. pardinasi and T. leavitestis. The results here show

the contribution of scanning electron microscopy to reveal morphological details of copulatory organs and the bacillary band of Trichurids, contributing to the understanding of the functional role in parasite habits. Species of Trichuris have been described, but few pathogenicity studies have been reported ( Beck and Beverley-Burton, 1968). Chandler (1930) and Batte et al. (1977) reported, respectively, that camels and pigs infected with Trichuris spp. suffered from chronic diarrhea and dysentery for several weeks and the intestine contained much blood and mucus. Jenkins (1970) reported that damage to the intestinal crotamiton host cells was restricted only to slight cellular disruption and compression on the surface of mucosal cells in close proximity to the parasite niche, although the mucous membrane retained its normal appearance, and concluded that Trichuris suis is not a severe pathogen under natural conditions. In a histological and histochemical study of Trichuris vulpis in dogs, Fernandes and Saliba (1974) observed that the helminth does not cause great changes in the cecal wall, although they do cause intense congestion in the mucosa and submucosa. Tilney et al.

Thus, resensitization is unique to γ-4, -7, and -8 and appears to occur with RG-7204 all GluA subunit combinations. This kinetic phenotype

could result from mechanisms unrelated to an apparent “reversal” of desensitization. To evaluate these possibilities, we first performed experiments in the presence of cyclothiazide (CTZ), which blocks desensitization of all GluA-flip isoforms. Results showed that CTZ abolished the delayed current run up in GluA1 receptors conferred by coexpression of γ-8, suggesting that this phenomenon reflects a reversal in desensitization (Figures 2A and 2C). Further confirmation came from studies examining the effects of γ-8 on the mutant GluA1L497Y receptor, which does not show glutamate-evoked desensitization (Stern-Bach et al.,

1998). Consistent with the results found with CTZ, γ-8 expression did not produce the delayed increase in current when coexpressed with GluA1L497Y (Figures 2B and 2C). As previously published for γ-2 (Tomita et al., 2007b), γ-8 transfection did not significantly enhance glutamate-evoked currents from GluA1L497Y (Figure 2E). On the other hand, γ-8 increased the ratio of kainate/glutamate-evoked currents from GluA1L497Y, confirming association of γ-8 with this nondesensitizing receptor mutant (Figures 2D and 2F). These data show that the γ-8-mediated MLN2238 in vitro resensitization reflects reversal of desensitization in AMPA receptors. TARPs have a four transmembrane domain core and a cytoplasmic C-terminal tail, and alignment of the six TARP isoforms does not show unique homologies among γ-4, γ-7, and γ-8. To investigate which domains mediate resensitization, we generated three pairs of reciprocal chimeras that replaced in γ-2 and γ-8 the partner’s N terminus through second transmembrane domain whatever (NT-TM2), the third through fourth TM domain (TM3-TM4) and C-terminal domain, respectively. When cotransfected with GluA1, these six chimeras interacted with and produced functional AMPA receptors with large kainate-evoked currents, indicating coexpression of functional TARP proteins (Figure S2). Exchange of the C-terminal domains did not influence resensitization

for γ-8 or γ-2 (Figure S2, V-VI), whereas both the NT-TM2 and TM3-TM4 chimeras showed no resensitization for either the γ-8 or γ-2 host protein (Figure S2, I-II and III-IV, respectively). Thus, these results indicate that resensitization requires noncontinuous regions within the body of γ-8. Genetic studies have established that most AMPA receptor complexes in hippocampal neurons contain γ-8 (Fukaya et al., 2006 and Rouach et al., 2005). Consistent with previous studies, GYKI 53784-sensitive, hippocampal AMPA receptors showed no evidence of resensitization in response to glutamate (Figures 3A and 3C). Because AMPA receptors in γ-8 knockout mice have been shown to associate with γ-2 (Menuz et al., 2009 and Rouach et al.

The rostrocaudal positioning of motor columels maps onto anteroposterior coordinates of

limb muscle position; the ventrodorsal position of motor columels maps onto the proximodistal position of limb muscles; and the medial and Cabozantinib lateral positioning of columels maps onto the ventral and dorsal position of limb muscles. Additional functional distinctions, notably the emergence of α- and γ- as well as fast and slow subclasses, further diversify motor neurons that have been assigned to an individual pool (Friese et al., 2009 and Chakkalakal et al., 2010). Arguably, however, motor pools and columels represent the fundamental units of spinal motor organization in limbed vertebrates. Romanes’s pioneering studies effectively set the stage for the next sixty years

of work on the spinal Small molecule library cell line motor system—providing a structural framework for probing the developmental assembly of motor circuits and exploring the core logic of spinal motor function. In addition, the order uncovered by Romanes invited questions about the purpose of constructing such an elaborate and multilayered program of motor neuron positioning. The evolutionary conservation of spinal motor neuron patterns in higher vertebrates (Landmesser, 1978 and Ryan et al., 1998) emphasizes the importance of motor neuron positioning for motor circuit construction and movement, but its origins and significance have remained unclear. Several recent studies discussed below have begun to provide mechanistic information on the programming of motor pool position and to resolve why position matters during motor circuit assembly. Romanes’s early studies, and subsequent work by Landmesser, had shown that motor neurons cluster into coherent pools soon after motor axons enter the limb, raising the issue of whether the coincidence in timing of motor pool clustering and limb muscle innervation reflects a role for limb-derived signals in establishing motor neuron

settling position. Conversely, could motor neuron positioning be a factor in the precision of muscle target selection? Recent studies probing the developmental relationship between motor pool position and muscle innervation pattern have provided partial answers Rolziracetam to these questions. We now know that the specification of motor pool identity and position is initiated through a motor neuron transcriptional network that engages the actions of nearly two dozen vertebrate Hox proteins (Dasen and Jessell, 2009). The combinatorial expression of these homeodomain factors directs downstream molecular programs that impose motor pool character. Intriguingly, for some motor pools the expression of these downstream programs requires the convergent activity of limb-derived signals.

The steeper I-V relation observed in the absence of the GABAergic input should reduce the dynamic range of the ERG b-wave light responses in D1R−/− and GABACR−/− mice. Indeed, the rod-driven b-wave stimulus-response curves, both in the dark and at each background light intensity, obtained from both D1R−/− and GABACR−/− mice displayed a systematic ∼2-fold decrease in their dynamic range, defined as the range of intensities covering between 5% and

95% of the maximal response ( Figure 6), which served as a reason for decreased overall operational range, as illustrated NVP-AUY922 in Figures 1C, 2B, and 2D. Altogether, our results argue that GABACRs 3-MA ic50 mediate a tonic, sensitizing chloride current that hyperpolarizes WT rod DBCs and decreases their input resistance, thereby extending the amplitude and operational range of their depolarizing light responses. In

the final set of experiments, we aimed to identify the cellular source of the dopamine-dependent GABAergic input onto rod DBCs. Electrophysiological studies have described the most prevalent GABACR-mediated chloride currents in rod DBC axon terminals (e.g., Eggers and Lukasiewicz, 2006). However, their dendrites also display a distinct GABACR-mediated chloride conductance, documented in ferret (Shields et al., 2000), which is consistent with specific GABACR immunostaining of rod DBC dendrites and its absence in GABACR−/− rod DBCs ( McCall et al., 2002). Figure 7 shows that short GABA puffs evoked GABACR-mediated chloride currents in both the axonal and dendritic terminals of the same WT rod DBCs in the mouse. Complete suppression of GABA-dependent currents could only be achieved by blocking both GABAA and GABAC receptors. Interestingly, the relative Montelukast Sodium contributions of GABAAR- and GABACR-dependent currents were similar for dendrites and axon terminals ( Figures 7C and 7D). The latter finding is consistent with results obtained for rat ( Euler and Wässle, 1998)

and for mouse ( McCall et al., 2002) rod DBC axon terminals. Therefore, both axons and dendrites could be considered as potential sites of sustained GABAergic inputs. Furthermore, both axons and dendrites of rod DBCs are located postsynaptically to cells displaying strong immunostaining for D1R and GABA (amacrine and horizontal cells, respectively; Figure 1D and Figure S4). The expression pattern of KCC2 on both rod DBC axons and somas immediately adjacent to the relatively short dendrites (Figures 4C and 4D) predicts an efficient chloride extrusion over the whole length of the rod DBC and therefore does not favor either amacrine or horizontal cells as a major source of the GABAergic input.

This concerted focus means there will be opportunities not easily possible

in nongenetic systems to make novel connections between the details of PDF synthesis, release and signaling and other aspects of neuronal cell biology. In general we submit this peptide modulatory system has unique features because it combines the benefits of a genetic model system with the clarity of a neural network that displays cellular resolution. PDF expression is restricted to the CNS (Helfrich-Förster, 1997; Nässel et al., 1993): there Cabozantinib cost are ∼16 neurons that also display strong circadian clock protein expression—the large and small lateral neuron ventral (LNv). There are other PDF-expressing neurons in the CNS, but they are few in number and probably contribute little to the generation NVP-BKM120 supplier of rhythmic locomotor activity (Shafer and Taghert, 2009). In the circadian pacemaker network of the fly brain, ∼10% of the pacemakers (16 of ∼150) express PDF, whereas PDF-R is expressed by ∼60% of all pacemakers. Interestingly, PDF receptivity is found in nearly all

of the pacemaker cell groups (Shafer et al., 2008), but in most groups the PDF-R is only found in a subset (Im and Taghert, 2010)—for example, in the six-cell LNd pacemaker group, PDF-R is expressed by only three, and in the 15-cell DN1 group, PDF-R is expressed by only six to seven. An interesting aspect of the PDF cell population is the stark heterogeneity of its cellular properties. PDF expressing pacemakers are comprised of two groups—the 4–5 large LNv and the four small LNv (Helfrich-Förster, 1995). Both cell

types contribute (nonredundantly) to the generation of rhythmic locomotor activity (Cusumano et al., 2009; Helfrich-Förster, 1998; Shafer and Taghert, 2009; Sheeba et al., 2010; Yang and Sehgal, 2001). Both large and small LNv express the molecular clockworks, but they differ in many other important ways. (1) The large cells are neuromodulatory and form a large projection tangential to the retinotopic projections of axons from the eye, within a distal layer of the medulla (Helfrich-Förster, 1997; Taghert et al., Electron transport chain 2000). In contrast, the small LNv make a precise topographic projection to dorsal protocerebrum, for which incorrect targeting by even a few microns is enough to abrogate their informational functions (Helfrich-Förster, 1998). (2) Large cells express the bHLH transcription factor DIMM and give no evidence of utilizing a small classical cotransmitter (Taghert et al., 2001). DIMM-expressing neurons are dedicated and diverse neurosecretory cells that are generally large and that produce and episodically release large amounts of neuropeptides (Park and Taghert, 2009). Small LNv do not express DIMM and also cosecrete small conventional transmitters (Choi et al., 2012; Johard et al., 2009; Taghert et al., 2001; Yasuyama and Meinertzhagen, 2010).

They also found that the perceptual source memory task was associated with greater activity than the conceptual source memory task in a variety of regions, including parietal Entinostat nmr regions likely overlapping with those shown in Figure 2.

Although they did not distinguish between the attempt to retrieve conceptual or perceptual information and successful retrieval of this information—which the present results suggest can be critical—their findings are broadly consistent with the foregoing argument. Future experiments should directly test whether activity in the IPL is sensitive to the type of information being retrieved. The IPL tracks successful retrieval across a wide range of conditions. However, successful retrieval is not the only factor that affects IPL activity. For instance, violations of retrieval expectations also modulate IPL activity (O’Connor et al., 2010), but this finding does

not exclude the possibility that IPL plays a role in episodic memory. O’Connor et al. observed similar expectation violation effects in the hippocampus, which clearly plays a role in episodic Cabozantinib memory. However, the pattern of activity in IPL is complex and cannot be naively interpreted as a proxy for successful retrieval. Indeed, our observation that IPL activity is reduced when visual attention is engaged is further evidence that IPL activity is affected by factors other than successful retrieval. Our observations of functional dissociations between

dorsal and ventral regions of the lateral parietal cortex are consistent with recent formulations of the “attention to memory” model. According to this model, parietal systems associated with attention are not limited to the processing of perceptual information; these systems also play a role in orienting attention toward and maintaining attention on mnemonic representations (Wagner et al., 2005; Cabeza, 2008; Cabeza et al., 2008; Ciaramelli et al., 2008). Building on the dual system model of Corbetta and Shulman (2002), it has been proposed that the dorsal parietal cortex, including the IPS and superior Dipeptidyl peptidase parietal lobule, facilitates top-down attention toward perceptions and memories. The ventral parietal cortex (i.e., IPL) facilitates bottom-up attention toward perceptions and memories. According to the model, this ventral region serves as a “circuit breaker” that redirects attention toward new information that is task relevant or urgent ( Cabeza, 2008; Cabeza et al., 2008; Ciaramelli et al., 2008). The attention to memory model can account for the finding that the dorsal parietal cortex was more active during attempts to retrieve specific perceptual details because it proposes that the dorsal parietal cortex facilitates top-down, volitional orienting of visual attention as well as volitional attention toward specific mnemonic representations, such as stored visual details.

5]). Lysates were centrifuged at 16,000 × g for 10 min. The supernatants were retained for SDS-polyacrylamide gel electrophoresis. Protein samples were resolved with 4%–12% polyacrylamide gels, and subsequently electroblotted to polyvinylidene fluoride (PVDF) membranes. Blots Selleck Autophagy inhibitor were incubated with primary antibodies overnight at 4°C, followed by incubation with

HRP-linked secondary antibodies. Signals were visualized using ECL Plus reagent (GE Healthcare) and CL-XPosure Film (Thermo Scientific). The following primary antibodies were used: purified polyclonal rabbit anti-TMEM16B (1:500), mouse anti-α-tubulin (1:1,000, Sigma-Aldrich), mouse anti-β-tubulin (1:1,000, Covance), rabbit anti-DsRed (1:1,000, Clontech). The target sequences of TMEM16B-shRNA #2, 16B-shRNA #5 and scramble shRNA

are 5′- GCCTCCATCTTGTTTATGATT-3′ (clone TRCN0000127010, Open Biosystems), 5′- GCCAGTCATCTGTTTGACAAT-3′ (clone TRCN0000127013, Open Biosystems), and 5′- CCTAAGGTTAAGTCGCCCTCG-3′ (Addgene plasmid 1864) (Sarbassov et al., 2005), respectively. The shRNAs were cloned into pSicoR-GFP lentiviral transfer vector as described by Dr. Tyler Jacks laboratory (http://web.mit.edu/jacks-lab/protocols/pSico.html). Lentiviruses carrying the shRNAs were packaged and concentrated at the UCSF Sandler Center Lentiviral RNAi Core. Hippocampal cultures (105 cells at 4 DIV) were infected with lentiviruses expressing a scrambled shRNA, TMEM16B-shRNA #2 or #5. Tail current

and action potential MycoClean Mycoplasma Removal Kit recordings were performed and compared between GFP-expressing neurons 8–12 days after infection. Total selleck screening library RNA was extracted 10 days after infection for quantitative RT-PCR analysis. Whole-cell recordings were performed on individual cultured pyramidal neurons at 14–21 days in vitro. Pyramidal neurons were distinguishable by their relatively large size, lower input resistance (100–200 MΩ), and prominent apical dendrite. The recording pipettes were made from borosilicate glass capillaries (P-97 Sutter Instrument, 1.5 mm/0.86 mm) and pulled on the day of use (3–4 MΩ). All internal solutions have pH 7.2–7.4 and ∼300 mosm. All external solutions were made fresh the day of use and adjusted to pH 7.2–7.4 and ∼300 mosm (measured on the day of use). The bath was constantly perfused with fresh external solution at 2 ml/min throughout the recording, and all experiments were performed at room temperature. The neurons were visualized with a CCD camera (Hamamatsu). Recordings were amplified with MultiClamp 700B (Axon Instruments), and data were analyzed and plotted with Clampfit 10 and ORIGIN. See Supplemental Experimental Procedures for more details. Postnatal day 14–21 C57BL/6 mice were anesthetized with isoflurane and decapitated. Brains were removed and submerged in ice-cold sucrose cutting solution (mM): 50 NaCl, 2.

, 2011). The phase of slow EEG oscillations was estimated using either a wavelet transform (Morlet wavelets, frequency range: 1–16 Hz, PS-341 mouse four cycles per window) or a Hilbert transform applied to band-pass-filtered EEG signals in the delta band (1–4 Hz). While both methods provided time-resolved estimates of EEG phase at the single-trial level, the Hilbert transform did not make any assumption regarding the sinusoidal nature of narrow-band EEG signals. The spectral power of beta-band EEG

oscillations (>10 Hz) was estimated using a “multitapering” time-frequency transform (Mitra and Pesaran, 1999; Pesaran et al., 2002), as implemented in FieldTrip (Slepian tapers, frequency range: 5–40 Hz, five cycles and three tapers per window). The purpose of this multitapering approach is to obtain more precise power estimates by smoothing across frequencies. Note that both time-frequency transforms use a constant number of cycles across frequencies, hence a time window whose duration decreases inversely with increasing frequency. For simplicity, we report statistical tests on EEG data averaged across electrode sites. Occipital electrodes correspond to electrodes O1, Oz, and O2. Parietal electrodes correspond to electrodes P3, Pz, P4, and POz. Central/motor electrodes correspond to electrodes C3 and C4, analyzed as their

difference to calculate an interhemispheric asymmetry index. We regressed single-trial EEG signals PI3K inhibitor against several parametric quantities associated with individual elements at successive time samples following the onset of the corresponding element. These analyses were carried out separately for each of the eight elements in the stream, averaged across elements, and finally averaged across participants to produce a group-level grand average. For each element k, a general linear regression model was used in which we included the perceptual update PUk and the decision update DUk as two parametric regressors to predict the trial-to-trial variability in EEG signals at a given time t following element k. This parametric those regression was done separately at successive

times from 0 to 600 ms following element k. The time course of the corresponding parameter estimates—i.e., the normalized best-fitting regression coefficients, expressed in between-trial t units—measured the sensitivity of single-trial EEG signals to perceptual and decision updates. Because these time courses are time series of the between-trial correlation between the EEG and element k, we refer to them as describing the neural encoding of perceptual/decision updates provided by element k. Baselining for this regression-based analysis was performed by decorrelating the EEG signal at each electrode and each time following the onset of element k from trial-to-trial variability in the EEG signal at the last time sample before the onset of element k.