Adult (P60) ShhCreER/Shhfl mice and littermate Shhfl/+ controls were treated with tamoxifen for 5 days to induce deletion of the functional Shh allele. After a 2 week period to ensure loss of Shh protein expression and tamoxifen clearance, mice were given a 1 week pulse of BrdU, followed by a 3 week chase, to label newly produced interneurons in the OB. At the end of this time course, we observed a decrease in Shh protein in both the septum and ventral SVZ of ShhCreER/Shhfl mice ( Figures 4A–4D). Importantly, we also observed a loss of gli1 mRNA expression in tamoxifen-treated Dolutegravir clinical trial ShhCreER/Shhfl mice but not

treated Shhfl/+ controls, indicating that Shh pathway activity was GW786034 solubility dmso significantly decreased in ventral SVZ ( Figures 4E and 4F). As expected, the OBs of control animals had BrdU–labeled cells distributed throughout the granular layer, with 36% of cells observed in the deep granule layer ( Figures 4G and S5). Similar numbers of BrdU-labeled interneurons were present in all genotypes, and label-retaining cells as well as proliferating cells were present in the SVZ for both genotypes,

suggesting that stem cell self-renewal and progenitor proliferation were not grossly affected (data not shown). However, in ShhCreER/Shhfl animals, there was a shift in the distribution of labeled cells, with 15% fewer deep granule cells present and a 25% increase in superficial granule cells in the labeled population when compared to controls ( Figure 4G; p = 0.02, unpaired t test). This suggests that a subset of deep granule interneurons is lost when Shh ligand is removed from the adult brain. We also examined the effects of Shh loss unless on the population of calbindin (CalB)-positive

periglomerular cells normally produced by the ventral SVZ (Merkle et al., 2007). In ShhCreER/Shhfl animals, production of new CalB+ periglomerular cells (BrdU/CalB double-positive cells) was decreased by almost 90% compared to controls ( Figures 4H–4J; p = 0.0033, unpaired t test). This reduction in CalB-positive cells was more pronounced than the reduction in deep granule cells. Shh signaling may be required for the generation of specific subgroups of deep granule cells, but not others, resulting in a smaller decrease in the total population of deep granule cells. However, in both populations of cells, we observed a meaningful change in the cell types generated, indicating that Shh production plays a role in the production of different types of neurons destined for the OB by ventral NSCs. To test whether dorsal and ventral SVZ cells are equivalently responsive to Shh pathway activation, we administered Smoothened agonist (SAG) in the cerebrospinal fluid via an intracranial osmotic pump into the lateral ventricles. SAG is a small molecule that efficiently activates the Hh pathway (Chen et al., 2002).

, 2010)

and may be used for the control of insects and ticks. The southern cattle tick, Rhipicephalus (Boophilus) microplus, has been associated with losses in milk and beef production as well as damage to animal hides, which in turn have resulted in economic losses throughout the tropical and subtropical region where this tick is distributed ( Graf et al., 2004). The use of synthetic acaricidal products is the most common method for controlling southern cattle VE-822 research buy tick. However, the frequent use of these products in cattle herds may lead to contamination of milk and meat and fostering the selection of resistant ticks. In many countries, acaricide-resistant tick populations have increased to the point that few synthetic acaricides continue to have efficiency greater than 75% (Graf et al., 2004). Castrejón (2003) have previously

proposed the use of non-chemical control methods, including the use of plants with acaricide compounds, to reduce the environmental and financial impact CP 690550 of synthetic acaricides. In this context, phytochemicals may represent a useful tool for the control of ectoparasites and can also potentially be combined with other control strategies. Furthermore, phytochemicals may contribute to the production of milk and animal meat free of unsafe chemicals that are harmful to humans, animals, and the environment (Agnolin et al., 2010). Additionally, thymol and carvacrol are Generally Regarded As Safe (GRAS) ADAMTS5 food flavoring, which is an indication of low toxicity materials (United States Office of the Federal Register, 2009). The aim of the present study was to evaluate the activity of L. gracilis genotypes essential oil and their major components, carvacrol and thymol, to R. (B.) microplus larvae and engorged females. Leaves were collected from four L. gracilis genotypes ( Table 1) from the Active Germplasm Bank

(BAG) of Medicinal Plants at the Experimental Farm Rural Campus of the Federal University of Sergipe (UFS). Defoliation was performed manually, and leaves were dried in a forced air circulation oven at 40 °C for 5 days. R. (B.) microplus ticks used in the bioassays were bred and maintained at the Animal Science Department of the Federal University of Maranhão (UFMA). The essential oil was extracted by hydrodistillation in a Clevenger apparatus. Each sample consisted of 75 g of dried leaves harvested from three cloned plants, and samples were distilled for 140 min. The analysis of the essential oil chemical composition was performed using a gas chromatograph coupled to a mass spectrometer (GC–MS) (Shimadzu, model QP 5050A) equipped with an AOC-20i auto injector (Shimadzu) and a fused-silica capillary column (5% phenyl–95% dimethylpolysiloxane, 30 m × 0.25 mm i.d., 0.25 μm film, J&W Scientific). Helium was used as the carrier gas at a flow rate of 1.2 mL/min. The temperature program was as follows: 50 °C for 1.

, 2005), and kept in artificial cerebrospinal fluid in the dark to avoid ChR2 activation. Electrophysiological

Recordings. Whole-cell patch-clamp recordings were visually guided by infrared videomicroscopy (DM-LFS; Leica), using 4–9 MOhm borosilicate pipettes filled with 140 mM KCl, 10 mM HEPES, 2 mM MgCl2, 0.1 mM CaCl2, 0.1 mM BAPTA, 2 mM ATP Na salt, 0.3 mM GTP Na salt (pH 7.3), 300 mOsm, and amplified with an Axopatch 200B (Axon Instruments). For cell-attached recordings, KCl was replaced with KMeSO4. ChR2-mCherry expression was identified by fluorescent PD173074 microscopy and post hoc immunohistochemistry. Blue-Light Stimulation. For in vitro experiments, optical stimulation was done via a mercury lamp (Short Arc 103W/2, Osram; ∼5 mW/mm2) in combination with a shutter (VS25S22M1R1, Uniblitz) or a TTL-pulsed LED source (LXHL-LB3C, Roithner; ∼10 mW/mm2), both yielding similar results. Following recovery from guide cannulae implantation (1 week), female virgin rats of random hormonal cycle were exposed to a contextual fear-conditioning protocol. This consisted of three sessions

on consecutive days (Figure 5B). On day 1, rats were individually introduced in Panobinostat cost the conditioning box (45 × 18 × 25 cm) and after 10 min received a first series of seven electric shocks (0.8 mA) at random intervals (15–120 s) over 7 min. After the last these shock, the rats were left in the box for 3 more min. BL was applied in 10-ms pulses at 30 Hz via a glass fiber protruding 2 mm beyond the lower end of the cannulae and delivered light intensity of ∼10 mW. OTA injection was done via two injectors (cut to fit the 5.8 mm

guide cannulae protruding 2 mm beyond the lower end of the cannulae) that were bilaterally lowered into the guide cannulae, connected via polyten tubing to two Hamilton syringes that were placed in an infusion pump, and 0.5 μl of liquid containing 21 ng OTA was injected in each hemisphere at 0.25 μl/min over a 2 min period. Application of BL during Fear-Context Exposure. On day 2, the rats were habituated to the glass fibers by inserting them into the cannulae for the complete duration of the protocol, which was similar to the one of day 1 ( Figure 5C). On day 3, the rats were tested in the context for 10 min before receiving bilateral BL stimulation for either 20 s or 120 s. The effect was video recorded for the complete 20 min of the test (see Figure 5B). Freezing time was analyzed per 10 s intervals. Application of BL prior to Fear-Context Exposure. On day 2, rats received in addition a sham blue-light application during 6 min of very light isoflurane (5% induction, 1% for maintenance), during which time the glass fiber was inserted into the guide cannulae, as on day 3, without exposure to BL ( Figure 5D).

In addition to the cellular rearrangements that establish synaptic specificity check details among converging excitatory inputs, the signals which instruct these rearrangements are poorly understood. We previously found that glutamate release from BCs regulates the total number of synapses formed on retinal ganglion cell (RGC) dendrites (Kerschensteiner et al., 2009). Here, we test whether this

regulation depends on the afferent cell type and thus shapes the development of specific connectivity patterns. Twelve types of BCs relay different components of photoreceptor signals from the outer to the inner plexiform layer (IPL) of the retina (Wässle et al., 2009). As in many other parts of the nervous system, connections in the IPL are organized into laminar circuits (Sanes and Zipursky, 2010 and Wässle, 2004). Accordingly, axons of different BC types target distinct depths of the IPL where they innervate RGCs that stratify their dendrites at the same depth. Developing BCs elaborate axonal arbors from neuroepithelial-like precursor processes, extending side branches throughout the IPL of which they selectively stabilize those located at the correct depth (Morgan et al., 2006). BC axons attain

their final laminar position before the retina processes visual information and continue to form and eliminate synapses with RGC dendrites at high rates for more than a week after laminar targeting is complete (Kerschensteiner et al., 2009 and Morgan et al., 2008). How retinal circuits are rewired by this synaptic remodeling after laminar targeting remains Resminostat unknown. Combining different Epigenetics Compound Library chemical structure genetic labeling techniques and imaging

approaches we examined the development of synapses from three types of BCs with a single type of RGC in vivo. We find that the different BC axons initially connect equally to the shared RGC dendrite. Synaptic patterns of the different BC types diverge only after laminar targeting is complete. This is achieved by selective changes in the conversion of axo-dendritic appositions to synapses. Neurotransmission regulates this process in a cell type-dependent manner and thus shapes synaptic specificity among converging excitatory axons. To observe directly how different afferents establish specific patterns of connections with a common target, we fluorescently labeled pairs of neurons and their connections in the intact developing retina. Pairs consisted of one of three BC types and a single RGC type. Of the twelve BC types found in mice (Wässle et al., 2009) eleven receive input from cone photoreceptors and one from rods. Five cone BC types (B1, B2, B3a, B3b, B4) express ionotropic glutamate receptors on their dendrites and depolarize in response to light decrements (OFF BCs) (Haverkamp et al., 2001a and Haverkamp et al., 2001b).

e., highest to lowest) irrespective of which quadrant was occluded. In this way the worst category

included every rat’s lowest quadrant score. If each rat used a different local cue, the removal of that cue should have disrupted performance and scores should have been poor in the worst category. However, Figure 7B indicates that performance for both groups was well above chance in the worst category and greater than 70% correct (Figure 7B, rightmost data). These findings provide compelling evidence that the rats did not use local cues to solve the discrimination problem but rather solved the problem by making an object-level discrimination. We also tested the same rats on the NOR task, a standard task of recognition memory in the rodent (Clark and Squire, 2010 and Winters et al., 2008). Figure 8 shows the performance of both Anti-diabetic Compound high throughput screening groups. The perirhinal lesion group was impaired on a 24 hr delay. Thus, while the discrimination task and the associated perceptual probe trials did not reveal any hint of impairment, recognition memory was impaired. Impaired recognition memory is

the expected result in animals with perirhinal damage (e.g., Prusky et al., 2004, Kornecook et al., 1999, Mumby and Pinel, 1994, Buffalo et al., 1999, Nemanic et al., 2004, Bussey et al., 1999, Bussey et al., 2000, Ennaceur et al., 1996 and Winters and Bussey, 2005). Note though that the recognition memory impairment observed here was milder than has been typically reported. For example, rats with perirhinal lesions are typically buy AZD5363 impaired on delays as short as 15 min (e.g., Ennaceur et al., 1996 and Winters and Bussey, 2005), whereas our animals were intact on a delay of 3 hr and impaired only on the 24 hr delay. Differences in lesion size between studies are unlikely to account for the different findings because our lesions were as large as, or larger, than those in previous studies (Ennaceur et al., 1996 and Winters and Bussey, 2005). It may be significant that the rats in our study had far more

testing experience (i.e., thousands of training trials over several months in the discrimination task) and were tested for recognition memory much longer after perirhinal lesions (i.e., 6–9 months rather than a few weeks) than in any previous study of perirhinal Olopatadine lesions in rats. Perhaps one of these factors (or a combination of these factors) might be important. In any case, the main finding was that our lesions were sufficient to impair recognition memory. Our finding of intact performance on feature-ambiguous discriminations after perirhinal lesions contrasts with prior work in the monkey. In monkeys, impairments were observed on discriminations that involved stimuli with high-feature overlap and that required complex object-level perception (Buckley and Gaffan, 1998, Buckley et al., 2001, Bussey et al., 2002 and Bussey et al., 2003).

The objective was to test if sustained excitatory synaptic input to

a target neuron changed its intrinsic excitability. This is distinct from short-term depression of synaptic responses observed following Ipatasertib short periods of conditioning spontaneous activity (Hennig et al., 2008 and Hermann et al., 2007) in that our studies focused on how sustained synaptic inputs can influence postsynaptic voltage-gated conductances rather than synaptic strength. The conditioning synaptic stimulation lasted 1 hr and consisted of evoked EPSPs at a mean frequency of 10 Hz (with interstimulus intervals [ISIs] generated by a Poisson process, giving a total of 34,875 stimuli/1 hr). We stimulated the trapezoid body calyceal projection to the MNTB or mossy fiber/commissural projections (which were DCG-IV insensitive; see Figure S1C available online) to CA3 pyramidal neurons. Stimulation

at 10 Hz induces neither LTP nor LTD (Dudek and Bear, 1992) and provided a sustainable stimulation rate that did not deplete transmission to subthreshold levels (Figure S1A, stimulus recordings at 55 min) and was comparable with physiological firing rates for the MNTB (Kopp-Scheinpflug ATM inhibitor et al., 2003) and hippocampus (Fenton and Muller, 1998 and Klyachko and Stevens, 2006). In naive slices under current clamp recording, evoked EPSP trains at moderate frequencies securely triggered APs in principal neurons of the MNTB (<400 Hz). The illustrated example in Figure 1 shows single AP responses to each presynaptic stimulus at a frequency of 100 Hz (Figure 1A, Naive, upper black). But transmission failure occurred rapidly at 800 Hz or above (Figure 1A, Naive, lower black), consistent with previous reports (Taschenberger and von Gersdorff, 2000).

After synaptic conditioning (post-conditioning, PC: 1 hr stimuli), the response of MNTB neurons to moderate frequency stimuli was robust and unchanged (Figure 1A, upper red trace; 100 Hz, PC), but high-frequency stimuli now triggered APs with greater reliability (Figure 1A, PC, lower red trace; 800 Hz). The conditioning reduced evoked synaptic currents (Figure S1B), consistent with nitrergic suppression of AMPARs reported previously (Steinert et al., 2008). Comparison of the mean output (MNTB APs) to input (at Edoxaban 100, 800, or 1000 Hz) for naive (Figure 1B, black bars) and PC slices (red bars) showed increased reliability of transmission for high-frequency stimulation after conditioning. The synaptic conditioning also increased AP threshold (Figure 1C), consistent with reduced postsynaptic excitability. AMPAR and NMDAR antagonists (50 μM AP-5, 10 μM MK801, 10 μM CNQX applied for the 1 hr conditioning period) blocked these changes, whereas perfusion of NO donors (NO: sodium nitroprusside, SNP or PapaNONOate, each 100 μM for 1 hr) mimicked the threshold increase (Figure 1D).

The above analysis implicitly assumes that the minimum of the cost function over the allowed range of weights corresponds to a local minimum, so that the first derivative is zero and the second derivatives characterize deviations from the minimum. However, because Dale’s law constrains

the weights to be strictly nonnegative or nonpositive, the best-fit parameters can occur on the boundary of the permitted set of weights. In such cases, we also VE-822 chemical structure computed the gradient of the cost function to determine the direction of greatest sensitivity to infinitesimal changes in weights. However, for changes in weights large enough to lead to noticeable mistuning, the increase in the cost function due to linear changes along the gradient direction were much smaller than the quadratic changes determined by the sensitivity matrix (Figure S6G). In addition, because the gradient vector reflected weights that were prevented by Dale’s law from changing signs, its direction corresponded to increasing magnitudes of all zero-valued weights and therefore overlapped with eigenvector 2. Thus, for the circuits analyzed here, the gradient provided little additional information beyond that provided by the sensitivity matrix. This work was supported by NSF grant IIS-1208218-0 (M.S.G., E.R.F.A.), NIH grant

R01 MH069726 (M.S.G.), a Sloan Foundation Research C646 Fellowship (M.S.G.), a Burroughs Wellcome Collaborative Research Travel Grant (M.S.G.), a UC Davis Ophthalmology Research to Prevent Blindness grant (M.S.G.), a Wellesley College Brachmann-Hoffman Fellowship (M.S.G.), a Burroughs Wellcome Career Award at the Scientific Interface (E.R.F.A.), and the Searle Scholars program (E.R.F.A.). We thank Guy Major, Jennifer Raymond, Sukbin Lim, Andrew Miri, Brian Mulloney, Michael Wright, Melanie Lee, and Jochen Ditterich Methisazone for helpful comments on this work and Melanie Lee for computational assistance. “
“We choose between objects based on their values, which we learn from past experience with rewarding consequences (Awh et al., 2012 and Chelazzi et al., 2013).

The values of some objects change flexibly, and we have to search valuable objects based on their consequent outcome (Barto, 1994, Dayan and Balleine, 2002, Padoa-Schioppa, 2011 and Rolls, 2000). On the other hand, the values of some other objects remain unchanged, and we have to choose the valuable objects based on the long-term memory. Since the stable value formed by repetitive experiences is reliable, we may consistently choose the object regardless of the outcome (Ashby et al., 2010, Balleine and Dickinson, 1998, Graybiel, 2008, Mishikin et al., 1984 and Wood and Neal, 2007). Both flexible and stable value-guided behaviors are critical to choose the valuable objects efficiently. If we rely only on flexible values, we would always have to make an effort to find valuable objects by trial and error.

Contrastingly, another found blunted HR responses to psychosocial

stress in adults with a FH of alcoholism as compared to those with a negative FH (Sorocco et al., 2006). Clearly, more research is needed to elucidate this relationship. Furthermore, as almost all of the above-mentioned studies were performed in adults, little is known about the relation between HR and substance use in adolescents. Substance use can be viewed as a manifestation of externalizing problems (e.g., symptoms of oppositional defiant and conduct disorder; Krueger et al., 2002 and Liu et al., 2009). The relation between externalizing problems and HR has been well established; low resting HR is the best-replicated SRT1720 correlate of antisocial behavior in children and adolescents,

and FG-4592 ic50 attenuated HR in response to a stressor is also well-confirmed (Ortiz and Raine, 2004). Thus, literature on the relation between externalizing problems and HR may provide insight into the relation that could be found between substance use during adolescence and HR reactivity, i.e., low resting HR and attenuated HR response to stress. Of interest here is whether HR is related to externalizing problems in general, or whether it is related specifically to substance use. The goal of this study was to examine the relation between adolescent alcohol and tobacco use and HR (re)activity during a psychosocial stressor. We expected to find that adolescents who drank more alcohol and adolescents who used more tobacco would portray low resting HR and an attenuated HR response to the stressor. By entering number of externalizing problems into the model, we aimed to examine whether any found relation is specific for alcohol and tobacco use. Physiological responses are generally postulated to reflect subjective, or perceived stress (PS), responses (Thayer, 1970), however, convincing experimental evidence of this is limited Idoxuridine (Oldehinkel et al., 2011). Therefore, a second aim of this study was to examine whether HR and PS were related, and whether alcohol and tobacco use were

related to PS. Based on findings in earlier studies in which HR did but PS responses did not vary by risk group (e.g., Fairchild et al., 2008 and Finn and Pihl, 1987), we hypothesized that HR would be related to PS, but that PS would not be related to alcohol and tobacco use in adolescents. The current sample of 275 14–20-year-old (M = 17.22; SD = 1.31) adolescents is part of a larger sample that participated in the South Holland 2 study, a large Dutch general population study of youth aged 6–20 years. For this larger study, children and adolescents were randomly drawn from registers of 35 representative municipalities in the Dutch province of South Holland including both urban and rural areas. At the second assessment wave, 536 individuals were eligible for the present study on the adolescent group, being between the ages of 14 and 20.

To assess the statistical accuracy of the measured gain value, we applied bootstrap method (Carandini et al., 1997 and Efron and Tibshirani, 1993) for each cell. The measured gain value matched closely to the mean of bootstrapped gain values, deviating from it by no more than 2% (Figures S2E–S2G). In addition, the variation of bootstrapped gain values was small, mostly less than 10% (Figure S2H). This analysis supports the statistical accuracy of the measured gain values. Consistent with the notion of a scaling of contralateral spike responses, the binaural TRF exhibited

the same CF (Figure 3F) and a similar bandwidth (Figure 3G) as that of the contralateral TRF. With multiple linear regression (see Experimental Procedures), we statistically determined on a single-cell basis that there was no significant contribution (p > 0.05) http://www.selleckchem.com/Caspase.html from the ipsilateral spike response to the binaural spike response in 123 out ABT-888 of 131 recorded neurons (104 from anesthetized, and 27 from awake animals) and that there was no significant thresholding effect (p > 0.05; see Experimental Procedures) in 127 out of 131 neurons (the p values for the other cells are larger than 0.01). In contrast, the contralateral response was found to be highly significantly correlated with the binaural response (p < 10−15) in all the 131 neurons. Together, these results further suggest that binaural spike responses can be best described as a scaling up/down of contralateral spike

responses, with the ipsilateral ear input providing the gain control. How is the ipsilateral input-mediated gain control achieved? To further understand binaural integration at the synaptic level, we recorded excitatory and inhibitory synaptic TRFs to both monaural and binaural stimulation. As shown by

an example cell in Figure 4A, the cell received stronger excitatory inputs driven contralaterally than ipsilaterally, whereas its inhibitory inputs driven contralaterally and ipsilaterally in large part had similar amplitudes. From the synaptic amplitudes, it is clear that the binaural synaptic response was neither a subtraction nor a summation between the contralateral and ipsilateral responses. Similar to the analysis of spiking responses, we plotted the binaural synaptic amplitude against the contralateral below synaptic amplitude to the same tone stimulus (Figure 4B). The correlation coefficient was high for both the excitatory and inhibitory synaptic responses, indicating a strong linear relationship. The slope of linear fitting was 0.81 for excitation, but 0.98 for inhibition. This indicates that the binaural excitatory input was significantly scaled down from the contralateral excitatory input, whereas the binaural inhibitory input was not very different from its contralateral counterpart. A second example cell is shown in Figures S3A and S3B. As summarized for 11 similarly recorded cells, the linear correlation between binaural and contralateral synaptic responses was strong, with the r mostly larger than 0.

In agreement with recent work (Lindén et al., 2011, Pettersen et al., 2008 and Schomburg et al., buy GSK1120212 2012), we find that the LFP length scale depends on the temporal coordination of the oscillatory inputs. Importantly, spiking and spike-related currents impact the LFP not only in the higher bandwidths but also in lower ones (<50 Hz) traditionally thought to reflect purely postsynaptic activity. We found that L4 pyramids impacted the LFP and CSD within both layers, with their extracellular contribution greatly affected by the presence or absence of active membranes. Conversely, L5 pyramids with their large somata, thick apical dendrites, and strong synaptic input contribute not

only to the LFP within L5 but also to the LFP in L4, especially at the onset of coordinated synaptic input. Given their large size and powerful synaptic

input, it is conceivable that L5 pyramids could also contribute to the LFP in other layers, such as L2/3 or L6, not simulated here. Thus, whereas the LFP reflects processing of neurons whose cell bodies are situated within that layer, the extended nature of pyramidal neurons gives rise to multipoles that reach into nearby layers. Importantly, we found this to be broadly true in simulations exhibiting varying see more degrees of input correlation. In agreement with others (Pettersen et al., 2008 and Schomburg et al., 2012), we find that L4/5 basket cells with their fairly low density (compared to excitatory neurons), localized and symmetric dendritic arbor, spatially uniform synaptic Liothyronine Sodium input, the small temporal width of their somatic spikes, and lack of strong afterpotentials have only a small impact on the LFP and CSD, even though their spike frequency is substantially higher than that of their excitatory neighbors (Figure 3C). Of course, this does not suggest that extracellular action potentials from individual basket cells are small. When considering LFP characteristics, such as amplitude and spatiotemporal width, we observed that these are markedly shaped by the impinging

pattern of postsynaptic currents and membrane characteristics. Increasing model complexity from only postsynaptic to using fully reconstructed active neurons attenuates the LFP amplitude, alters its spatiotemporal width and changes the sink-source location. Additionally, our findings regarding the LFP length scale (depending on input correlation, approximately 200–600 μm along the cortical depth and 100–300 μm tangentially) points to the necessity of large-scale models to study the origin and functionality of the LFP. How do these observations compare with LFPs recorded during whisker stimulation (Riera et al., 2012)? Such stimulation triggers prominent thalamocortical input into L4 in somatosensory cortex (Brecht and Sakmann, 2002).