Vm SD for three different stimulus conditions is plotted as a function of simulated pairwise correlation between the LGN inputs in Figure S5C. At the correlation level measured in the LGN data (vertical dashed line, r = 0.25), the average values of peak Vm SDs for the model were comparable

to those obtained from intracellular recordings (1.32 mV versus 2.0 mV, 2.02 mV versus 2.6 mV, and 2.63 mV versus 3.8 mV for high-contrast null, high-contrast preferred, and low-contrast preferred stimuli). Changes in pairwise correlations between LGN inputs did not affect the increase in low-contrast preferred variability relative to high-contrast null variability: across all simulated values of pairwise correlations ranging from 0.05 to 0.70, low-contrast preferred variability Vismodegib solubility dmso was ∼120% more than high-contrast null variability (orange line in Figure S5C). For any excitatory Volasertib research buy synapse, the reversal potential (near 0 mV) dictates that a given increase in conductance starting from rest generates a much larger depolarization than

the same increase starting from a high baseline of synaptic input. We explored the effect of this saturating nonlinearity simply by removing it from model. In Figures 6G–6I, for example, where the relationship between LGN activity and Vm is assumed to be linear, the difference between low- and high-contrast Vm variability almost completely disappears, both at the preferred (G) and null orientations (H). Low-contrast preferred

stimuli, however, still evoked responses that were more variable than high-contrast null stimuli (I). The net effect of removing the conductance nonlinearity, then, is to remove the orientation-independence of Vm variability. Synaptic depression introduces a similar saturating relationship between the firing rate of LGN inputs and V1 membrane potential. Unlike the conductance Adenosine nonlinearity, however, when synaptic depression was removed from the model, only minor changes in Vm variability were observed (not shown)—compared to high-contrast stimuli, Vm SDs were 34% and 16% greater for preferred and null stimuli, and 88% greater for preferred low-contrast stimuli compared to null high-contrast stimuli. How these parameters interact in the model is diagrammed in Figure 7. Here again we highlight the responses at low and high contrast and preferred and null orientation (shaded rectangles in Figures 7B, 7D, 7F, and 7H). The first step of the model is to calculate the mean conductance change originating from the LGN, and its trial-to-trial variability, after taking the modulation of synaptic efficacy by synaptic depression into account. These are plotted (curves and error bars) for high and low contrast in Figures 7B and 7F, the curves showing the mean conductance change, and error bars showing variability.

Because negative affect and drug seeking

responses share common neural and molecular pathways, we next determined if p38α MAPK deletion in serotonergic neurons prevents stress-induced reinstatement DAPT cell line of drug seeking. First, we used immunohistochemistry to determine if SDS-induced increases in pp38-ir were prevented in the CKO mice. Consistent with previous results in this study, SDS did not cause an increase in pp38-ir in TPH-ir cells in p38αCKOSERT or p38αCKOePet mice (Figures 4A and S3J). In contrast, SDS increased pp38-ir in TPH-ir cells of p38αCKOGFAP mice, further supporting selective isolation of stress-induced p38α to serotonergic neurons (Figure S3J). Next we used a similar conditioning procedure as in Figure 1 to determine if serotonergic p38α MAPK deletion altered cocaine place preference. All groups showed similar levels of place preference for cocaine (Figure 4B), suggesting that deletion of serotonergic p38α does not alter either the associative learning required for place preference or the rewarding properties of cocaine. We then extinguished place preference over 3 days, and mice that met extinction criteria were see more socially defeated,

then tested in the place preference apparatus. We found that SDS caused reinstatement of cocaine place preference in both wild-type and control Mapk14Δ/+ mice, but stress-induced reinstatement was not evident in p38αCKOSERT or p38αCKOePet mice (t test, p < 0.05 versus matched control; Figure 4C). Finally, since cocaine injection (i.e., priming) is known to initiate reinstatement to drug seeking by distinct mechanisms ( Thomas et al., 2008 and Shaham and Hope, 2005), on the following day mice that did not reinstate to stress were injected with 15 mg/kg of cocaine and retested for place preference. All four groups of mice reinstated following a cocaine priming injection ( Figure 4D), suggesting that serotonergic p38α MAPK deletion selectively alters only stress-induced

modulation of drug-seeking. In conclusion, Rebamipide these results implicate serotonergic p38α MAPK in the regulation of affective state and show that selective deletion of p38α MAPK in serotonergic cells protects mice from stress-induced relapse of cocaine-seeking behaviors. To define the mechanism for the effects of p38α MAPK, we looked to studies in heterologous gene expression systems that previously suggested the plasma membrane serotonin transporter could be a p38 MAPK substrate (Zhu et al., 2005 and Samuvel et al., 2005). Building on in vitro data showing that p38 MAPK increases SERT activity, we first asked whether the serotonergic p38α-dependent CPA response was sensitive to the selective SERT reuptake inhibitor citalopram (Ravna et al., 2003). Mice were conditioned as previously described with a KOR agonist and then assayed for preference to the stressor-paired context. Control mice showed normal place aversion to the U50,488-paired compartment, whereas citalopram-pretreated mice (15 mg/kg, i.p.

We obtained four additional lines of evidence supporting the notion that CYSL-1 regulates the EGL-9 pathway as a cell-signaling mediator independently of its cysteine synthase activity. First,

the C. elegans genome does not appear to encode any homologs of O-serine acetyltransferase (SAT), which is an obligate component of the cysteine synthase pathway in bacteria and plants ( Mozzarelli et al., 2011 and Wirtz and see more Droux, 2005). BLASTP searches of animal protein databases against bacterial or plant SAT protein queries yielded only three significant hits (E value < 1e-30), in honey bees, Xenopus, and Caenorhabditis remanei, respectively. However, all three lack the invariant C-terminal isoleucine essential for binding to OASS ( Campanini et al., 2005, Francois et al., 2006 and Mozzarelli et al.,

2011), and no other Caenorhabditis species appeared in the search. Second, a potential Fasudil manufacturer bacterial source of OAS as a cysteine synthase substrate for CYSL-1 is unlikely, since feeding rhy-1(n5500) mutants on a cysE-deleted E. coli strain deficient in OAS synthesis did not rescue the rhy-1(n5500) phenotype ( Figure S6H). Third, we found that a lysine in an otherwise highly conserved motif crucial both for binding SATs and for functional CS activity ( Bonner et al., 2005) is a proline in CYSL-1 ( Figure S6G). Fourth, we found that CYSL-1 directly interacts with the C terminus of EGL-9 instead of forming a cysteine synthase complex via its active site, as shown and discussed below. In our rhy-1(n5500) suppressor screen, we isolated over three mutations (n5535, n5539, and n5552) that strongly suppressed K10H10.2::GFP expression and the defective O2-ON response ( Table 1A and Figure 6A). Linkage mapping placed n5535 on the right arm of chromosome V close to egl-9, which prompted us to determine the sequence of the egl-9 coding region of these mutants. We found that n5535 animals carry a missense mutation that converts the EGL-9 C-terminal sequence

EYYI to KYYI, while the n5539 and n5552 alleles alter a splicing donor and a splicing acceptor site, respectively, causing EGL-9 to be prematurely truncated near the EGL-9 C terminus without affecting the O2-sensing proline-hydroxylase domain ( Figure 6B). We noticed that the EYYI sequence of EGL-9 resembles the C-terminal SAT sequence DYVI, which penetrates into the active site of OASS, the CYSL-1 homolog in Arabidopsis ( Francois et al., 2006). These observations, together with the dominant nature of the n5535 phenotype and our epistasis analysis indicating that CYSL-1 inhibits EGL-9, suggested that n5535 might disrupt an EGL-9-interacting interface with CYSL-1 and in that way dominantly suppress rhy-1 LOF phenotypes. To test directly whether CYSL-1 binds to the EGL-9 C terminus, we generated a series of egl-9 mutant constructs and analyzed them in a yeast two-hydrid assay.

Phlebotomus species of sandflies breed in organic debris and feed mostly on plant juices but parous females need at least two vertebrate blood meals to permit egg maturation. Species vary in their degree of anthropophilia and MK0683 research buy hence transmission of leishmaniasis to humans. Leishmaniasis has been reported in SE Asia as an imported disease amongst those returning from residence in endemic areas ( Suttinont et al., 1987 and Suankratay et al., 2010). Cutaneous leishmaniasis has been reported from East Timor, the only record we are aware of from the Indonesian archipelago. However, clinical descriptions or laboratory

confirmation were not provided ( Chevalier et al., 2000). In 1999 visceral leishmaniasis was reported, for the first time in Thailand, in a 3-year-old girl living in Suratthani Province ( Thisyakorn et al., 1999). Apparent autochthonous transmission of visceral leishmaniasis has since been described in four additional patients from PD-1/PD-L1 inhibitor northern, central, and southern Thailand, but not in the northeast or elsewhere in SE Asia. As far as we are aware locally acquired cutaneous leishmaniasis has not been described from Thailand, only imported cases have been reported ( Viriyavejakul et al., 1997). Recently, leishmaniasis has been described in a human immunodeficiency virus infected Thai fisherman who presented

with nephrotic syndrome, fever, anemia, and thrombocytopenia. It seems most likely that he contracted the disease in Thailand although Indonesia is a remote possibility. Polymerase chain reaction and nucleotide sequence analysis of the internal transcribed spacer 1 of the small subunit ribosomal RNA

gene in blood and kidney biopsy specimens showed a putative new Leishmania species, of similar genotype to that described in a patient from southern Thailand with visceral leishmaniasis ( Suankratay et al., 2010). The ITS1 sequence of the rRNA gene suggested similarity to Leishmania brasiliensis and Leishmania guyanensis, which are the causative agents of New World visceral and cutaneous leishmaniasis, respectively. and Leishmania infantum, the cause of visceral leishmaniasis in the Mediterranean, western Asia and central China, was described in a patient in Bangkok ( Maharom et al., 2008). Phlebotomine sandflies are widely distributed in Thailand but collections in the villages of leishmaniasis patients yielded no known potential vector sandfly species of Leishmania. However, cow-biting and bat-biting cave-dwelling sandflies, vectors of Old World visceral leishmaniasis, have been described elsewhere in Thailand ( Apiwathnasorn et al., 1989). Positive direct agglutination tests (DAT) for Leishmania antibody have been reported from Thai cats and cows but there seem to have been no investigations of dogs as potential reservoirs apart from one investigation in Bangkok ( Sukmee et al., 2008).

Such studies will provide a genes-to-circuit-to-behavior integration, and also a place in the brain to look for behaviorally relevant regulatory effects. Although the initial acquisition of courtship memory, like olfactory memory, appears to occur in MB, through the activation of dopamine receptors in the MB γ neurons (Keleman et al., 2012; Qin et al., 2012), the site

of de novo gene expression underlying olfactory memory has recently been localized outside of MB (Chen et al., 2012). With courtship memory, GAL4-mediated overexpression of either Orb2A or Orb2B in MB neurons is sufficient to rescue the memory defect in orb2 mutants that lack the glutamine-rich domain ( Keleman et al., 2007). Therefore, to formally demonstrate that Orb2A-mediated oligomer formation and subsequent CPEB-dependent local translational regulation Temozolomide research buy are induced selleck kinase inhibitor selectively in MB γ neurons, it will be important to rescue the mutant alleles with Orb2A glutamine-rich domain and Orb2B RNA binding domain each restricted to γ neurons. Finally, the mechanistic details of local translation will likely involve other regulatory molecules,

some of which have already been implicated in memory and plasticity in Drosophila ( Barbee et al., 2006; Dubnau et al., 2003). A protein of particular interest is Pumilio, another RNA binding protein whose function is required for long-term olfactory aversive memory ( Dubnau et al., 2003) and which also contains an aggregation-prone prion-like domain ( Salazar et al., 2010). An understanding of the function of prion-like proteins in normal neuronal physiology will provide context to decipher the impact of pathological effects of aggregation prone prion-like proteins in neurodegenerative disorders. “
“The brain processes sensory information through the combined activity of large numbers of neurons. Until fairly recently, it was only possible to record from neurons one a time. These recordings have revealed much about sensory coding and enabled from scientists to hypothesize how larger neuronal

populations might represent sensory stimuli. Now that techniques such as two-photon imaging and multichannel electrophysiology allow hundreds of neurons to be recorded simultaneously, one can directly see how moderately sized neuronal populations actually operate. The brain, of course, works the same way however many neurons an experimenter manages to record from, so any population recording must be consistent with what was earlier seen at the single neuron level. Nevertheless, the results of population recordings often contradict hypotheses that had been inferred from single neuron studies. In this issue of Neuron, Bathellier et al. (2012) provide an excellent example of this, in a study of population coding in the superficial layers of mouse auditory cortex.

In Periodic sequences with deviant probability of 5%, the same sequences of 19 standards followed by a deviant would occur repeatedly, strengthening this habituation. Figures 7 and S2 strongly support this view, by showing that the responses to standards are larger on average in sequences with large variety of interdeviant intervals. Such a model requires the distribution of IDIs to be estimated and somehow stored. Torin 1 research buy Thus, this account suggests that detailed information about tone order of a sequence of 500 tones is stored and updated over a few minutes. Whether and how

such memory can be implemented remains an open question. On the other hand, the dependence of responses on the variety of IDIs demonstrated in Figure 7 may account for the complex pattern of responses as a function of deviant probability shown in Figure 4. The waiting time between successive deviants in our Random sequences is approximately geometrical, so that its SD is equal to the mean. Thus, for a deviant probability of 5%, the SD is 20,

while there are only 25 deviants in the sequence. In consequence, many different IDIs occur, presumably leading to the larger responses to standards in Random sequences than in Periodic sequences, which have a single value of IDI. On the other hand, when deviant OTX015 purchase probability is 20%, the average number of standards between successive deviants is 4, and the variability is much smaller. In consequence, the variety of IDIs is much more limited, and the contrast with the Periodic Calpain sequence, with a single IDI, is smaller, leading to smaller differences between the standard responses in the

two cases. The sensitivity to rather fine features of the order of tone presentations has possible implications to the processing of statistical regularities of the real world (see also Asari and Zador, 2009). Humans have language and music, both of which have complex structure that is crucial for accomplishing their effects. Animal calls may have “syntax” in that some sequences of calls are more probable than others (e.g., Holy and Guo, 2005). The sensitivity to order we describe here may be a mechanisms for reading out such syntactic regularities. In fact, human babies are sensitive to probabilistic rules that mimic some properties of languages (Marcus et al., 1999; Saffran et al., 1996); these results have been at least partially reproduced in rats (Toro and Trobalón, 2005). Our results suggest a neural correlate for such sensitivity. Furthermore, these results suggest that statistical information accumulated over very long durations influences neural activity as early as in primary auditory cortex. Thus, while the complexity of these sequences is obviously far below that of speech or music, the ability of rats to differentially encode Random and Periodic sequences may suggest the presence of the capabilities required to process such natural stimuli.

Nevertheless, our results argue against this model for the following reasons. First, a “switching model” in which a single spotlight travels in space predicts that it should be faster to switch attention between patterns that are close together than between patterns that are farther apart. We found the opposite (Figure 2 and Figure 3S). Second, our control experiment demonstrates an increase in RTs associated with changes

selleck in one translating RDP when its associated change probability is reduced and the change probability in the other pattern is increased. We argued that a switching spotlight should produce a RT distribution that approximates the pooled RTs distributions corresponding to both probabilities. However, we found that the pooled distribution has a higher mean than the one corresponding to 0.5-change probability targets of the main experiment.

In fact, the RTs distribution corresponding to targets with the largest change probability (0.8) was similar to the one corresponding to 0.5-change probability targets. This suggest that during the main experiment the animals devoted the same amount of attention to each target as to this website the 0.8-target of the control experiment, and that the level of attention to any of the RDPs never decreased to values similar or close to the one corresponding to the lowest (0.2) change probability target. For a switch model to account for these data animals had to switch attention between the 50-targets in ∼12 ms or less (determined by shortening the RTs corresponding to the 20-targets and repeating the pooling and comparison of RT distribution until it became nonsignificant). This is half of the estimated shift time

from our data and much shorter than the lowest value reported for stimulus driven Histamine H2 receptor (35 ms) and voluntary (∼200 ms) attention shifts in humans ( Horowitz et al., 2009). Third, and most importantly, we found that responses during tracking were decreased relative to those during attend-RF and attend-fixation when the translating stimuli circumvented the RF pattern. A switching spotlight of attention cannot account for these results. Instead, our findings suggest a relative suppression of responses to the RF pattern when it falls between the two attended RDPs. This strongly argues against models in which a single spotlight of attention travels in space, or rapidly turns on and off at the location of tracked objects ( Pylyshyn and Annan, 2006). This model proposes that when attending to multiple stimuli the spotlight of attention can split into multiple foci corresponding to each relevant stimulus and excluding distracters in between (Castiello and Umiltà, 1992, Cavanagh and Alvarez, 2005, Howe et al., 2010 and Niebergall et al., 2010). The animals’ behavioral performance in the main tracking task show that they attended to both translating RDPs.

, 2000). There are to date few studies of the role GDC-0199 purchase of V4 in figural completion behind occluders. However, one recent study compared responses of V4 neurons to real and “accidental”

contours (contours produced by the occluder which do not provide information about the true shape of the object) ( Bushnell et al., 2011a). This study found that responses to accidental contours were suppressed relative to real object contours, a suppression that disappeared with introduction of small gaps between the occluder and occluded objects. This suggests that V4 is an important stage in image segmentation. Cue Invariant Shapes ( Figure 6D). As objects typically can be defined by multiple features (e.g., color, motion, depth, contour), another important step in figure-ground segregation involves border-surface associations across multiple cues. As shown in Figure 6D, a square shape can be defined by luminance contrast, color, depth, or motion contrast

cues. Whether such invariance at mid-level processing stages is established by integration across multiple feature-specific input maps from V2 or via intra-V4 circuitry is unknown. Although the number of studies examining invariance in V4 is still limited, recent reports do support cue invariant shape coding in V4. Mysore et al. (2008) have described invariant V4 responses to shapes defined by either static or moving cues. In a study Sunitinib mouse by Handa et al. (2010), monkeys were trained on a cue dependent shape discrimination task (dependent on either a motion cue or luminance cue). About a third of the neurons in V4 responded selectively to a shape under ADP ribosylation factor both the motion and the luminance

cue conditions. Further studies are needed to support V4′s role in cue invariant shape recognition. Context Dependency ( Figure 6E). Central to the task of figure-ground segregation is the ability to modify what is perceived as figure and ground depending on situational cues such as stimulus context and attention. Indeed, there are numerous demonstrations of the ability of the visual system to modify the interpretation of what is figure and what is ground (e.g., the classic vase/face example where the figure is perceived as either a vase or as a pair of face profiles). That neuronal response in V4 is highly adaptable and modifiable will become particularly evident in the following section on attentional modulation. In particular, the role of top-down and bottom-up attentional influences on V4 activity has been a topic of intense investigation in the last two decades. However, only recently has the relationship between object representation and attention come into sharper focus. In the sections above, we have summarized studies on V4′s role in processing object features. There is also a vast literature on attentional effects in V4 (for reviews, Desimone and Duncan, 1995 and Chelazzi et al., 2011). Our purpose here is to try and draw ties between these two disparate bodies of literature.

We next examined whether depleting ApNRX also blocks the 5-HT-induced synaptic growth that accompanies LTF. Again, we found a significant decrease in the number of new presynaptic varicosities when presynaptic ApNRX was downregulated by the injection of antisense

oligonucleotides (Figures 6C and 6D; % increase in varicosity numbers: no injection –10.4 ± 4.8, n = 8; antisense alone –12.2 ± 3.8, n = 5; sense alone −6.8 ± 6.3, n = 4; 5-HT 35.2 ± 8.2, n = 13; 5-HT+antisense 0.6 ± 5.0, n = 17, p < 0.01 versus 5-HT; 5-HT+sense 36.8 ± 7.8, n = 9). We have hypothesized that the cytoplasmic tail of ApNRX is necessary to recruit new molecular components important for the learning-related SB203580 cell line assembly of the presynaptic active zone and its consequent 5-HT-induced remodeling and growth associated with LTF at the Aplysia sensory-to-motor

neuron synapse. To test this idea, we generated a C-terminal deletion construct of ApNRX (ApNRXΔC) that lacks the cytoplasmic tail. We expressed this construct in the sensory neurons and found that there was no obvious Entinostat research buy difference in the expression of ApNRXΔC-GFP compared to ApNRX-GFP (data not shown). To bring the expression level to a steady state, we waited two days after injecting ApNRX-GFP or ApNRXΔC-GFP into presynaptic sensory neurons and treated sensory-to-motor neuron cocultures with five pulses of 5 min of 5-HT (10 μM) and measured EPSPs before and 24 hr after 5-HT treatment. We found that the overexpression of ApNRXΔC in the presynaptic sensory neuron making functional connections with the postsynaptic motor neuron in culture leads to a significant reduction of LTF at 24 hr, but that overexpression of wild-type ApNRX did not enhance LTF ( Figure 6E;

% initial EPSP amplitude: 5-HT 70.4 ± 9.4, n = 51; 5-HT + ApNRXΔC overexpression 3.9 ± 5.6, n = 14, p < 0.001 versus 5-HT; 5-HT + ApNRX overexpression 71.8 ± 13.7, n = 10). Overexpression of wild-type ApNRX and or ApNRXΔC had no effect on basal transmission (% initial EPSP amplitude: no expression −12.2 ± 4.2, n = 28; ApNRXΔC overexpression alone –12.4 ± 11.6, n = 5; ApNRX overexpression alone −5.5 ± 13.2, n = 6). Unlike its effect on LTF, ApNRXΔC overexpression had no effect on STF induced by one pulse of 5-HT (10 μM) ( Figure 6F; % initial EPSP amplitude: no injection –8.5 ± 4.0, n = 19; ApNRXΔC overexpression alone 1.5 ± 5.7, n = 4; ApNRX overexpression alone 7.3 ± 12.8, n = 6; 5-HT 61.0 ± 7.3, n = 26; 5-HT + ApNRXΔC overexpression 77.0 ± 12.0, n = 9; 5-HT + ApNRX overexpression 78.9 ± 16.4, n = 11). These results with ApNRXΔC provide additional support for the notion that ApNRX is an important regulatory component of long-term memory storage in Aplysia perhaps via intracellular signaling cascades mediated by the cytoplasmic domain.

5 KCl, 1.3 MgCl2, 2 CaCl2, 1.25 KH2PO4, 11 glucose, and 26 NaHCO3 (pH 7.4, osmolarity 310) and allowed to recover for at least 1 hr in oxygenated ACSF at RT. The recording chamber was gravity fed with the same buffer. Hb neurons were visually identified with a microscope (Axioskop 2 FS plus) equipped with a digital camera (SPOT Insight). Patch electrodes were made from borosilicate glass (1B150F-4, World Precision Instruments, Inc.) with a microelectrode puller (P-97, Sutter Instrument,

CO). The internal pipette solution contained (in mM) 130 KCl, 2 MgCl2, 0.5 CaCl2, 5 EGTA, and 10 HEPES (pH 7.3, osmolarity 280; resistance, 5–7 MΩ). Typical series resistance was 15–30 MΩ. Nicotine was locally applied (50 ms, 8–10 psi) at different concentrations (1–600 μM) with a pressure device (PR-10, ALA Scientific Instruments) connected to a focal perfusion system (VM4, ALA Scientific GDC-0068 selleck kinase inhibitor Instruments) controlled with a trigger interface (TIB 14S, HEKA). The pipette was moved within 15–20 μm of the recorded cell with a motorized micromanipulator (LN mini 25, control system SM-5, Luigs & Neumann) for drug application and retracted after the end of the puff to minimize desensitization. In current clamp, the pipette with nicotine was positioned 100 μm from the cell and the drug was applied for 3 s. Neurons showing spontaneous oscillations

were not tested. Currents were recorded with a HEKA amplifier (EPC 10) using PatchMaster software (V2.20, HEKA), and were analyzed with FitMaster software (V2.3, HEKA). Membrane potential was held at −70 mV. Dose-response curves were calculated relative to the maximal response to nicotine (n = 3 cells per genotype). Adult brains were dissected and immediately embedded in O.C.T.

compound (Sakura). Frozen tissues were cut at the cryostat (20 μm coronal sections), thaw mounted much on ultrafrost microscope slides (Menzel Gläser), and stored at −80°C. For total [125I]-epibatidine binding sites, sections of WT and transgenic littermates (n = 3 per genotype) were incubated with 200 pM [125I]-epibatidine (NEN Perkin Elmer, Boston; specific activity 2200 Ci/mmole) in Tris 50 mM (pH 7.4) for 1 hr. For cytisine-resistant [125I]-epibatidine binding sites, sections were first incubated with 25 mM Cytisine (Sigma, St Louis) in Tris 50 mM (pH 7.4) for 30 min, as described previously (Zoli et al., 1995). Quantification of binding was done with ImageJ (NIH). WT (n = 5) and Tabac (n = 5) male mice were single housed in their home cages. Mice were provided with either nicotine or saccharin solutions as their sole source of fluid and bottles were weighed daily to measure nicotine intake. The volume of the drinking solution consumed per day was averaged for the period of consumption (3 days). Drinking solutions were: water, 2% saccharine in water (sweet water), 5 mM quinine (bitter water), or 100 μM nicotine in sweet water.