8% ± 0.9%, D 3.8% ± 0.9%; temperature: wild-type L 36.13°C ± 0.02°C, D 37.44°C ± 0.10°C; Sox14gfp/gfp L 37.17°C ± 0.41°C, D 36.86°C ± 0.23°C; average ± Wnt inhibitor SEM). The onset of motor activity

and feeding in Sox14gfp/gfp mice is variable and fragmented; we therefore looked at the sharper onset in the period for core body temperature rhythm to measure the phase advance in the circadian rhythm of Sox14gfp/gfp mice (wild-type zeitgeber time [ZT] 11.8 [−0.2 hr advance], Sox14gfp/gfp ZT 9.3 [−2.7 hr advance]; median) ( Figure 7J). Overall motor activity is increased in Sox14gfp/gfp mice (approximately 2.5-fold), while there was no significant difference in either total length of feeding episodes (cumulative minutes per day: wild-type: 150.6 ± 10.0, Sox14gfp/gfp: 168.2 ± 5.9; average ± SEM) or average core body temperature (wild-type: 36.7°C ± 0.06°C, Sox14gfp/gfp: 36.9°C ± 0.2°C; average ± SEM). Notably, mutant mice display bouts of strong motor activity consistently localized around the time

of D to L transition. Yet, this increased activity is transient and does not change the otherwise independent onset of the 24 hr cycle. An important function of ipRGCs is to control the light-dependent suppression of motor activity (negative masking). In this behavioral response, mice in their active phase (during the dark period) display an almost immediate cessation of movement when exposed to bright light. Activity starts again as soon as darkness is reestablished. We used the light paradigm illustrated in Figure 8A, with aL stimulation starting 1 hr into the subjective night (ZT 13) and check details maintained for the following 2 hr. While control mice had an almost immediate cessation of movement upon aL stimulation, Sox14gfp/gfp mice maintained their activity levels almost unchanged throughout the 2 hr light pulse

(percentage of prepulse activity: wild-type: 12.8% ± 3.1%; Sox14gfp/gfp: DNA ligase 95.2% ± 14.8%; average ± SEM) ( Figure 8B). A peculiarity of Sox14gfp/gfp mice is the short-lasting increase in motor activity at each light transition (L to D and D to L). This is particularly evident in the aL stimulation but is also consistently displayed in the circadian recordings under LD conditions for motor activity and for core body temperature ( Figures 7E, 7I, S5A, and S5B). Induction of the PLR completes the set of most studied responses initiated by ipRGCs. We therefore set out to measure the PLR in Sox14gfp/gfp mice. In agreement with the lack of any observable anatomical and neurotransmitter phenotype in the OPN of the Sox14gfp/gfp mice, we find that, under the conditions tested, the PLR is unaffected (pupil contraction as percentage of prepulse area: wild-type 82.2% ± 2.8%; Sox14gfp/gfp 82.4% ± 2.7%; average ± SEM) ( Figure S4). In summary, our analysis of circadian outputs and light-dependent physiological responses indicates that Sox14gfp/gfp mice retain the ability to produce an endogenous rhythm (i.e.

For cAMP assays, cells were treated similar to the N2A proliferation assays; however, after 48 hr, cells were collected and cAMP levels were measured using a commercial kit (Promega). Immunoprecipation and western blot experiments were performed as described in Mao et al. (2009).

All images were acquired using a confocal Zeiss LSM 510 microscope. Images were further analyzed with Adobe Photoshop and ImageJ v1.42q. Statistical analysis was performed with the student’s t test. All bar graphs are plotted as mean ± SEM. We would like to thank Tsai lab members and Stanley Center members for helpful discussions. We would like to give a special thanks to Janice Kranz, Kimberly Chambert, Doug Ruderfer, Doug Barker, Jennifer Moran, and Edward M. Scolnick for their intellectual input and logistical support. check details L.-H.T. is an investigator of the Howard Hughes Medical Institute and the director of the neurobiology program at the Stanley Center for Psychiatric Research. K.K.S. is a recipient of the Human Frontiers Science Program Long-term fellowship and an NSERC postdoctoral

fellowship. Y.M. is a recipient of the National Alliance for Research on Schizophrenia and Depression Young Investigator Award. This work was partially supported by a NIH RO1 grant (MH091115) to L.-H.T. and a grant from the Stanley Center for Psychiatric Research to L.-H.T. “
“An abiding principle of brain organization holds that the precise synaptic connectivity of neuronal networks determines brain functions. Conversely, pathological disturbances of this neuronal and synaptic patterning may contribute to the symptomatology of many neurological and psychiatric illnesses. Farnesyltransferase click here Therefore, understanding molecular

mechanisms that regulate neuronal development and connectivity can generate insight into the processes that govern the functional integrity of the developing and adult brain. In the hippocampus of the adult mammalian brain, new neurons are continually generated from neural stem cells throughout the lifespan of the organism (Lledo et al., 2006, Ming and Song, 2005 and Zhao et al., 2008). Adult neurogenesis recapitulates the complete process of embryonic neuronal development, including proliferation and fate specification of neural progenitors, morphogenesis, axon and dendritic growth, migration, and synapse formation of neuronal progeny (Duan et al., 2008 and Ming and Song, 2011). Many signaling pathways play conserved roles during embryonic and adult neurogenesis and disruption of many of these same pathways have also been implicated in the etiology of psychiatric disorders (Harrison and Weinberger, 2005 and Kempermann et al., 2008). There is a growing body of evidence demonstrating a convergent effect of genetic mutations that both confer susceptibility to psychiatric diseases and result in dysregulation of neuronal development, supporting a neurodevelopmental origin of these diseases.

Perhaps of relevance is the finding that mice are protected from cervicovaginal challenge with HPV16 pseudovirions even if they have serum levels of VLP antibodies that are 500-fold lower than the minimum that can be detected in an in vitro neutralization assay [63]. This observation raises the possibility that detection of any vaccine-induced

serum antibodies in women using standard assays indicates levels that are well above the minimum needed for protection. Detection of selleck products neutralizing antibodies in vitro to a non-vaccine type has generally corresponded with partial protection against infection by that type in clinical trials [25]. Therefore, the above trial compared cross-reactive immune responses to HPV31 and HPV45 induced by Cervarix® and Gardasil®[64]. For both types, the two vaccines induced similar levels of neutralizing and VLP ELISA reactive antibodies. This is in contrast to Cervarix®’s apparently greater degree of cross-protection against HPV45 infection FK228 in the efficacy trials. One interpretation of this result is that cross-protection is not antibody mediated. However, cross-reactive responses were very low, generally less than 1% the responses to homologous

types. Therefore, it may be that the current serologic assays are simply not sufficiently accurate measures of cross-type protective antibody responses. Safety and immunogenicity bridging studies were critical in extending regulatory approval for the vaccines to pre- and early adolescent girls and boys. Gardasil® induced geometric else mean titers (GMTs) in 10–15 year old girls and boys that were 1.7–2.0 and 1.8–2.7-fold higher, respectively, than the titers induced in 16–23 year-old women, as measured by cLIA [65]. Similarly,

Cervarix® induced GMTs in 10–14 year old girls that were 2.1–2.5-fold higher than those induced in 15–25 year-old women, as measured by ELISA [66]. Titers were also higher in 10–18 year old boys [67]. Higher titer antibody responses in younger individuals are also generally seen in trials of other vaccines. The higher responses in children led to the comparison of two- and three-dose vaccination protocols. Two doses of Gardasil® in 9–13 year-old girls delivered at 0 and 6 months was judged non-inferior to three doses in 16–26 year old women delivered at 0, 2, and 6 months, as measured by peak titers in HPV16- and HPV18-specific vitro neutralization assays [68].

, 2007). These RNAi strategies lay a solid foundation for Htt-lowering therapies for HD. However, several lingering questions remain to be addressed. First, can such a therapy maintain its efficacy and safety profiles in situations requiring chronic administration, such as in the more slowly progressive

full-length mHtt mouse models? Second, are there alternative ways to deliver Htt-lowering therapy to broader brain regions and cell types beyond the striatum that may also contribute to symptoms check details of HD? A study in this issue of Neuron by Kordasiewicz et al. (2012) provides strong preclinical evidence to support the use of antisense oligonucleotides (ASOs) as an Htt-lowering therapeutic for HD. ASOs are single-stranded DNA oligonucleotides (usually 8–50 nucleotides) that target cellular mRNA transcripts via complementary base pairing. The resulting DNA/RNA duplex undergoes catalytic degradation of the RNA component by RNase H, an enzyme present in most mammalian cells. Importantly, the single-stranded ASO can be recycled to mediate

multiple rounds of selective mRNA degradation ( Figure 1A). The stability selleck screening library and potency of ASOs are due to the phosphorothioate backbone and 2′-O-methoxyethyl (MOE) deoxynucleotide (DNA) sugar modifications, with specificity conferred by bioinformatic analysis and cell-based screening to optimize target engagement while minimizing off-target toxicity (

Bennett and Swayze, 2010). A strength for ASOs as candidate therapeutic over agents is the safety profiles in human studies so far, with one approved drug in clinical use and another 35 in clinical development ( Bennett and Swayze, 2010). Indeed, one such clinical study is a phase I clinical trial of ASO-mediated lowering of mutant SOD1 in familial amyotrophic lateral sclerosis, based on the original preclinical study by Cleveland and colleagues ( Smith et al., 2006). To test ASO therapy in HD models, Kordasiewicz et al. (2012) first established drug-like properties for the Htt ASOs. In the BACHD model that expresses full-length human mHtt (Gray et al., 2008), a 2 week infusion of two separate ASOs into the right ventricle, one selectively targeting human and the other targeting both human and murine Htt, is sufficient to induce dose-dependent and selective reduction of Htt for up to 12 weeks, with Htt levels returning to baseline at 16 weeks. The stability and high potency of chemically modified ASOs probably contribute to the lengthy period of Htt lowering after transient ASO infusion. The second surprising finding from the pharmacokinetics study is the broad distribution of ASOs in many brain regions (e.g., cortex, striatum, thalamus, midbrain, and brainstem) from intraventricular ASO delivery.

To examine the degree of neurogenesis (Figure 6H), BrdU (100 mg/kg)

was injected into DG-A::TeTxLC-tau-lacZ and wild-type litters from P15 to P22 (8 days total of injection). Horizontal brain sections from P23 animals were stained with the anti-BrdU antibody as descried above. Mice were euthanized and perfused with 4% PFA/PBS. Their brains were dissected out and postfixed with 4% PFA/PBS for 1 hr at 4°C. One-hundred-micrometer thick horizontal sections were cut on a vibratome and stored in PBS. Sections were placed Abiraterone manufacturer in a drop of PBS on a 10 mm Petri dish and chloromethylbenzamido-DiI (CM-DiI; Invitrogen) coated Elvax (0.1 × 0.1 × 0.1 mm) was placed onto the hilar region of the sections and left for 2 hr at 25°C or for 16 hr at 4°C. After CM-DiI coated Elvax was removed from

the sections, the sections were fixed again with 4% PFA/PBS for 1 hr; blocked in BMS-907351 cell line 2% BSA, 2% goat serum, and 0.1% Triton X-100 in PBS for 1 hr; and incubated with the anti-β-gal antibody at 4°C for 16 hr. Anti-mouse IgG1 Alexa Fluor 488 was used as the secondary antibody. Stained sections were mounted on a slide with Prolong antifade reagent. Images were taken with an Olympus confocal microscope using a 40× lens. For quantification of lacZ staining, color images taken by a digital camera (E990 Nikon) with a dissecting microscope (Olympus) were converted to grayscale images and then inverted with ImageJ software (NIH). The average signal intensity in the stratum lucidum layer of CA3 was calculated with ImageJ.

The average signal intensity in the stratum radiatum of CA3 in the same section was calculated and subtracted as the background. For quantification of β-gal immunostaining with DG lines (Figure 5, Figure 6, and Figure 8), images were acquired on a BX61 microscope (Olympus) with a 20× objective lens using the same exposure time for each experiment. The intensity of staining in the hilar region of the hippocampus was analyzed with ImageJ software. The intensity in the neighboring area without stained axons (in the stratum radiatum of CA3) in the same section was calculated and subtracted as the background Oxygenase (see Figure S3B). Mice were anesthetized with ketamine/xylazine (60 mg/kg ketamine, 10 mg/kg xylazine) and placed in a hand-made frame, and their skulls were exposed. A hole was generated with a 26G needle (−1.2 mm from bregma, 1.0 mm lateral from the midline, and 1.5 mm ventral from the skull surface for EC::TeTxLC-tau-lacZ mice; −2 mm from bregma, 1.5 mm lateral from the midline, and 2 mm ventral from the skull surface for DG::TeTxLC-tau-lacZ mice) onto the left hemisphere. Optimal locations were determined by preliminary experiments with Trypan Blue injections. TTX (0.5 μl of 5 μM TTX in PBS) was injected every 24 hr from P9 to P12, P14, or P16 (4, 6, or 8 days total of injection) with a Hamilton syringe (75RN, 7762-03) mounted on a micromanipulator. To suppress neurogenesis, AraC was injected either i.c.v. or i.p.

When we assessed the DLS spike activity trial by trial, however, we found a nearly opposite result. In the DLS, there was a clear trial-level modulation of the bracketing pattern Ferroptosis targets in relation to the occurrence of deliberative movements.

The bracketing index was higher on single runs lacking a deliberation at the choice point (Figure 4A), most prominently during learning and late overtraining (Figure 4B). This modulation involved weaker levels of DLS spike activity at the start of the single runs in which a subsequent deliberation occurred (Figure 4C). Activity during the deliberation and turn itself was only moderately and nonsignificantly lower during such trials and thus did not solely account for the effect. By contrast, in the ILs, spike activity during individual trials was similar whether the runs contained or lacked a deliberation (Figures 4A and 4C), and whether units were considered as an ensemble or were divided based on

positive or negative task-bracketing scores. This contrast suggests that the task-bracketing pattern that forms in ILs ensembles covaried over sessions with states of habitual behavior in which the majority of runs were nondeliberative, whereas the relatively similar ensemble LBH589 concentration pattern in the DLS appeared stable over the time span of sessions but was modulated trial to trial, especially at run start (Figure 3E). The DLS task-bracketing activity was also influenced by the stage of behavioral training mafosfamide that the rats had reached, however, as the pattern emerged after initial learning, suggesting that the presence of the DLS ensemble pattern was a function of learning or experience as well as the automaticity in individual runs. Units recorded from tetrodes placed in the

deeper layers of the IL cortex responded differently from those in the upper layers (Figures 5 and 6). ILd units did not form a pattern marking particular phases of the task but, rather, showed a general increase in activity as ensembles in the superficial layers formed a task-bracketing pattern (Figures 6, S1, and S2). We evaluated these superficial and deep ensembles across the cortical depth in small sliding spatial windows starting from the white matter and moving to more superficially situated levels, with the windows adjusted to include an average of at least five units per session (ca. 0.1 mm steps) (Figure S1). Ensembles sampled from tetrodes placed within about 0.5–0.6 mm of the midline exhibited a task-bracketing activity. As the samples shifted farther lateral (deeper, >0.6 mm), this pattern gave way during overtraining to one in which activity was pronounced through most of the run period. Despite the strikingly different forms of ensemble patterning in the ILs and ILd, the changes in their activity patterns followed similar time courses.

The average precue activity of positive neurons was higher on large-reward trials (Figures 3A and 4C; see also Figure S1A, arrow), while the average activity of negative neurons was higher on small-reward trials (Figures 3B and S1B). It was as if the VP neurons predicted the reward value DNA Damage inhibitor of the current trial even before the reward cue was presented. The prediction was possible because we used a pseudorandom reward schedule in which four consecutive trials consisted of two large-reward and two small-reward

trials. Thus, the monkeys could predict a large reward with a high probability in the next trial after they obtained a small reward and vice versa (Bromberg-Martin et al., 2010b). To test this issue, we compared VP neurons’ activity during the precue period (Figure S2). Thirteen out of 25 negative neurons and 11 out of 67 positive neurons showed significant differences in precue activity in reward-predictive manners (p < 0.05, Mann-Whitney U test). These results are consistent with the hypothesis that the VP neurons predicted the reward value

of the current trial based on the reward history. Animal’s reward expectation is known to influence saccadic performance (Takikawa et al., 2002; Watanabe et al., 2003). We hypothesized that VP neurons regulate the initiation of saccades using the reward expectation-related information. As a first step to test this hypothesis, we examined whether the activity of VP neurons was correlated with saccadic performance (i.e., saccade latency and velocity). We focused on the VP neurons’ activity during the presaccade period because it could directly modulate the saccadic preparatory PD-0332991 price signals in the oculomotor system. The presaccadic activity of VP neurons should then be correlated with the saccadic performance as it changed across trials. More specifically, since the position-reward contingency was reversed relatively frequently in our task, both VP presaccadic neuronal activity and saccadic performance should also be reversed in similar time courses. The results were basically consistent with this prediction (Figure 5). the Following the reversal of the position-reward contingency,

both saccade latency (Figure 5A) and saccade velocity (Figure 5B) showed clear changes. There were two kinds of reversal: small-to-large reversal (the saccade which had been associated with a small reward was now associated with a large reward) and large-to-small reversal (the saccade which had been associated with a large reward was now associated with a small reward). The saccade latency decreased and the saccade velocity increased instantly after the small-to-large reversal. In contrast, the saccade latency increased and the saccade velocity decreased more slowly after the large-to-small reversal. The presaccadic activity of VP neurons also changed clearly following the reversal of the position-reward contingency (Figures 5C and 5D).

Research in E.Y.I.’s laboratory is supported by the NIH (R01NS035549) and NSF (FIBR 0623527). This work was funded by a European Research Council Starting Independent Researcher Grant to R.B. “
“Cortical GABAergic interneurons are generated in multiple progenitor zones of the subpallial (subcortical)

telencephalon, including the lateral, medial, and caudal ganglionic eminences (LGE, MGE, and CGE) (Anderson NLG919 et al., 1997a, Anderson et al., 2001, Butt et al., 2005, Fogarty et al., 2007, Marin and Rubenstein, 2003, Pleasure et al., 2000, Sussel et al., 1999 and Wonders and Anderson, 2006). The specification, differentiation, and migration of these cells are regulated by multiple transcription factors, including the Dlx1,2,5,6 and Lhx6 homeobox genes. The Dlx genes are critical for interneuron migration and differentiation. For example, mice lacking Dlx1/2 show a block in the migration of most cortical and hippocampal interneurons ( Anderson et al., 1997a and Pleasure et al.,

2000). Mice lacking Dlx1 show defects in dendrite-innervating interneurons ( Cobos et al., 2005), whereas mice lacking either Dlx5 or Dlx5/6 have defects in somal-innervating (parvalbumin+; PV+) interneurons ( Wang et al., 2010). Studies on transcriptional alterations in the Dlx1/2–/– mutants have begun to elucidate the molecular pathways that regulate interneuron development and

function ( Long et al., 2009a and Long et al., 2009b). We have discovered that the Dlx genes promote the expression of two chemokine receptors, CXCR4 and CXCR7 (RDC1; CMKOR1) ( Long et al., Y-27632 clinical trial 2009a, Long et al., 2009b and Wang et al., 2010). Furthermore, these receptors are also positively regulated by the Lhx6 transcription factor ( Zhao et al., 2008) that is essential for the differentiation of PV+ and somatostatin+ (SS+) interneurons Megestrol Acetate ( Liodis et al., 2007 and Zhao et al., 2008). CXCR4 and CXCR7 are seven-transmembrane receptors that bind CXCL12, a chemokine also known as Stromal-derived factor 1 (SDF1) (Balabanian et al., 2005 and Libert et al., 1991). CXCL12 binding to CXCR4 triggers Gαi protein-dependent signaling, whereas CXCl12 binding to CXCR7 does not activate Gαi signaling (Levoye et al., 2009 and Sierro et al., 2007). On the other hand, many lines of evidence indicate that CXCR7 has an important role in regulating cell signaling in culture and in vivo. In developing zebrafish, CXCR4 and CXCR7 are both implicated in regulating migration of primordial germ cells (PMGs) and the posterior lateral line primordium, in part through their differential expression patterns (Boldajipour et al., 2008, Dambly-Chaudiere et al., 2007 and Valentin et al., 2007). For instance, while CXCR4 is expressed in the germ cells, CXCR7 is expressed in adjacent cells.

We found that the latency for find more the evoked PVN-RVLM depolarization was significantly longer when a prominent afterhyperpolarizing

potential (AHP) following the evoked bursts of action potentials was observed in the paired EGFP-VP neuron (n = 9; Figure 6B1), compared to neurons in which AHPs were absent (n = 6; Figure 6B2), or those in which a depolarizing afterpotential (DAP) was observed instead (n = 3; Figure 6D) (p < 0.001; Figure 6E). Moreover, a significant correlation between the EGFP-VP AHP duration and the PVN-RVLM latency was found (Pearson r = 0.89; p < 0.0001). The mean latency in paired recordings in which AHPs in EGFP-VP neurons were absent was similar to that observed following photolysis of caged NMDA (p > 0.3; see above), in which AHPs were not observed. In contrast to the effect on latency, the magnitude of the PVN-RVLM response was independent of the presence or

duration of an AHP in the stimulated EGFP-VP neurons (data not shown). Finally, to determine whether astrocytes participate Lapatinib research buy as intermediaries in the neurosecretory-presympathetic crosstalk, experiments were repeated following functional ablation of astrocytes with the selective gliotoxin L-aminoadipic acid (L-AAA; 250 μM, 30–60 min) (McBean, 1994 and Xu et al., 2008). Under this condition, stimulation of EGFP-VP neurons still efficiently evoked an excitatory response in PVN-RVLM neurons (p < 0.001, n = 5; (Figures 6D and 6F). In a few cases (n = 4) in which both neurons were intracellularly labeled with fluorescent dyes, segments of dendrites from the paired neurons were found in close proximity (12.5 ± 3.1 μm) (Figures 6G1–6G3). Our results demonstrate that evoked dendritic peptide release from an individual VP neuron can diffuse locally to affect the activity of a neighboring presympathetic neuron. We then tested whether the

basal average activity of the neurosecretory VP population as a whole was sufficient to generate a tonic-diffusing peptide pool, to continuously modulate presympathetic neuronal activity. Blockade of V1a receptors per se resulted in membrane hyperpolarization and inhibition of firing activity in presympathetic Non-specific serine/threonine protein kinase neurons (p < 0.001 and p < 0.01, respectively, n = 14; Figures 7A and 7B), unveiling the presence of a diffusible, tonic pool of VP. Conversely, the firing activity of EGFP-VP neurons was not affected (baseline, 2.2 ± 0.6 Hz; V1a antagonist, 2.2 ± 0.7 Hz; n = 5). To test whether the strength of the diffusible pool was dependent on the degree of activity of the VP population, we performed manipulations that either increased or decreased VP neuronal activity. The VP tone was enhanced by increasing extracellular K+ concentration (8.0 mM K+), as indicated by a more pronounced effect of the V1a antagonist in this condition, compared to normal K+ ACSF (p < 0.01; Figure 7D). Conversely, in the presence of the κ opioid receptor agonist U-50488 (1 μM), known to strongly inhibit VP neuronal activity (p < 0.01; Figure S7A; see also Brown et al.

Consciousness and feelings are topics that are best studied in humans. Research on the neural basis of feelings in humans is in its infancy (Panksepp, 1998; 2005; Damasio, 2003, Damasio et al., 2000, Ochsner et al.,

2002, Barrett et al., 2007, Rudrauf et al., 2009, Critchley et al., 2004 and Pollatos et al., 2007). We will never know what an animal feels. But if we can find neural correlates of conscious feelings in humans (and distinguish them from correlates of unconscious emotional computations in survival circuits), and show that similar correlates exists in homologous brain regions in animals, then some basis for speculating about animal feelings and their nature would exist. While such speculations Docetaxel price would be empirically based, they would nevertheless remain speculations. There are many topics that need further

exploration in the study of emotional phenomena in the brain. The following list is meant to point out a few of the many examples and is not meant to be exhaustive. 1. The circuits underlying defense in rodents is fairly well characterized and provides a good starting point for further advancement. An important first step is elucidation of the exact relation Dolutegravir supplier between innate and learned defense circuits. Paradigms should be devised that directly compare circuits that are activated by innate and learned cues of the same sensory modality and that elicit similar behavioral defense responses (freezing, escape, attack, etc). Comparisons should proceed in stepwise fashion within a species, with variation in the stimulus and response modalities (though mundane, systematic studies are important). The survival circuit concept provides a conceptualization of an important set of phenomena that are often studied under the rubric of emotion—those phenomena that reflect circuits and functions that are conserved across mammals. Included are circuits responsible isothipendyl for defense, energy/nutrition management, fluid

balance, thermoregulation, and procreation, among others. With this approach, key phenomena relevant to the topic of emotion can be accounted for without assuming that the phenomena in question are fundamentally the same or even similar to the phenomena people refer to when they use emotion words to characterize subjective emotional feelings (like feeling afraid, angry, or sad). This approach shifts the focus away from questions about whether emotions that humans consciously experience (feel) are also present in other mammals, and toward questions about the extent to which circuits and corresponding functions that are relevant to the field of emotion and that are present in other mammals are also present in humans.