Inhibitory Cues Research Articles

Expression of Developmentally Important Axon Guidance Cues in the Adult Optic Chiasm.

PurposeRegeneration of optic nerve axons after injury can be facilitated by several approaches, but misguidance at the optic chiasm is often observed. We characterized guidance cues in the embryonic visual system and adult optic chiasm before and after optic nerve crush (ONC) injury to better understand barriers to optic nerve regeneration in adults.MethodsRadial glial (RC2/BLBP/Slit1), developmental (Pax2) and extracellular markers (CSPG: H2B/CS-56) were assessed in C57BL/6J mice by immunohistochemistry. RC2, BLBP, Slit1, and CSPG are known inhibitory guidance cues while Pax2 is a permissive guidance cue.ResultsAt embryonic day 15.5 (E.15.5), RC2 and BLBP were identified superior to, and extending through, the optic chiasm. The optic chiasm was BLBP−ve in adult uninjured mice but BLBP+ve in adult mice 10 days after ONC injury. The reverse was true for RC2. Both BLBP and RC2 were absent in adult mice 6 weeks post-ONC. Slit1 was present in the optic chiasm midline and optic tracts in embryonic samples but was absent in uninjured adult tissue. Slit1 was observed superior to and at the midline of the optic chiasm 10 days post-ONC but absent 6 weeks after injury. Pax2 was expressed at the junction between the optic nerve and optic chiasm in embryonic brain tissue. In embryonic sections, CS-56 was observed at the junction between the optic chiasm and optic tract, and immediately superior to the optic chiasm. Both 2H6 and CS-56 staining was absent in uninjured and ONC-injured adult brains.ConclusionDifferences in guidance cue expression during development, in adulthood and after injury may contribute to misguidance of regenerating RGC axons in the adult optic chiasm.

Facets of externalizing psychopathology in relation to inhibitory control and error processing

A prominent characteristic of externalizing psychopathology is the inability to suppress or modulate behavioral responses and impulses. These tendencies have been associated with cognitive indicators of inhibitory control (P3) and error processing (error-related negativity [ERN] and positivity [Pe]). However, the extent to which these trait-like components are characteristic of specific manifestations, or externalizing proneness more generally, remains unclear. Our study aimed to further contextualize externalizing behaviors by examining associations between distinct facets of externalizing symptoms and relevant behavioral phenotypes (substance use, aggression, pathological personality and internalizing symptoms) as well as electrophysiological and behavioral indices of inhibitory control (congruence and no-go P3, flanker interference, commission errors) and error processing (ERN and Pe, post-error slowing). Using a sample of community and jail dwelling offenders (N = 497), we used Confirmatory Factor Analyses to estimate a general externalizing factor (EXT), representing shared variance, and latent factors representing symptoms related to callous-aggression (CAL; conduct disorder and antisocial personality disorder) and alcohol and drug dependence (AD and DD). Additionally, a subset of participants (N = 89) had their brain activity recorded during a flanker task. Factor analyses supported general EXT and CAL factors; however, unique AD/DD overlapped highly with shared EXT, suggesting that DSM substance use symptoms in our study reflect more general problems with disconstraint/impulsivity rather than variance specific to substances. The general EXT was marked by behavioral correlates of impulsivity and negative affect, and laboratory task deficits in error monitoring, but with greater differential processing of inhibitory cues. The CAL specific factor was associated with affective shallowness phenotype, and, interestingly, laboratory measures of enhanced processing of inhibitory cues and error adjustment. This research has implications for understanding neurocognitive processes associated with distinct manifestations of disordered behavioral inhibition.

Multi-compartment Microfluidic Device Geometry and Covalently Bound Poly-D-Lysine Influence Neuronal Maturation.

Multi-compartment microfluidic devices have become valuable tools for experimental neuroscientists, improving the organization of neurons and access to their distinct subcellular microenvironments for measurements and manipulations. While murine neurons are extensively used within these devices, there is a growing need to culture and maintain human neurons differentiated from stem cells within multi-compartment devices. Human neuron cultures have different metabolic demands and require longer culture times to achieve synaptic maturation. We tested different channel heights (100 μm, 400 μm, and open) to determine whether greater exposure to media for nutrient exchange might improve long-term growth of NIH-approved H9 embryonic stem cells differentiated into glutamatergic neurons. Our data showed an opposite result with both closed channel configurations having greater synaptic maturation compared to the open compartment configuration. These data suggest that restricted microenvironments surrounding neurons improve growth and maturation of neurons. We next tested whether covalently bound poly-D-lysine (PDL) might improve growth and maturation of these neurons as somata tend to cluster together on PDL adsorbed surfaces after long culture periods (>30 days). We found that covalently bound PDL greatly improved the differentiation and maturation of stem cell-derived neurons within the devices. Lastly, experimental paradigms using the multi-compartment platform show that axons of human stem cell derived neurons intrinsically regenerate in the absence of inhibitory cues and that isolated axons form presynaptic terminals when presented with synaptic targets.

Alternate day fasting decreases preference for a calorically dense diet by increasing chow intake and altering meal pattern parameters

Alternate day fasting (ADF) is an effective dietary strategy for weight loss in both humans and rats. However, fasting can elicit hyperphagia in rats, particularly upon access to a calorically dense, high-energy (HE) diet. To examine the effects of ADF on HE diet preference, male and female Sprague-Dawley rats were randomly assigned to receive either ad-libitum or alternate day access to both chow and HE food. Meal pattern analysis was conducted to provide a more detailed explanation of changes in HE preference. ADF rats had a decreased preference for the HE diet compared to controls. Both male and female ADF rats increased in overall intake of chow. However, for male ADF rats, the decrease in HE preference was driven by an increase in both size and number of chow meals; for females, it was driven only by an increase in number of chow meals. Meal size is controlled by both positive feedback (e.g., from the oral cavity) and negative feedback (e.g., from postoral inhibitory signals). Thus, for males, fasting appeared to increase orosensory stimulation and/or decrease sensitivity to inhibitory cues towards chow. For females, fasting appeared to decrease sensitivity to inhibitory cues towards chow. The decrease in HE preference observed in the current study may contribute to the effectiveness of ADF as a dietary strategy for weight loss.

The effects of a GLP-1 analog liraglutide on reward value and the learned inhibition of appetitive behavior in male and female rats.

Liraglutide, a relatively long-lasting analogue of glucagon-like peptide-1 (GLP-1), has received recent attention as a treatment for obesity. It has been proposed that activation of GLP-1 receptors in mesolimbic reward pathways contributes to this outcome by reducing hedonic value of food. However, other findings suggest that activation of GLP-1 signaling pathways may suppress appetitive behavior by enhancing a hippocampal-dependent form of learned inhibition. The present experiment compares these two alternatives. Rats first solved a hippocampal-dependent discrimination problem in which a target stimulus signaled the delivery of sucrose, except when it was preceded by an inhibitory cue that signaled nonreward. The effects of 12 daily intraperitoneal (i.p.) injections of liraglutide on responding to the target cue was then compared with and without the inhibitory stimulus. Relative to saline, liraglutide suppressed responding to the target cue only on trials when the inhibitory stimulus was also present (p<.05). This outcome was independent of sex and maintenance diet (Western diet or standard chow). The failure of liraglutide to suppress responding in the absence of the inhibitory cue argues against the notion that this GLP-1 agonist reduced the value of food reward and favors the idea that it enhanced a hippocampal-dependent form of behavioral inhibition.

Evolution of a central neural circuit underlies Drosophila mate preferences.

Courtship rituals serve to reinforce reproductive barriers between closely related species. Drosophila melanogaster and D. simulans exhibit reproductive isolation due, in part, to the fact that D. melanogaster females produce 7,11-heptacosadiene (7,11-HD), a pheromone that promotes courtship in D. melanogaster males but suppresses courtship in D. simulans males. Here we compare pheromone-processing pathways in D. melanogaster and D. simulans males to define how these sister species endow 7,11-HD with the opposite behavioral valence to underlie species discrimination. We show that males of both species detect 7,11-HD using the homologous peripheral sensory neurons but this signal is differentially propagated to the P1 neurons that control courtship behavior. A change in the balance of excitation and inhibition onto courtship-promoting neurons transforms an excitatory pheromonal cue in D. melanogaster into an inhibitory cue in D. simulans. Our results reveal how species-specific pheromone responses can emerge from conservation of peripheral detection mechanisms and diversification of central circuitry and illustrate how flexible nodes in neural circuits can contribute to behavioral evolution.

A Drosophila In Vivo Injury Model for Studying Neuroregeneration in the Peripheral and Central Nervous System.

The regrowth capacity of damaged neurons governs neuroregeneration and functional recovery after nervous system trauma. Over the past few decades, various intrinsic and extrinsic inhibitory factors involved in the restriction of axon regeneration have been identified. However, simply removing these inhibitory cues is insufficient for successful regeneration, indicating the existence of additional regulatory machinery. Drosophila melanogaster, the fruit fly, shares evolutionarily conserved genes and signaling pathways with vertebrates, including humans. Combining the powerful genetic toolbox of flies with two-photon laser axotomy/dendriotomy, we describe here the Drosophila sensory neuron - dendritic arborization (da) neuron injury model as a platform for systematically screening for novel regeneration regulators. Briefly, this paradigm includes a) the preparation of larvae, b) lesion induction to dendrite(s) or axon(s) using a two-photon laser, c) live confocal imaging post-injury and d) data analysis. Our model enables highly reproducible injury of single labeled neurons, axons, and dendrites of well-defined neuronal subtypes, in both the peripheral and central nervous system.

Hunger, taste, and normative cues in predictions about food intake

Normative eating cues (portion size, social factors) have a powerful impact on people's food intake, but people often fail to acknowledge the influence of these cues, instead explaining their food intake in terms of internal (hunger) or sensory (taste) cues. This study examined whether the same biases apply when making predictions about how much food a person would eat. Participants (n = 364) read a series of vignettes describing an eating scenario and predicted how much food the target person would eat in each situation. Some scenarios consisted of a single eating cue (hunger, taste, or a normative cue) that would be expected to increase intake (e.g., high hunger) or decrease intake (e.g., a companion who eats very little). Other scenarios combined two cues that were in conflict with one another (e.g., high hunger + a companion who eats very little). In the cue-conflict scenarios involving an inhibitory internal/sensory cue (e.g., low hunger) with an augmenting normative cue (e.g., a companion who eats a lot), participants predicted a low level of food intake, suggesting a bias toward the internal/sensory cue. For scenarios involving an augmenting internal/sensory cue (e.g., high hunger) and an inhibitory normative cue (e.g., a companion who eats very little), participants predicted an intermediate level of food intake, suggesting that they were influenced by both the internal/sensory and normative cue. Overall, predictions about food intake tend to reflect a general bias toward internal/sensory cues, but also include normative cues when those cues are inhibitory. If people are systematically biased toward internal, sensory, and inhibitory cues, then they may underestimate how much food they or other people will eat in many situations, particularly when normative cues promoting eating are present.

Set-Congruent Priming Stimuli Normalize the Information Processing of Psychopathic Offenders

Psychopathic individuals display characteristic deficits in processing emotion cues, the abstract meaning of words, and peripheral inhibitory cues, that have been linked to deficits in self-regulation and antisocial behavior. One view, supported by recent research, is that psychopathic individuals have difficulty processing set-incongruent information and that their difficulty may be ameliorated using task manipulations that establish a set-relevant focus of attention. We evaluated this characterization of the psychopathic deficit using a lexical decision (i.e., word recognition) task and priming manipulation that caused target stimuli to be set-congruent or set-incongruent. As predicted, low-anxious (i.e., primary) psychopathic participants displayed a significantly greater priming effect than low anxious non-psychopathic participants. The results highlight the potential value of priming relevant cognitive sets to overcome the costly information processing deficits associated with psychopathy. Treatment efforts emphasizing a balance of attention between primary and peripheral information may prove especially effective for reducing maladaptive behavior in psychopathic individuals.

Combined chondroitinase and KLF7 expression reduce net retraction of sensory and CST axons from sites of spinal injury

Axon regeneration in the central nervous system is limited both by inhibitory extracellular cues and by an intrinsically low capacity for axon growth in some CNS populations. Chondroitin sulfate proteoglycans (CSPGs) are well-studied inhibitors of axon growth in the CNS, and degradation of CSPGs by chondroitinase has been shown to improve the extension of injured axons. Alternatively, axon growth can be improved by targeting the neuron-intrinsic growth capacity through forced expression of regeneration-associated transcription factors. For example, a transcriptionally active chimera of Krüppel-like Factor 7 (KLF7) and a VP16 domain improves axon growth when expressed in corticospinal tract neurons. Here we tested the hypothesis that combined expression of chondroitinase and VP16-KLF7 would lead to further improvements in axon growth after spinal injury. Chondroitinase was expressed by viral transduction of cells in the spinal cord, while VP16-KLF7 was virally expressed in sensory neurons of the dorsal root ganglia or corticospinal tract (CST) neurons. After transection of the dorsal columns, both chondroitinase and VP16-KLF7 increased the proximity of severed sensory axons to the injury site. Similarly, after complete crush injuries, VP16-KLF7 expression increased the approach of CST axons to the injury site. In neither paradigm however, did single or combined treatment with chondroitinase or VP16-KLF7 enable regenerative growth distal to the injury. These results substantiate a role for CSPG inhibition and low KLF7 activity in determining the net retraction of axons from sites of spinal injury, while suggesting that additional factors act to limit a full regenerative response.

The expression of chemorepulsive guidance receptors and the regenerative abilities of spinal-projecting neurons after spinal cord injury

Spinal cord injury (SCI) in mammals leads to permanent loss of function because axons do not regenerate in the central nervous system (CNS). To date, treatments based on neutralizing inhibitory environmental cues, such as the myelin-associated growth inhibitors and chondroitin sulfate proteoglycans, or on adding neurotrophic factors, have had limited success in enhancing regeneration. Published studies suggested that multiple axon guidance cues (repulsive guidance molecule (RGM) family, semaphorins, ephrins, and netrins) persist in adult animals, and that their expression is upregulated after CNS injury. Moreover, many adult CNS neurons continue to express axon guidance receptors. We used the advantages of the lamprey CNS to test the hypotheses that the regenerative abilities of spinal-projecting neurons depend upon their expression of chemorepulsive guidance receptors. After complete spinal transection, lampreys recover behaviorally, and injured axons grow selectively in their correct paths. However, the large identified reticulospinal (RS) neurons in the lamprey brain are heterogeneous in their regenerative abilities – some are high regeneration capacity neurons (probability of axon regeneration >50%), others are low regeneration capacity neurons (<30%). Here we report that the RGM receptor Neogenin is expressed preferentially in the low regeneration capacity RS neurons that regenerate poorly, and that downregulation of Neogenin by morpholino antisense oligonucleotides enhances regeneration of RS axons after SCI. Moreover, lamprey CNS neurons co-express multiple guidance receptors (Neogenin, UNC5 and PlexinA), suggesting that the regenerative abilities of spinal-projecting neurons might reflect the summed influences of the chemorepulsive guidance receptors that they express.

The Effects of Excitatory and Inhibitory Social Cues on Cocaine-Seeking Behavior.

Social partners influence the likelihood of using drugs, developing a substance use disorder and relapse to drug use after a period of abstinence. Preclinical studies report that social cues influence the acquisition of cocaine use, the escalation of cocaine use over time, and the compulsive patterns of cocaine use that emerge during an extended binge. The purpose of this study was to examine the effects of social cues on the reinstatement of cocaine-seeking behavior after a period of abstinence. Male rats were obtained at weaning, assigned to triads (three rats/cage), reared to adulthood and implanted with intravenous catheters. Rats from each triad were then assigned to one of three conditions: (1) test rats were trained to self-administer cocaine and were tested for reinstatement; (2) cocaine partners were trained to self-administer cocaine and were predictive of response-contingent cocaine delivery; and (3) abstinent partners were not given access to cocaine and were predictive of extinction. The test rats alternated social partners every 5 days for 20 days such that responding was reinforced with cocaine in the presence of the cocaine partner (S+) for 10 days and not reinforced with cocaine in the presence of the abstinent partner (S−) for 10 days. Responding of the test rats was then extinguished over 7 days under isolated conditions. Tests of reinstatement were then conducted in the presence of the cocaine partner and abstinent partner under extinction conditions. Neither social partner reinstated responding relative to that observed on the final day of extinction; however, responding was greater in the presence of the cocaine partner (S+) than the abstinent partner (S−) during the reinstatement test. These data fail to demonstrate that a social partner reinstates cocaine-seeking behavior after a period of abstinence, but they do indicate that social partners can serve as either excitatory or inhibitory discriminative stimuli to influence drug-seeking responses.

Assays to Examine Transmembrane Semaphorin Function In Vitro.

The semaphorins are a large family of secreted and membrane associated proteins that play numerous key roles in the development and function of the nervous system and other tissues. They have been primarily associated with their function as guidance cues in the developing nervous system. In general, semaphorins have been shown to function as inhibitory guidance cues; however there are also numerous examples where they can function as attractive or permissive cues. Thus it is important to employ a variety of assays to test for semaphorin function. While numerous assays have been established for secreted semaphorins, testing the function of transmembrane semaphorins has been challenging. In this chapter we outline two assays that we have used extensively to test their function. In one assay we examine the effect of a constant source of a transmembrane semaphorin on neurite outgrowth and in a second assay we examine whether neurons will actively avoid growing across islands of cells expressing a transmembrane semaphorin. We have found both assays to be relatively easy to perform and useful to test semaphorin function and signaling.

Food as a supplementary cue triggers seasonal changes in aggression, but not reproduction, in Siberian hamsters

Animals living in temperate regions prepare for harsh winter conditions by responding to environmental cues that signal resource availability (e.g., food, day length). Siberian hamsters (Phodopus sungorus) breed in long, summer-like days (LD, >14h light), i.e., photoperiods, and undergo robust gonadal regression and become more aggressive when exposed to short, winter-like photoperiods that signal impending limited resources (SD, <10h light). When hamsters are reared within an intermediate photoperiod (ID, 13.5h light), they are reproductively active, but undergo gonadal regression in response to mild food restriction (FR) over 6–12weeks. We hypothesized that short-term (1–2weeks) FR in an ID photoperiod would provide a signal of impending limited resources and initiate the seasonal increase in aggression typical of SD photoperiods, as well as alter reproductive behaviors in advance of gonadal regression. To test this, we housed male and female hamsters in LD or ID photoperiods, with ad libitum (AL) access to food or a 90%-AL ration. We tested aggressive behavior after one week and reproductive behavior after two weeks, and subsequently monitored females for pregnancy and litter production. Both sexes displayed increased aggression in the ID-FR treatment. Untreated male intruders were less likely to ejaculate when paired with ID females during reproductive encounters. ID-FR males were undergoing gonadal regression after two weeks, but were more likely to have ejaculated. Female pregnancy and litter characteristics were unaltered by treatment: females were equally likely to achieve pregnancy and produce comparable litters across treatment groups. Collectively, we demonstrate that a signal of diminishing resources in an ID photoperiod is sufficient to trigger seasonal aggression, but that hamsters are reproductively resilient to inhibitory environmental cues in the short term. Broadly, our findings provide an important context for exploring seasonal changes in behavior and physiology from an ultimate perspective.

Age related changes in axon guidance cues in the optic chiasm

PurposeAdult mammalian retinal ganglion cells (RGC) usually fail to regenerate axons post injury. Axon regeneration can be facilitated by several approaches but misguidance of regenerating axons at the optic chiasm is often observed and has been attributed to intrinsic proprieties of RGCs and/or a lack of extrinsic guidance cues in the adult visual system. This study characterizes the guidance cues present in the adult optic chiasm compared to the embryonic visual system.MethodsKnown guidance cues were examined in embryonic and adult optic chiasms of C57 mice by IHC. Radial glial markers (RC2/BLBP/Slit1) and developmental markers (Shh/Pax2) were assessed. RC2, BLBP, Slit1 and Shh are known as inhibitory guidance cues while Pax2 is a permissive guidance cue.ResultsStaining for glial markers RC2 &amp; BLBP was detected immediately superior to the optic chiasm in coronal E15.5 samples. In coronal adult brain samples, RC2 &amp; BLBP staining was observed in the optic chiasm midline; a very different distribution to E15.5 samples. No staining was observed in E15.5 or adult horizontal samples. Slit1 showed expression in the optic chiasm midline and optic tract at E15.5, but no staining was detected in the adult. Shh showed the same pattern as Slit 1 in the optic nerve at E15.5. Pax2 was present in optic nerves of both embryonic and adult samples.ConclusionsHere the profile of guidance cues in the embryonic and adult visual system was characterized. In the developing embryo all markers, known to be crucial for establishing axonal pathways along the optic stalk and optic tract, were present. In the adult visual system Slit1 and Shh were absent, RC2 and BLBP were ectopically expressed, and Pax2 expression was low. These results may explain misguidance of regenerating RGC axons in the adult optic chiasm, highlighting the importance of understanding this environment.

The Neurite Outgrowth Inhibitory Nogo-A-Δ20 Region Is an Intrinsically Disordered Segment Harbouring Three Stretches with Helical Propensity.

Functional recovery from central neurotrauma, such as spinal cord injury, is limited by myelin-associated inhibitory proteins. The most prominent example, Nogo-A, imposes an inhibitory cue for nerve fibre growth via two independent domains: Nogo-A-Δ20 (residues 544–725 of the rat Nogo-A sequence) and Nogo-66 (residues 1026–1091). Inhibitory signalling from these domains causes a collapse of the neuronal growth cone via individual receptor complexes, centred around sphingosine 1-phosphate receptor 2 (S1PR2) for Nogo-A-Δ20 and Nogo receptor 1 (NgR1) for Nogo-66. Whereas the helical conformation of Nogo-66 has been studied extensively, only little structural information is available for the Nogo-A-Δ20 region. We used nuclear magnetic resonance (NMR) spectroscopy to assess potential residual structural propensities of the intrinsically disordered Nogo-A-Δ20. Using triple resonance experiments, we were able to assign 94% of the non-proline backbone residues. While secondary structure analysis and relaxation measurements highlighted the intrinsically disordered character of Nogo-A-Δ20, three stretches comprising residues 561EAIQESL567, 639EAMNVALKALGT650, and 693SNYSEIAK700 form transient α-helical structures. Interestingly, 561EAIQESL567 is situated directly adjacent to one of the most conserved regions of Nogo-A-Δ20 that contains a binding motif for β1-integrin. Likewise, 639EAMNVALKALGT650 partially overlaps with the epitope recognized by 11C7, a Nogo-A-neutralizing antibody that promotes functional recovery from spinal cord injury. Diffusion measurements by pulse-field gradient NMR spectroscopy suggest concentration- and oxidation state-dependent dimerisation of Nogo-A-Δ20. Surprisingly, NMR and isothermal titration calorimetry (ITC) data could not validate previously shown binding of extracellular loops of S1PR2 to Nogo-A-Δ20.

Somatodendritic Expression of JAM2 Inhibits Oligodendrocyte Myelination

Myelination occurs selectively around neuronal axons to increase the efficiency and velocity of action potentials. While oligodendrocytes are capable of myelinating permissive structures in the absence of molecular cues, structurally permissive neuronal somata and dendrites remain unmyelinated. Utilizing a purified spinal cord neuron-oligodendrocyte myelinating co-culture system, we demonstrate that disruption of dynamic neuron-oligodendrocyte signaling by chemical cross-linking results in aberrant myelination of the somatodendritic compartment of neurons. We hypothesize that an inhibitory somatodendritic cue is necessary to prevent non-axonal myelination. Using next-generation sequencing and candidate profiling, we identify neuronal junction adhesion molecule 2 (JAM2) as an inhibitory myelin-guidance molecule. Taken together, our results demonstrate that the somatodendritic compartment directly inhibits myelination and suggest a model in which broadly indiscriminate myelination is tailored by inhibitory signaling to meet local myelination requirements.

Dissociable Fronto-Operculum-Insula Control Signals for Anticipation and Detection of Inhibitory Sensory Cue.

The ability to anticipate and detect behaviorally salient stimuli is important for virtually all adaptive behaviors, including inhibitory control that requires the withholding of prepotent responses when instructed by external cues. Although right fronto-operculum-insula (FOI), encompassing the anterior insular cortex (rAI) and inferior frontal cortex (rIFC), involvement in inhibitory control is well established, little is known about signaling mechanisms underlying their differential roles in detection and anticipation of salient inhibitory cues. Here we use 2 independent functional magnetic resonance imaging data sets to investigate dynamic causal interactions of the rAI and rIFC, with sensory cortex during detection and anticipation of inhibitory cues. Across 2 different experiments involving auditory and visual inhibitory cues, we demonstrate that primary sensory cortex has a stronger causal influence on rAI than on rIFC, suggesting a greater role for the rAI in detection of salient inhibitory cues. Crucially, a Bayesian prediction model of subjective trial-by-trial changes in inhibitory cue anticipation revealed that the strength of causal influences from rIFC to rAI increased significantly on trials in which participants had higher anticipation of inhibitory cues. Together, these results demonstrate the dissociable bottom-up and top-down roles of distinctFOI regions in detection and anticipation of behaviorally salient cues across multiple sensory modalities.

How inhibitory cues can both constrain and promote cell migration.

Collective cell migration is a common feature in both embryogenesis and metastasis. By coupling studies of neural crest migration in vivo and in vitro with mathematical modeling, Szabó et al. (2016, J. Cell Biol., http://dx.doi.org/10.1083/jcb.201602083) demonstrate that the proteoglycan versican forms a physical boundary that constrains neural crest cells to discrete streams, in turn facilitating their migration.

Too (mentally) busy to chill: Cognitive load and inhibitory cues interact to moderate triggered displaced aggression.

Inhibitory information can be expected to reduce triggered displaced aggression by signaling the potential for negative consequences as a result of acting aggressively. We examined how cognitive load might interfere with these aggression-reducing effects of inhibitory cues. Participants (N = 80) were randomly assigned to a condition in a 2 (cognitive load: high/low) × 2 (inhibiting cues: yes/no) between-subjects design. Following procedures in the TDA paradigm, participants received an initial provocation from the experimenter and a subsequent triggering annoyance from another individual. In the inhibitory cue condition, participants were told, before they had the opportunity to aggress, that others would learn of their aggressive responses. In the high cognitive load condition, participants rehearsed a 10-digit number while aggressing. Those in the low cognitive load condition rehearsed a three digit number. We found significant main effects of cognitive load and inhibitory cue, which were qualified by the expected load × inhibitory cue interaction. Thus, inhibitory cues reduced displaced aggression under low-cognitive load. However, when participants in the inhibitory cue condition were under cognitive load, aggression increased, suggesting that mental busyness interfered with the full use of inhibitory information. Aggr. Behav. 42:598-604, 2016. © 2016 Wiley Periodicals, Inc.