Inhibitory Stimuli Research Articles

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.

The Use of Differential Reinforcement of Other Behaviours to Establish Inhibitory Stimulus Control for the Management of Vocal Stereotypy in Children with Autism

ABSTRACTObjective: This study examined the efficacy of an inhibitory stimulus control procedure (ISCP) for the management of vocal stereotypy in three children with autism. Method: During discrimination training, implemented within a changing criterion design, participants were taught that there were no consequences for vocal stereotypy in the absence of an inhibitory stimulus but that differential reinforcement procedures were in effect in the presence of the stimulus. Functional control of the inhibitory stimulus was subsequently assessed within a reversal design. Results: Inhibitory stimulus control was established during discrimination training, with participants inhibiting vocal stereotypy for 30 min periods in the presence of the inhibitory stimulus. Reductions in vocal stereotypy were maintained in the presence of the inhibitory stimulus and in the absence of further programmed consequences. Discussion: This study extends current knowledge by demonstrating the efficacy of ISCPs paired with reinforcement only, and illustrating the functional control of the inhibitory stimulus.

Dynamics of transitions from anti-phase to multiple in-phase synchronizations in inhibitory coupled bursting neurons

Transition from anti-phase to in-phase synchronizations in inhibitory coupled bursting neurons is very important for locomotor rhythms of animals. Here, multiple in-phase (complete), anti-phase, and phase synchronous bursting patterns are simulated in inhibitory coupled map-based model neurons with bursting patterns, and synchronization transitions between these patterns are simulated in a two-dimensional parameter space of the coupling strength and time delay. Time delay-induced transition from anti-phase to in-phase synchronous bursting behaviors matches those observed in a biological experiment on the inhibitory coupled neurons in the stomatogastric ganglion of lobster. Furthermore, bursting patterns of the in-phase (complete) synchronous behaviors can be well interpreted with the dynamic responses of an isolated single neuron to a negative square current whose action time, duration, and strength are similar to those of the inhibitory coupling current modulated by the coupling strength and time delay. The burst of the synchronous behaviors manifests the same pattern as the square negative current-induced burst of the isolated single neuron, which is acquired with the fast–slow variable dissection method. The results not only present novel nonlinear phenomenon of the time delay-induced multiple synchronous behaviors and synchronization transitions, but also provide a reasonable interpretation with the different dynamic responses of map-based bursting model neuron to an external inhibitory stimulus applied at different phases.

Complex Interactions of excitatory and inhibitory stimuli in the vascular endothelium

The endothelium is the single, innermost, layer of cells in blood vessels and it controls almost all cardiovascular functions. The endothelium regulates immune responses, blood coagulation, angiogenesis, vessel repair, and vascular permeability. To regulate function, the endothelium continuously monitors multiple chemicals that are circulating in the blood or derived from nearby cells (e.g. endocrine, paracrine, autocrine or neurotransmitter signals). These chemicals each provide cues to physiological status. The chemicals are detected and processed selectively by the endothelium to direct resources that adjust physiological function. Some chemicals provide conflicting signals to the endothelium such as those which promote or inhibit vascular tone. How conflicting signals are detected and managed by the endothelium is not understood. The present study was undertaken to determine how the endothelium selectively processes conflicting information. To monitor the behaviour of the endothelium, changes in endothelial cytosolic Ca2+ concentration were measured in ~200 endothelial cells in small mesenteric arteries using the indicator Cal‐520 and high‐resolution imaging. Changes in cytosolic Ca2+ concentration underlies virtually all endothelial functions and so provides a useful measure of endothelial activity. The vasodilator substance acetylcholine evoked Ca2+ increases that initiated in small clusters of cells. As the concentration of acetylcholine increased, the amplitude of the Ca2+ rise and the number of activated cells increased. To examine the interaction of excitatory and inhibitory inputs, acetylcholine (as an excitatory input) at an EC75 (15nM) was used. In the first series of experiments the vasoconstrictor alpha‐adreneric agonist phenylephrine was used. Phenylephrine (10 μM) did not itself evoke any detectable Ca2+ signals in the endothelium. However, phenylephrine inhibited the Ca2+ rise evoked by acetylcholine (15 nM). Phenylephrine inhibited the amplitude of the response in each activated cell and the number of cells activated. By inhibiting endothelial activity, phenylephrine will increase the contractile response operating on the smooth muscle cells. The vasoconstrictor agonist angiotensin (10 μM) did not evoke Ca2+ increases when applied by itself. However, angiotensin increased the amplitude of the Ca2+ response to acetylcholine in each activated cell. The number of cells activated did not change. This effect of angiotensin on the endothelium may serve to limit a vasoconstrictor response. Together these data reveal complex interaction occur between excitatory and inhibitory stimuli acting on the endothelium.Support or Funding InformationSupported by the Wellcome Trust and British Heart FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Characteristics of Saccadic Responses in an Experimental “Go/No Go” Scheme in Healthy Subjects and Those at Ultra High Risk of Developing Schizophrenia

Studies using presentation of visual stimuli in a “go/no go” scheme revealed differences in saccadic responses in healthy subjects and patients at ultra high risk of developing schizophrenia. Patients showed a greater number of erroneous responses to inhibitory stimuli and shorter latent periods (LP) for correct and erroneous saccades. Opposite asymmetries were demonstrated for the LP of saccadic responses in healthy subjects and patients: the LP of saccades to the right was shorter than to the left in healthy subjects, while the LP of saccades to the right was longer than to the left in patients. These data showed that impairments to the mechanisms controlling voluntary behavior occur at the pre-manifest stage of the course of schizophrenia when there is a ultra high risk of developing this condition. The results obtained here suggest that patients at ultra high risk of developing schizophrenia have impairments to the processes of voluntary and involuntary attention, as well as to the processes of inhibitory control, which may be due to dysfunction of the right prefrontal cortex and weakening of top down influences in the attention and inhibitory control systems.

Synaptic E-I Balance Underlies Efficient Neural Coding.

Both theoretical and experimental evidence indicate that synaptic excitation and inhibition in the cerebral cortex are well-balanced during the resting state and sensory processing. Here, we briefly summarize the evidence for how neural circuits are adjusted to achieve this balance. Then, we discuss how such excitatory and inhibitory balance shapes stimulus representation and information propagation, two basic functions of neural coding. We also point out the benefit of adopting such a balance during neural coding. We conclude that excitatory and inhibitory balance may be a fundamental mechanism underlying efficient coding.

Negative Feedback Mediated by Fast Inhibitory Autapse Enhances Neuronal Oscillations Near a Hopf Bifurcation Point

One-parameter and two-parameter bifurcations of the Morris–Lecar (ML) neuron model with and without the fast inhibitory autapse, which is a synapse from a neuron onto itself, are investigated. The ML neuron model without autapse manifests an inverse Hopf bifurcation point from firing to a depolarized resting state with high level of membrane potential, with increasing depolarization current. When a fast inhibitory autapse is introduced, a negative feedback or inhibitory current is applied to the ML model. With increasing conductance of the autapse to middle level, the depolarized resting state near the inverse Hopf bifurcation point can change to oscillation and the parameter region of the oscillation becomes wide, which can be well interpreted by the dynamic responses of the depolarized resting state to the inhibitory current stimulus mediated by the autapse. The enlargement of the parameter region of the oscillation induced by the negative feedback presents a novel viewpoint different from the traditional one that inhibitory synapse often suppresses the neuronal oscillation activities. Furthermore, complex nonlinear dynamics such as the coexisting behaviors and codimension-2 bifurcations including the Bautin and cusp bifurcations are acquired. The relationship between the bifurcations and the depolarization block, a physiological concept that indicates a neuron can enter resting state when receiving the depolarization current, is discussed.

Examining the influence of CS duration and US density on cue-potentiated feeding through analyses of licking microstructure

In the current study, groups of mice were trained with either short (20s) or long (120s) conditioned stimulus (CS) durations associated with different rates of sucrose unconditioned stimulus (US) delivery, to examine whether different behavioral forms of cue-potentiated feeding in sated mice would be evoked. In training mice received presentations of an auditory CS for 20s during which a sucrose US was delivered at a density of 1/9s (Group-20-s). A second group of mice received an auditory CS for 120s and a US density of 1/49s (Group-120-s). During training, a shorter CS duration and higher rate of US delivery resulted in greater acquisition of food cup responding, and during the test stage Group-20-s mice also displayed higher CS evoked lick rates, though all mice showed cue-potentiated feeding. An analysis of licking microstructure revealed that Group-120-s mice displayed CS evoked licking behavior that reflected an increase in the perceived palatability of the sucrose US. These findings are discussed with respect to the influence of CS duration and US density on associatively activated sensory and affective representations of a US, and contrast mediated effects resulting from presentation of excitatory and inhibitory conditioned stimuli.

P 65 Navigated repetitive transcranial magnetic stimulation – therapeutic use in early rehabilitation treatment after stroke

MRI navigated repetitive transcranial magnetic stimulation (nTMS) provides a new tool for neuromodulation – we report on its effects on recovery of brain function in a setting of inpatient rehabilitation early after stroke. MRI based nTMS (inhibitory stimulus paradigm, 900 pulses at an intensity of 110% motor threshold, applied at 1 Hz) oft the contralesional primary motor cortex. Each patient participated in a median of 7 stimulation sessions, 3 sessions per week. Each stimulation session was followed by an immediate session of physical therapy, logopedic or ergotherapeutic treatment. A total of 27 cases were subject to at least 3 nTMS sessions (range 3–19 sessions) in addition to the standard multimodal therapeutic setting. The vast majority of cases experienced an improvement of motor deficit, neglect and dysphagia. The activities of daily life (Barthel) index increased from 15 to 30 points median. Two thirds of the patients were enabled to continue rehabilitation in phase C. Adverse events did not occur. The application of nTMS for early rehabilitation purposes in stroke patients is safe and effective. It appears to uncover a regeneration potential still hidden. Thus it may become a useful therapeutic adjunct to the standard multimodal approach.

Effect of Different Osmolalities, CHO Types, and [CHO] on Gastric Emptying in Humans

This study investigated the effect of beverage osmolalities, carbohydrate (CHO) type, and CHO concentration on gastric emptying in euhydrated subjects at rest. The gastric emptying of water (W), four glucose beverages (2%, 4%, 6%, and 8% glucose: 2G, 4G, 6G, and 8G), and four sucrose beverages (2%, 4%, 6%, and 8% sucrose: 2S, 4S, 6S, and 8S) were determined in eight healthy subjects using the modified George double-sampling technique. Subjects ingested a beverage (7 mL·kg body weight) containing 25 ppm phenol red as quickly as possible (≤1.0 min), and subsequent gastric and blood samples were collected every 10 min for 40 min. A linear regression and a repeated-measures ANOVA were used for statistical analysis. The gastric secretion volume was not significantly different among beverages across time. Gastric residual beverage volume (GRBV) at each sampling time point was not different among 2S, 4S, 6S, 8S, and water (P > 0.05). The 8G resulted in a significantly greater GRBV compared with other beverages at 20, 30, and 40 min (P < 0.05). GRBV from 6G was significantly higher than 2G at 30 min, but no other statistical differences were found among W, 2G, 4G, and 6G. The 8S had a greater GRBV compared with W at 40 min (P < 0.05). Mean gastric osmolality positively correlated to mean GRBV (r = 0.93). Gastric emptying rate was negatively correlated to the calories emptied (r = 0.84) with a greater effect from glucose beverages compared with sucrose beverages. These data suggest that glucose exerts a stronger inhibitory stimulus compared with sucrose on gastric emptying and that a physiological threshold exists for the combined influence of glucose concentration and beverage osmolality to trigger the feedback inhibition of gastric emptying.

The role of safety signals in fear extinction: An analogue study

Background and objectivesSafety signals are conditioned inhibitory stimuli that indicate the absence of unconditioned stimuli. It is not clear whether the presence of safety signals is detrimental or beneficial in extinction-based interventions. The purpose of this study was to evaluate the effect of safety signals on autonomic and expectancy fear-related responses. MethodsFollowing the conditional discrimination paradigm (AX +, BX-), undergraduate students (N = 48) underwent an aversive conditioning procedure, while safety signals were experimentally created. Participants were randomly assigned to one of two conditions during extinction: presence or absence of safety signals. ResultsSignificant reductions of fear-related responses were found in both groups. Expectancy measures showed that the presence of safety signals did not interfere with reduction of fear related responses at follow-up. LimitationsThe analogue nature of the study affects its ecological validity. There are some methodological issues. ConclusionsSafety signals did not interfere with extinction learning. Attention may be a mechanism associated with the maintenance of fear responses.

Enhanced Sensitivity to Hyperpolarizing Inhibition in Mesoaccumbal Relative to Nigrostriatal Dopamine Neuron Subpopulations.

Midbrain dopamine neurons recorded in vivo pause their firing in response to reward omission and aversive stimuli. While the initiation of pauses typically involves synaptic or modulatory input, intrinsic membrane properties may also enhance or limit hyperpolarization, raising the question of how intrinsic conductances shape pauses in dopamine neurons. Using retrograde labeling and electrophysiological techniques combined with computational modeling, we examined the intrinsic conductances that shape pauses evoked by current injections and synaptic stimulation in subpopulations of dopamine neurons grouped according to their axonal projections to the nucleus accumbens or dorsal striatum in mice. Testing across a range of conditions and pulse durations, we found that mesoaccumbal and nigrostriatal neurons differ substantially in rebound properties with mesoaccumbal neurons displaying significantly longer delays to spiking following hyperpolarization. The underlying mechanism involves an inactivating potassium (IA) current with decay time constants of up to 225 ms, and small-amplitude hyperpolarization-activated currents (IH), characteristics that were most often observed in mesoaccumbal neurons. Pharmacological block of IA completely abolished rebound delays and, importantly, shortened synaptically evoked inhibitory pauses, thereby demonstrating the involvement of A-type potassium channels in prolonging pauses evoked by GABAergic inhibition. Therefore, these results show that mesoaccumbal and nigrostriatal neurons display differential responses to hyperpolarizing inhibitory stimuli that favors a higher sensitivity to inhibition in mesoaccumbal neurons. These findings may explain, in part, observations from in vivo experiments that ventral tegmental area neurons tend to exhibit longer aversive pauses relative to SNc neurons.SIGNIFICANCE STATEMENT Our study examines rebound, postburst, and synaptically evoked inhibitory pauses in subpopulations of midbrain dopamine neurons. We show that pauses in dopamine neuron firing, evoked by either stimulation of GABAergic inputs or hyperpolarizing current injections, are enhanced by a subclass of potassium conductances that are recruited at voltages below spike threshold. Importantly, A-type potassium currents recorded in mesoaccumbal neurons displayed substantially slower inactivation kinetics, which, combined with weaker expression of hyperpolarization-activated currents, lengthened hyperpolarization-induced delays in spiking relative to nigrostriatal neurons. These results suggest that input integration differs among dopamine neurons favoring higher sensitivity to inhibition in mesoaccumbal neurons and may partially explain in vivo observations that ventral tegmental area neurons exhibit longer aversive pauses relative to SNc neurons.

Developing and demonstrating inhibitory stimulus control over repetitive behavior

Developing inhibitory stimulus control over repetitive behavior minimizes the social and learning disruptions caused by this behavior while allowing individuals to continue to access this source of reinforcement at nonproblematic times. These procedures involve allowing repetitive behaviors to occur in some stimulus conditions (S+) and blocking the repetitive behavior in order to disrupt the response–reinforcer relation in other stimulus conditions (S‐) such that the onset of the S‐ period results in rapid and sustained reductions in repetitive behavior. However, the demonstration of stimulus control exerted by the S‐ has often been confounded with participants' exposure to programmed reductive contingencies (i.e., behavior is reduced due to direct contact with contingencies rather than the programmed antecedent stimuli). The current study both developed and demonstrated the suppressive effects of S‐ presentation upon repetitive behavior with two children diagnosed with autism spectrum disorders. These demonstration techniques involved (a) introducing the S‐ into novel environments without the programmed contingencies that we used to establish discriminative control, (b) evaluating the reductive effects of programmed contingencies with and without the associated discriminative stimuli, and (c) evaluating latencies to the onset of repetitive behavior given S+ and S‐ presentations.

Synaptic Protein Dynamics Measured by Fluorescence Correlation Spectroscopy

The activity dependent adjustment of synaptic strength (synaptic plasticity) involves the reorganization of post-synaptic proteins. The fast diffusion of synaptic proteins has been shown to play an important role in such molecular rearrangements, but the dynamic events that lead to the formation of molecular complexes are still poorly understood. Taking advantages of Single Particle Tracking (SPT) and FRAP approaches, our group has recently demonstrated that during inhibitory long term potentiation stimuli (iLTP) Gephyrin and GABAA receptors are accumulated at post-synaptic inhibitory sites. In addition we have shown that the synaptic clustering of the scaffold protein gephyrin do not precede the synaptic inclusion of GABA receptors. However, the coordinated dynamics of gephyrin and GABAA receptors outside and inside the synapse remain to be elucidated. To investigate the diffusion dynamics of the main synaptic proteins we exploited here Fluorescence Correlation Spectroscopy (FCS), an established technique to study the mobility of molecules and to measure the protein diffusion parameters with high statistics in unperturbed live cell, in both the plasma membrane and the cytoplasmic space. We calibrated an FCS method (FCS) to study the coordinated multilevel organization of receptors and adhesion molecules that laterally diffuse on the plasma membrane and the scaffold proteins that diffuse in the cytoplasmic space. Our data suggest that, the scaffold protein freely diffuse in the extrasynaptic space and is suddenly immobilized at both synaptic site and extrasynaptic clusters. This approach may clarify the coordinated diffusion of membrane synaptic proteins and cytoplasmic scaffold proteins thus clarifying the mechanisms of synaptic clustering in basal conditions and during synaptic plasticity.

A systematic review and evaluation of inhibitory stimulus control procedures as a treatment for stereotyped behavior among individuals with autism

ABSTRACTPurpose: Stereotypy is pervasive among persons with autism and may impact negatively on social inclusion and learning. The implementation of resource-intensive behavioral interventions to decrease these behaviors has been questioned. Inhibitory stimulus control procedures (ISCPs) comprise a type of antecedent-based intervention that has been proposed as an effective treatment approach for stereotypy but has received limited research attention to date. Method: The current systematic review sought to examine and synthesize the literature reporting applications of ISCPs in the treatment of stereotypy among persons with autism. Treatment outcomes were analyzed quantitatively and the status of ISCPs as evidence-based practice was evaluated in accordance with the National Autism Center’s National Standards Report guidelines. Results: A total of 11 studies were reviewed with results indicating that ISCPs constituted an emerging treatment for the stereotypy exhibited by persons with autism. Conclusions: ISCPs comprise a promising intervention for stereotyped behavior but further research is required.

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.

Induction of a reproductive-specific cuticular hydrocarbon profile by a juvenile hormone analog in the termite Zootermopsis nevadensis

Establishment and maintenance of the reproductive division of labor within social insect colonies relies on clear communication between nestmates. Fertile members convey their status to prevent others from becoming reproductively active. Recent findings in some basal termites indicate that cuticular hydrocarbon profiles may indicate reproductive state, but there is little evidence to show a direct link between reproductive status and hydrocarbon production—a prerequisite for an “honest” fertility signal. Here, we report that the putative signaling mechanism is influenced by juvenile hormone (JH), a primary regulator of gonadal development and activity in insects. Topical application of a JH-analog (pyriproxyfen) to reproductively inactive alates of the basal dampwood termite Zootermopsis nevadensis induced both females and males to express significantly more of a reproductive-specific hydrocarbon (6,9,17-tritriacontatriene). However, the JH-analog did not significantly enhance gonadal development or activity in treated termites beyond what is usually observed in maturing alates released from the inhibitory stimuli of their natal nest. These results suggest that a rise in JH following disinhibition drives the expression of reproductive-specific hydrocarbons, but that an individual’s hydrocarbon profile is not directly linked to its gonadal state. Rather than directly driving the expression of reproductive-specific hydrocarbons, the gonads may act indirectly through their influence on circulating JH.

Abstract A10: The hypoxic response in natural killer cells: Linking cytoxicity and tumor immune surveillance to angiogenesis

Abstract Hypoxia-inducible transcription factors (HIFs) are central mediators of cellular adaptation to low oxygen and play a pivotal role in inflammatory responses. Natural Killer (NK) cells, unifying characteristics of innate and adaptive immunity, are cytotoxic innate lymphoid cells with a unique ability to instantly recognize and kill “aberrant” cancer cells while sparing “normal” cells. Owing to these tumoricidal features, NK cells are able to restrict primary tumor growth and limit metastatic spread. By genetic targeting HIFs in NK cells HIFs, we define a crucial role of HIF-1 in NK cell function and cancer immune surveillance. We show that NK cells preferentially infiltrate into hypoxic zones of solid primary tumors and that HIF-1-deficiency in NK cells slows impairs primary tumor growth as well as distant metastasis. This is due to reduced susceptibility of HIF-1-deficient NK cells to tumor cell-derived inhibitory stimuli, resulting in improved recognition and killing of tumor cells. Furthermore, we define the hypoxic response in NK cells as a critical mediator of tumor angiogenesis. Paradoxically, HIF-1-deficiency in NK cells results in decreased expression of various angiostatic factors within the tumor microenvironment, resulting in unproductive tumor angiogenesis, characterized by immature, non-functional vessel and severe tumor hypoxia. This suggests that the hypoxic response in NK cells slows down overall tumor angiogenesis in order to allow for vessel formation in a more coordinated fashion. In summary, we define HIF-1 as a critical mediator of NK cell effector function and cancer immune surveillance. Secondly, we show that HIF-1 in NK cells acts as a negative regulator of tumor angiogenesis that ensures the fine-tuning of the angiogenic response. These results indicate that exploiting the hypoxic response in NK cells may represent a novel therapeutic avenue. Citation Format: Ewelina Krzywinska, Chahrazade Kantari-Mimoun, Magali Castells, Dagmar Gotthardt, Yann Kerdiles, Ralph Klose, Joachim Fandrey, Veronika Sexl, Christian Stockmann. The hypoxic response in natural killer cells: Linking cytoxicity and tumor immune surveillance to angiogenesis. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A10.

Extinction of inhibition after serial and simultaneous feature negative discrimination training.

Two experiments using a conditioned suppression procedure with rats found that following training, nonreinforced presentations of an inhibitory feature stimulus (X) had different effects, depending on whether a serial (A+, XA−) or a simultaneous (A+, A→X−) feature negative discrimination procedure was used to establish the inhibition. Those presentations exhanced X's inhibitory power after simultaneous feature negative training, but reduced X's inhibitory power after serial feature negative training. These data suggest that the nature of inhibition established in feature negative discriminations depends on the temporal arrangement of stimuli.

A cognitive hypothesis of the development of differentiative cortical inhibition in humans

Positive and inhibitory conditioning stimuli (Go/NoGo) were presented to healthy adults (n = 35) in an experimental setting for angry face recognition with short intervals between the setting (face), conditioning, and triggering stimuli. A modification of the previously used experimental conditions that consisted in a reduction of the duration of the interstimulus intervals promoted an increase in attitude flexibility (expansion of the group of subjects that made no identification errors at the stage of set testing). The improvement of cognitive performance was accompanied by expansion of the zone of α-oscillation synchronization induced by the NoGo inhibitory conditioning stimulus. Synchronization of α-oscillations was less pronounced in subjects with a rigid cognitive set. Thus, the cognitive hypothesis of cortical inhibition (termed “internal inhibition” by I.P. Pavlov) has been confirmed. The concept of the emergence of top-down inhibitory effects in the prefrontal cortex, implicit internal representation, and selective modulation of attention is discussed.