Cognitive Control Processes and Defense Mechanisms That Influence Aggressive Reactions: Toward an Integration of Socio-Cognitive and Psychodynamic Models of Aggression

Research on cognitive processes has primarily focused on cognitive control and inhibitory processes to the detriment of other psychological processes, such as defense mechanisms (DMs), which can be used to modify aggressive impulses as well as self/other images during interpersonal conflicts. First, we conducted an in-depth theoretical analysis of three socio-cognitive models and three psychodynamic models and compared main propositions regarding the source of aggression and processes that influence its enactment. Second, 32 participants completed the Hostile Expectancy Violation Paradigm (HEVP) in which scenarios describe a hostile vs. non-hostile social context followed by a character's ambiguous aversive behavior. The N400 effect to critical words that violate expected hostile vs. non-hostile intent of the behavior was analyzed. Prepotent response inhibition was measured using a Stop Signal task (SST) and DMs were assessed with the Defense Style Questionnaire (DSQ-60). Results showed that reactive aggression and HIA were not significantly correlated with response inhibition but were significantly positively and negatively correlated with image distorting defense style and adaptive defense style, respectively. The present article has highlighted the importance of integrating socio-cognitive and psychodynamic models to account for the full complexity underlying psychological processes that influence reactive aggressive behavior.

Changes in gaseous concentration of alkylpyrazine analogs affect mouse avoidance behavior

The Y-maze is often used to detect subtle differences between similar odor sources; however, very little information is available about the dispersion of odor plumes in the Y-maze. Using headspace solid-phase microextraction (HS-SPME) in conjunction with a GC-MS system, we quantified alkylpyrazine analogs in the Y-maze. Rapid extraction of volatile compounds in the vapor phase enabled accurate quantitative analysis of temporal changes in the levels of gaseous alkylpyrazine analogs at several locations in the Y-maze. We conducted behavioral tests of mice in response to these volatiles and identified a positive relationship between the rate of increase in gaseous concentration and the induced avoidance rate. Our results demonstrate that the Y-maze is a simple but reliable apparatus for behavioral studies of olfaction. Our findings show that the HS-SPME fast extraction method could quantify how gaseous concentrations of alkylpyrazine analogs change over time, and that temporal increases in alkylpyrazine concentration were correlated with induction of aversive behavior in mice.

Dysfunction of Glutamate Delta-1 Receptor-Cerebellin 1 Trans-Synaptic Signaling in the Central Amygdala in Chronic Pain

Chronic pain is a debilitating condition involving neuronal dysfunction, but the synaptic mechanisms underlying the persistence of pain are still poorly understood. We found that the synaptic organizer glutamate delta 1 receptor (GluD1) is expressed postsynaptically at parabrachio-central laterocapsular amygdala (PB-CeLC) glutamatergic synapses at axo-somatic and punctate locations on protein kinase C δ -positive (PKCδ+) neurons. Deletion of GluD1 impairs excitatory neurotransmission at the PB-CeLC synapses. In inflammatory and neuropathic pain models, GluD1 and its partner cerebellin 1 (Cbln1) are downregulated while AMPA receptor is upregulated. A single infusion of recombinant Cbln1 into the central amygdala led to sustained mitigation of behavioral pain parameters and normalized hyperexcitability of central amygdala neurons. Cbln2 was ineffective under these conditions and the effect of Cbln1 was antagonized by GluD1 ligand D-serine. The behavioral effect of Cbln1 was GluD1-dependent and showed lateralization to the right central amygdala. Selective ablation of GluD1 from the central amygdala or injection of Cbln1 into the central amygdala in normal animals led to changes in averse and fear-learning behaviors. Thus, GluD1-Cbln1 signaling in the central amygdala is a teaching signal for aversive behavior but its sustained dysregulation underlies persistence of pain. Significance statement: Chronic pain is a debilitating condition which involves synaptic dysfunction, but the underlying mechanisms are not fully understood. Our studies identify a novel mechanism involving structural synaptic changes in the amygdala caused by impaired GluD1-Cbln1 signaling in inflammatory and neuropathic pain behaviors. We also identify a novel means to mitigate pain in these conditions using protein therapeutics.

Improved Oral Health and Adaptation to Treatment in Dogs Using Manual or Ultrasonic Toothbrush or Textile of Nylon or Microfiber for Active Dental Home Care

Poor oral health is a common problem in dogs causing pain and impaired welfare. The gold standard to maintain good oral health and prevent periodontitis is daily tooth brushing. However, many dog owners find it difficult, and dogs often show aversive behavior. There are several different tools available, and in this intra-subject study, four different active dental home care treatment options were examined: manual and ultrasonic toothbrush, a nylon glove, and a microfiber finger cloth. The treatments were evaluated for efficacy against gingivitis, plaque, and calculus in beagle dogs. Each dog received two treatments on the buccal sides of the teeth once daily, either two types of toothbrushes (N = 10) or two types of textiles (N = 11), on separate sides of the mouth. The dogs’ teeth were assessed before and after the five-week treatment period, with the assessor blinded by additional, similar dogs (N = 7). The study also assessed the dogs’ stress levels during treatment using a fear, anxiety, stress (FAS) protocol. All four treatments improved dog oral health, reducing gingivitis and plaque. Furthermore, the amount of calculus also decreased in some individuals. Adaptation to dental care occurred in the dogs over time. This information can be used to encourage dog owners to brush their dogs’ teeth.

CONDITIONED REFLEX MECHANISMS OF ADAPTATION TO ADDITIONAL BREATHING RESISTANCE

The problem of adaptation to additional breathing resistance has recently become more urgent due to the growth of bronchopulmonary diseases. Therefore, there is a natural interest in non-drug strategies compensating resistive breathing in humans. The aim of the study was to assess conditioned reflex changes in the functional state of the subjects under additional breathing resistance. Materials and Methods. The work was carried out on 55 practically healthy subjects of both sexes, aged 18–36. Additional breathing resistance was modeled by inspiratory resistive loads of 40, 60, 70, and 80 % of the maximum intraoral pressure. The conditioned respiratory reflex to resistive respiratory load was developed as a short-delayed conditioned signal with a 30-second period of isolated action. The authors examined behavioral, vegetative, gas and energy indicators of the organism before and after the formation of a conditioned reflex. Results. It was observed that conditioned reflex shifts of physiological parameters in the process of adaptation to additional breathing resistance differ significantly from the corresponding unconditioned reflex changes both in nature and in intensity. Conditioned reflex mechanisms reduce the intensity of shifts in the motor component of the external respiration system, which, apparently, is the main reason to decrease the aversive behavior. Conclusion. Behavioral changes after the formation of a conditioned respiratory reflex to additional respiratory resistance are characterized by a decrease in aversive behavior patterns. The conditioned reflex realization of increasing resistive loads is expressed in a lower physiological cost of adaptation to additional respiratory resistance relative to the unconditioned reflex type of realization. Keywords: adaptation, conditioned respiratory reflex, additional breathing resistance. Проблема приспособления к дополнительному респираторному сопротивлению в последнее время становится все более актуальной в связи с ростом бронхолегочных заболеваний. Поэтому естественен интерес к нелекарственным механизмам компенсации резистивного дыхания человека. Целью исследования являлась оценка условно-рефлекторных изменений функционального состояния испытуемых в условиях дополнительного респираторного сопротивления. Материалы и методы. Работа проведена на 55 практически здоровых испытуемых обоего пола в возрасте от 18 до 36 лет. Дополнительное респираторное сопротивление моделировалось инспираторными резистивными нагрузками величиной 40, 60, 70 и 80 % от максимального внутриротового давления. Условный дыхательный рефлекс на резистивные дыхательные нагрузки вырабатывался по типу короткоотставленного с периодом изолированного действия условного сигнала 30 с. Исследовались поведенческие, вегетативные, газовые и энергетические показатели организма до и после формирования условного рефлекса. Результаты. Показано, что условно-рефлекторные сдвиги физиологических показателей в процессе приспособления к дополнительному респираторному сопротивлению существенно отличаются от соответствующих безусловно-рефлекторных изменений как по характеру, так и по интенсивности. Условно-рефлекторные механизмы уменьшают интенсивность сдвигов моторного компонента системы внешнего дыхания, что, по-видимому, является основной причиной снижения вероятности появления аверсивного поведения. Выводы. Поведенческие изменения после формирования условного дыхательного рефлекса на дополнительное респираторное сопротивление характеризуются снижением вероятности появления аверсивных форм поведения. Условно-рефлекторная реализация возрастающих по интенсивности резистивных нагрузок выражается в меньшей физиологической стоимости приспособления к дополнительному респираторному сопротивлению относительно безусловно-рефлекторного типа реализации. Ключевые слова: приспособление, условный дыхательный рефлекс, дополнительное респираторное сопротивление.

CGRP induces migraine-like symptoms in mice during both the active and inactive phases

Background Circadian patterns of migraine attacks have been reported by patients but remain understudied. In animal models, circadian phases are generally not taken into consideration. In particular, rodents are nocturnal animals, yet they are most often tested during their inactive phase during the day. This study aims to test the validity of CGRP-induced behavioral changes in mice by comparing responses during the active and inactive phases. Methods Male and female mice of the outbred CD1 strain were administered vehicle (PBS) or CGRP (0.1 mg/kg, i.p.) to induce migraine-like symptoms. Animals were tested for activity (homecage movement and voluntary wheel running), light aversive behavior, and spontaneous pain at different times of the day and night. Results Peripheral administration of CGRP decreased the activity of mice during the first hour after administration, induced light aversive behavior, and spontaneous pain during that same period of time. Both phenotypes were observed no matter what time of the day or night they were assessed. Conclusions A decrease in wheel activity is an additional clinically relevant phenotype observed in this model, which is reminiscent of the reduction in normal physical activity observed in migraine patients. The ability of peripheral CGRP to induce migraine-like symptoms in mice is independent of the phase of the circadian cycle. Therefore, preclinical assessment of migraine-like phenotypes can likely be done during the more convenient inactive phase of mice.

Microbial colonization induces histone acetylation critical for inherited gut-germline-neural signaling

The gut-neural axis plays a critical role in the control of several physiological processes, including the communication of signals from the microbiome to the nervous system, which affects learning, memory, and behavior. However, the pathways involved in gut-neural signaling of gut-governed behaviors remain unclear. We found that the intestinal distension caused by the bacterium Pseudomonas aeruginosa induces histone H4 Lys8 acetylation (H4K8ac) in the germline of Caenorhabditis elegans, which is required for both a bacterial aversion behavior and its transmission to the next generation. We show that induction of H4K8ac in the germline is essential for bacterial aversion and that a 14-3-3 chaperone protein family member, PAR-5, is required for H4K8ac. Our findings highlight a role for H4K8ac in the germline not only in the intergenerational transmission of pathogen avoidance but also in the transmission of pathogenic cues that travel through the gut-neural axis to control the aversive behavior.

Roles for the Dorsal Striatum in Aversive Behavior

The ability to identify and avoid environmental stimuli that signal danger is essential to survival. Our understanding of how the brain encodes aversive behaviors has been primarily focused on roles for the amygdala, hippocampus (HIPP), prefrontal cortex, ventral midbrain, and ventral striatum. Relatively little attention has been paid to contributions from the dorsal striatum (DS) to aversive learning, despite its well-established role in stimulus-response learning. Here, we review studies exploring the role of DS in aversive learning, including different roles for the dorsomedial and dorsolateral striatum in Pavlovian fear conditioning as well as innate and inhibitory avoidance (IA) behaviors. We outline how future investigation might determine specific contributions from DS subregions, cell types, and connections that contribute to aversive behavior.

Toxic stress-specific cytoprotective responses regulate learned behavioral decisions in C. elegans

Background Recognition of stress and mobilization of adequate “fight-or-flight” responses is key for survival and health. Previous studies have shown that exposure of Caenorhabditis elegans to pathogens or toxins simultaneously stimulates cellular stress and detoxification responses and aversive behavior. However, whether a coordinated regulation exists between cytoprotective stress responses and behavioral defenses remains unclear. Results Here, we show that exposure of C. elegans to high concentrations of naturally attractive food-derived odors, benzaldehyde and diacetyl, induces toxicity and food avoidance behavior. Benzaldehyde preconditioning activates systemic cytoprotective stress responses involving DAF-16/FOXO, SKN-1/Nrf2, and Hsp90 in non-neuronal cells, which confer both physiological (increased survival) and behavioral tolerance (reduced food avoidance) to benzaldehyde exposure. Benzaldehyde preconditioning also elicits behavioral cross-tolerance to the structurally similar methyl-salicylate, but not to the structurally unrelated diacetyl. In contrast, diacetyl preconditioning augments diacetyl avoidance, weakens physiological diacetyl tolerance, and does not induce apparent molecular defenses. The inter-tissue connection between cellular and behavioral defenses is mediated by JNK-like stress-activated protein kinases and the neuropeptide Y receptor NPR-1. Reinforcement of the stressful experiences using spaced training forms stable stress-specific memories. Memory retrieval by the olfactory cues leads to avoidance of food contaminated by diacetyl and context-dependent behavioral decision to avoid benzaldehyde only if there is an alternative, food-indicative odor. Conclusions Our study reveals a regulatory link between conserved cytoprotective stress responses and behavioral avoidance, which underlies “fight-or-flight” responses and facilitates self-protection in real and anticipated stresses. These findings imply that variations in the efficiency of physiological protection during past episodes of stress might shape current behavioral decisions. Graphical abstract

The PKCγ neurons in anterior cingulate cortex contribute to the development of neuropathic allodynia and pain-related emotion

Background While the PKCγ neurons in spinal dorsal horn play an indispensable part in neuropathic allodynia, the exact effect of PKCγ neurons of brain regions in neuropathic pain remains elusive. Mounting research studies have depicted that the anterior cingulate cortex (ACC) is closely linked with pain perception and behavior, the present study was designed to investigate the contribution of PKCγ neurons in ACC to neuropathic allodynia and pain-related emotion in newly developed Prkcg-P2A-Tdtomato mice. Methods The c-fos expression in response to innocuous stimulation was used to monitor the activity of PKCγ in CCI (chronic constriction injury of the sciatic nerve) induced neuropathic pain condition. Activating or silencing ACC PKCγ neurons by chemogenetics was applied to observe the changes of pain behavior. The excitability of ACC PKCγ neurons in normal and CCI mice was compared by patch-clamp whole-cell recordings. Results The PKCγ-Tdtomato neurons were mainly distributed in layer III-Vof ACC. The Tdtomato was mainly expressed in ACC pyramidal neurons demonstrated by intracellular staining. The c-fos expression in ACC PKCγ neurons in response to innocuous stimulation was obviously elevated in CCI mice. The patch clamp recordings showed that ACC PKCγ-Tdtomato neurons were largely activated in CCI mice. Chemogenetic activation of ACC PKCγ neurons in Prkcg-icre mice induced mechanical allodynia and pain-related aversive behavior, conversely, silencing them in CCI condition significantly reversed the mechanical allodynia and pain-related place aversive behavior. Conclusion We conclude that the PKCγ neurons in ACC are closely linked with neuropathic allodynia and pain-related emotional behaviors.