Global Cerebral Ischemia in Male Long Evans Rats Impairs Dopaminergic/ΔFosB Signalling in the Mesocorticolimbic Pathway Without Altering Delay Discounting Rates

Global cerebral ischemia (GCI) in rats has been shown to promote exploration of anxiogenic zones of the Elevated-Plus Maze (EPM) and Open Field Test (OFT). This study investigated changes in impulsive choice and/or defensive responses as possible contributors of heightened anxiogenic exploration observed after ischemia. Impulsivity was assessed using delay discounting (DD) paradigms, while the Predator Odour Test (PO) served to assess changes in defensive responses towards a naturally aversive stimulus. Male Long Evans rats underwent 9 days of autoshaping training and 24 days of DD training prior to GCI or sham surgery (n = 9/group). Post-surgery, rats completed the OFT, EPM, and PO, followed by 6 days of DD sessions. Blood droplets served to evaluate corticosterone secretion associated with PO exposure. With impulsivity being regulated through mesocorticolimbic monoaminergic pathways, we also characterised post-ischemic changes in the expression of dopamine D2 receptors (DRD2), dopamine transporters (DAT), and 1FosB in the basolateral amygdala (BLA), nucleus accumbens core (NAcC) and shell (NAcS), and ventromedial prefrontal cortex (vmPFC) using immunohistofluorescence. Our findings revealed no impact of GCI on delay discounting rates, while PO approach behaviours were minimally affected. Nonetheless, GCI significantly reduced DRD2 and ΔFosB-ir in the NAcS and NAcC, respectively, while DAT-ir was diminished in both NAc subregions. Collectively, our findings refine the understanding of cognitive-behavioural and biochemical responses following stroke or cardiac arrest. They support significant alterations to the dopaminergic mesocorticolimbic pathway after ischemia, which are not associated with altered impulsive choice in a DD task but may influence locomotor exploration of the OFT and EPM.

Open biological negative image set

Scientists conducting affective research often use visual, emotional images, to examine the mechanisms of defensive responses to threatening and dangerous events and objects. Many studies use the rich emotional images from the International Affective Picture System (IAPS) to facilitate affective research. While IAPS images can be classified into emotional categories such as fear or disgust, the number of images per discrete emotional category is limited. We developed the Open Biological Negative Image Set (OBNIS) consisting of 200 colour and greyscale creature images categorized as disgusting, fearful or neither. Participants in Experiment 1 ( N = 210) evaluated the images' valence and arousal and classified them as disgusting , fearful or neither. In Experiment 2, other participants ( N = 423) rated the disgust and fear levels of the images. As a result, the OBNIS provides valence, arousal, disgust and fear ratings and ‘disgusting,’ 'fearful' and ‘neither’ emotional categories for each image. These images are available to download on the Internet ( https://osf.io/pfrx4/?view_only=911b1be722074ad4aab87791cb8a72f5 ).

Human iPSC-Derived Astrocytes: A Powerful Tool to Study Primary Astrocyte Dysfunction in the Pathogenesis of Rare Leukodystrophies

Astrocytes are very versatile cells, endowed with multitasking capacities to ensure brain homeostasis maintenance from brain development to adult life. It has become increasingly evident that astrocytes play a central role in many central nervous system pathologies, not only as regulators of defensive responses against brain insults but also as primary culprits of the disease onset and progression. This is particularly evident in some rare leukodystrophies (LDs) where white matter/myelin deterioration is due to primary astrocyte dysfunctions. Understanding the molecular defects causing these LDs may help clarify astrocyte contribution to myelin formation/maintenance and favor the identification of possible therapeutic targets for LDs and other CNS demyelinating diseases. To date, the pathogenic mechanisms of these LDs are poorly known due to the rarity of the pathological tissue and the failure of the animal models to fully recapitulate the human diseases. Thus, the development of human induced pluripotent stem cells (hiPSC) from patient fibroblasts and their differentiation into astrocytes is a promising approach to overcome these issues. In this review, we discuss the primary role of astrocytes in LD pathogenesis, the experimental models currently available and the advantages, future evolutions, perspectives, and limitations of hiPSC to study pathologies implying astrocyte dysfunctions.

Modelling Artificial Immunization Processes to Counter Cyberthreats

This paper looks at the problem of cybersecurity in modern cyber-physical and information systems and proposes an immune-like approach to the information security of modern complex systems. This approach is based on the mathematical modeling in information security—in particular, the use of immune methods to protect several critical system nodes from a predetermined range of attacks, and to minimize the success of an attack on the system. The methodological approach is to systematize the tasks, means and modes of immunization to describe how modern systems can counter the spread of computer attacks. The main conclusions and recommendations are that using an immunization approach will not only improve the security of systems, but also define principles for building systems that are resistant to cyber attacks. The immunization approach enables a symmetrical response to an intruder in a protected system to be produced rapidly. This symmetry provides a step-by-step neutralization of all stages of a cyber attack, which, combined with the accumulation of knowledge of the attacker’s actions, allows a base of defensive responses to be generated for various cyber attack scenarios. The theoretical conclusions are supported by practical experiments describing real-world scenarios for the use of immunization tools to protect against cyber threats.

Help or flight: Neural defensive circuits promote helping under threat in humans

Helping of conspecifics under threat has been observed across species. In humans, the dominant view proposes that empathy is the key proximal mechanism driving helping motivation in a threatening context, but little is known about how one s own defensive responses to the threat may guide helping decisions. In this pre-registered study, we manipulated threat imminence to activate the entire defensive brain circuitry, and assess the impact of different defensive responses on risky helping behaviour. Forty-nine participants underwent fMRI scanning while making trial-by-trial decisions about whether or not to help a co-participant avoid aversive shocks at the risk of receiving a shock themselves. Helping decisions were prompted under imminent and distal threat, based on the spatiotemporal distance to the administration of the shock to the co-participant. We found that greater engagement of reactive fear circuits (insula, ACC, PAG) during the threat presentation led to helping decisions, whereas engagement of cognitive fear circuits (hippocampus and vmPFC) preceded decisions not to help. Relying on representational similarity analysis, we identified how the defensive circuitry uniquely represented the threat to oneself, and the distress of the co-participant during the task. Importantly, we found that the strength with which the amygdala represented the threat to oneself, and not the other s distress, predicted decisions to help. Our results demonstrate that defensive neural circuits coordinating fast escape from immediate danger may also facilitate decisions to help others, potentially by engaging neurocognitive systems implicated in caregiving across mammals. Taken together, our findings provide novel insights into the proximal basis of altruistic responding, suggesting that defensive responses may play a more important role in helping than previously understood.

Neural correlates and determinants of approach-avoidance conflict in the prelimbic prefrontal cortex

The recollection of environmental cues associated with threat or reward allows animals to select the most appropriate behavioral responses. Neurons in the prelimbic cortex (PL) respond to both threat- and reward-associated cues. However, it remains unknown whether PL regulates threat-avoidance vs. reward-approaching responses when an animals' decision depends on previously associated memories. Using a conflict model in which male Long-Evans rats retrieve memories of shock- and food-paired cues, we observed two distinct phenotypes during conflict: i) rats that continued to press a lever for food (Pressers); and ii) rats that exhibited a complete suppression in food seeking (Non-pressers). Single-unit recordings revealed that increased risk-taking behavior in Pressers is associated with persistent food-cue responses in PL, and reduced spontaneous activity in PL glutamatergic (PLGLUT) neurons during conflict. Activating PLGLUT neurons in Pressers attenuated food-seeking responses in a neutral context, whereas inhibiting PLGLUT neurons in Non-pressers reduced defensive responses and increased food approaching during conflict. Our results establish a causal role for PLGLUT neurons in mediating individual variability in memory-based risky decision making by regulating threat-avoidance vs. reward-approach behaviors.

Conditional Freezing, Flight and Darting?

Fear conditioning is one of the most frequently used laboratory procedures for modeling learning and memory generally, and anxiety disorders in particular. The conditional response (CR) used in the majority of fear conditioning studies in rodents is freezing. Recently, it has been reported that under certain conditions, running, jumping or darting replaces freezing as the dominant CR. These findings raise both a critical methodological problem and an important theoretical issue. If only freezing is measured but rodents express their learning with a different response, then significant instances of learning, memory, or fear may be missed. In terms of theory, whatever conditions lead to these different behaviors may be a key to how animals transition between different defensive responses and different emotional states. We replicated these past results but along with several novel control conditions. Contrary to the prior conclusions, running and darting were entirely a result of nonassociative processes and were actually suppressed by associative learning. Darting and flight were taken to be analogous to nonassociative startle or alpha responses that are potentiated by fear. On the other hand, freezing was the purest reflection of associative learning. We also uncovered a rule that describes when these movements replace freezing: When afraid, freeze until there is a sudden novel change in stimulation, then burst into vigorous flight attempts. This rule may also govern the change from fear to panic.

Designing anti-predator training to maximize learning and efficacy assessments

Despite the growing need to use conservation breeding and translocations in species’ recovery, many attempts to reintroduce animals to the wild fail due to predation post-release. Released animals often lack appropriate behaviours for survival, including anti-predator responses. Anti-predator training—a method for encouraging animals to exhibit wariness and defensive responses to predators—has been used to help address this challenge with varying degrees of success. The efficacy of anti-predator training hinges on animals learning to recognize and respond to predators, but learning is rarely assessed, or interventions miss key experimental controls to document learning. An accurate measure of learning serves as a diagnostic tool for improving training if it otherwise fails to reduce predation. Here we present an experimental framework for designing anti-predator training that incorporates suitable controls to infer predator-specific learning and illustrate their use with the critically endangered Hawaiian crow, ‘alalā (Corvus hawaiiensis). We conducted anti-predator training within a conservation breeding facility to increase anti-predator behaviour towards a natural predator, the Hawaiian hawk, ‘io (Buteo solitaries). In addition to running live-predator training trials, we included two control groups, aimed at determining if responses could otherwise be due to accumulated stress and agitation, or to generalized increases in fear of movement. We found that without these control groups we may have wrongly concluded that predator-specific learning occurred. Additionally, despite generations in human care that can erode anti-predator responses, ‘alalā showed unexpectedly high levels of predatory wariness during baseline assessments. We discuss the implications of a learning-focused approach to training for managing endangered species that require improved behavioural competence for dealing with predatory threats, and the importance of understanding learning mechanisms in diagnosing behavioural problems.

‘Cause We’re All Just Part of the System Really’: Complicity and Resistance in Young Sportsmen’s Responses to Violence Against Women Prevention Campaigns in England

In recent years, initiatives to prevent men’s violence against women on university campuses in England have been growing. However, there remains a lack of institutional recognition about the gendered dynamics of this abuse and the importance of engaging men in ending it. This research sought to shed light on how young men make sense of violence prevention campaigns, through eight focus groups with 45 members of men’s university sports teams. The focus groups illustrated the need for prevention work to expand men’s critical consciousness of complicity in violence against women, to encourage them to reflect on both their personal connections to the problem and the positive role they can play in preventing it. This complicity was at times exhibited within the focus groups themselves, such as in defensive responses when patriarchal privileges and norms were brought into question. These included shifting the focus away from men’s violence and onto men’s victimisation, naturalisations of partner violence as an inevitability, and disassociating from the problem as if it was separate from the participants’ lives. Collective masculine norms appeared to play a substantial role in shaping the discussions, illustrating how these can mediate young men’s responses to prevention campaigns. However, at times the participants did challenge sexism among one another and articulate resistance to men’s violence against women, demonstrating their capacity to create change. The article contends that violence prevention requires critically addressing men’s practices and what Hearn calls the ‘hegemony of men’ more broadly, rather than only problematising specific ‘forms’ of masculinities.