A Pusher and a Clip Applied to Hind Paws Under Isoflurane Sedation to Evaluate Neuropathic Pain in a CCI Model

: Rodent behavior assessments have been developed to evaluate pain. However, their fidgety activity and reactivity to human contact make it hard to activate animals in a consistent manner and get uniform and trustworthy responses. The present study was performed on prairie voles (aged 8 weeks). Sham (7 male prairie voles) and chronic constriction injury (CCI) (8 male prairie voles) rodents were investigated before surgery and four and seven days later. Each animal was assessed for nociceptive behavior. Pressure and mechanical threshold tests were conducted by the application of three different pushers to the center of hind paws and arterial clips to the toes while sedated with isoflurane. The CCI affected right lower extremity prominently increased nociceptive behavior scores four and seven days after the experiment, and the CCI affected right hind paw prominently decreased pressure and mechanical threshold tests four and seven days after the experiment . The pressure and mechanical thresholds were relevant to the scorings of nociceptive behavior in CCI model animals.

A vibrissa pathway that activates the limbic system

Vibrissa sensory inputs play a central role in driving rodent behavior. These inputs transit through the sensory trigeminal nuclei, which give rise to the ascending lemniscal and paralemniscal pathways. While lemniscal projections are somatotopically mapped from brain stem to cortex, those of the paralemniscal pathway are more widely distributed. Yet the extent and topography of paralemniscal projections are unknown, along with the potential role of these projections in controlling behavior. Here we used viral tracers to map paralemniscal projections. We find that this pathway broadcasts vibrissa-based sensory signals to brain stem regions that are involved in the regulation of autonomic functions and to forebrain regions that are involved in the expression of emotional reactions. We further provide evidence that GABAergic cells of the Kölliker-Fuse nucleus gate trigeminal sensory input in the paralemniscal pathway via a mechanism of presynaptic or extrasynaptic inhibition.

Altering Perceived Context: Transportation Cues Influence Novelty-Induced Context Exploration

Context is the milieu in which everything occurs. Many research studies consider context, or even explicitly manipulate it; yet it remains challenging to characterize. We know that a context surrounds and influences tasks; however, the boundaries of its influence are difficult to define. In behavioral science, context is often operationalized by the physical environment in which the experiment takes place, and the boundaries of the context are assumed to begin at the entrance to that of the room or apparatus. Experiences during transportation to the testing space have been shown to impact rodent behavior and memory, but transportation’s relationship with novelty and physical environment is not fully understood. The current study explored how familiar vs. novel cues, both within a physical environment and preceding it, impact the perception of a context. We manipulated context on three levels: physical testing environment, object cues within that environment, and transportation cues preceding entrance to the testing environment. We found that novel transportation cues can change rats’ perception of both familiar and novel contexts. The effects of transportation on perceived context may be affected by the length of the retention interval, testing environment, and behavioral range. These data suggest that context is a broad concept that includes cues across time and is sensitive to small differences in experience.

Effects of a 33-sequential beam galactic cosmic ray analog on male mouse behavior and evaluation of CDDO-EA as a radiation countermeasure

In long-term spaceflight, astronauts will face unique cognitive loads and social challenges which will be complicated by communication delays with Earth. It is important to understand the central nervous system (CNS) effects of deep spaceflight and the associated unavoidable exposure to galactic cosmic radiation (GCR). Rodent studies show single- or simple-particle combination exposure alters CNS endpoints, including hippocampal-dependent behavior. An even better Earth-based simulation of GCR is now available, including 33-beam GCR (33-GCR) exposure. However, the effect of whole-body 33-GCR exposure on rodent behavior is unknown, and no 33-GCR CNS countermeasures have been tested. Here astronaut-age-equivalent (6mo-old) C57BL/6J male mice were exposed to a 33-GCR (75cGy, a Mars mission dose). Pre-/during/post-Sham or 33-GCR exposure, mice were given a diet containing a "vehicle" formulation or the antioxidant/anti-inflammatory compound CDDO-EA as a potential countermeasure. Behavioral testing beginning 4mo post-irradiation suggested radiation and diet did not affect measures of exploration/anxiety-like behaviors (open field, elevated plus maze) or recognition of a novel object. However, in 3-Chamber Social Interaction (3-CSI), CDDO-EA/33-GCR mice failed to spend more time exploring a holder containing a stranger mouse vs. nothing, suggesting sociability deficits, and Vehicle/33-GCR and CDDO-EA/Sham mice failed to discriminate between a stranger vs. familiar mouse, suggesting social memory deficits. CDDO-EA given pre-/during/post-irradiation did not attenuate the 33-GCR-induced social memory deficits. Future elucidation of the mechanisms underlying 33-GCR-induced social memory deficits will improve risk analysis for astronauts which may in-turn improve countermeasures.

Adaptable and Automated Rodent Behavior Maze System

Mazes are a fundamental and widespread tool in behavior and systems neuroscience research in rodents. However, their form and inflexibility often restrict potential experimental paradigms that involve multiple or adaptive maze designs. Unique layouts often cost substantial engineering and time investments from trainee scientists. To alleviate these issues, we have developed an automated modular maze system that is flexible and scalable. This system will allow for experiments with multiple track configurations in rapid succession. Additionally, the flexibility can expedite prototyping of behaviors. Finally, the standardized componentry enhances experimental reproducibility and repeatability. This maze system presents advantages over current maze options and can facilitate novel behavior and systems neuroscience research.

Standardized and reproducible measurement of decision-making in mice

Progress in science requires standardized assays whose results can be readily shared, compared, and reproduced across laboratories. Reproducibility, however, has been a concern in neuroscience, particularly for measurements of mouse behavior. Here, we show that a standardized task to probe decision-making in mice produces reproducible results across multiple laboratories. We adopted a task for head-fixed mice that assays perceptual and value-based decision making, and we standardized training protocol and experimental hardware, software, and procedures. We trained 140 mice across seven laboratories in three countries, and we collected 5 million mouse choices into a publicly available database. Learning speed was variable across mice and laboratories, but once training was complete there were no significant differences in behavior across laboratories. Mice in different laboratories adopted similar reliance on visual stimuli, on past successes and failures, and on estimates of stimulus prior probability to guide their choices. These results reveal that a complex mouse behavior can be reproduced across multiple laboratories. They establish a standard for reproducible rodent behavior, and provide an unprecedented dataset and open-access tools to study decision-making in mice. More generally, they indicate a path toward achieving reproducibility in neuroscience through collaborative open-science approaches.

Involvement of Opioid System and TRPM8/TRPA1 Channels in the Antinociceptive Effect of Spirulina platensis

Spirulina platensis is a “super-food” and has attracted researchers’ attention due to its anti-inflammatory, antioxidant, and analgesic properties. Herein, we investigated the antinociceptive effects of Spirulina in different rodent behavior models of inflammatory pain. Male Swiss mice were treated with Spirulina (3–300 mg/kg, p.o.), indomethacin (10 mg/kg, p.o.), or vehicle (0.9% NaCl 10 mL/kg). Behavioral tests were performed with administration of acetic acid (0.6%, i.p.), formalin 2.7% (formaldehyde 1%, i.pl.), menthol (1.2 µmol/paw, i.pl.), cinnamaldehyde (10 nmol/paw, i.pl.), capsaicin (1.6 µg/paw, i.pl.), glutamate (20 µmol/paw, i.pl.), or naloxone (1 mg/kg, i.p.). The animals were also exposed to the rotarod and open field test to determine possible effects of Spirulina on locomotion and motor coordination. The quantitative phytochemical assays exhibited that Spirulina contains significant concentrations of total phenols and flavonoid contents, as well as it showed a powerful antioxidant effect with the highest scavenging activity. Oral administration of Spirulina completely inhibited the abdominal contortions induced by acetic acid (ED50 = 20.51 mg/kg). Spirulina treatment showed significant inhibition of formalin-induced nociceptive behavior during the inflammatory phase, and the opioid-selective antagonist markedly blocked this effect. Furthermore, our data indicate that the mechanisms underlying Spirulina analgesia appear to be related to its ability to modulate TRMP8 and TRPA1, but not by TRPV1 or glutamatergic system. Spirulina represents an orally active and safe natural analgesic that exhibits great therapeutic potential for managing inflammatory pain disorders.

Corticotropin Releasing Hormone Signaling in the Bed Nuclei of the Stria Terminalis as a Link to Maladaptive Behaviors

The bed nuclei of the stria terminalis (BST) is a limbic region in the extended amygdala that is heavily implicated in anxiety processing and hypothalamic-adrenal-pituitary (HPA) axis activation. The BST is complex, with many nuclei expressing different neurotransmitters and receptors involved in a variety of signaling pathways. One neurotransmitter that helps link its functions is corticotropin releasing hormone (CRH). BST CRH neuron activation may cause both anxiogenic and anxiolytic effects in rodents, and CRH neurons interact with other neuron types to influence anxiety-like responses as well as alcohol and drug–seeking behavior. This review covers the link between BST CRH neurons and thirteen other neurotransmitters and receptors and analyzes their effect on rodent behavior. Additionally, it covers the translational potential of targeting CRH signaling pathways for the treatment of human mental health disorders. Given the massive impact of anxiety, mood, and substance use disorders on our society, further research into BST CRH signaling is critical to alleviate the social and economic burdens of those disorders.