The inbred Roman rat strains, which have been selected and bred for their very high (RHA) or extremely poor (RLA) ability to acquire the two-way active avoidance task, constitute a bidirectional genetic model in which each strain differs from the other and/or from "standard" laboratory rat strains in a large number of behavioral and neurobiological phenotypes. Relative to Roman low-avoidance (RLA) rats, the Roman High-avoidance (RHA) rats exhibit increased mesolimbic dopamine function, social deficits, and impaired attention and cognitive flexibility, besides many other neurobehavioral phenotypes that make them a promising animal model of attention/cognitive-related syndromes, such as schizophrenia or attention deficit/hyperactivity disorder (ADHD). This study aimed to investigate non-spatial working memory and long-term memory in the Roman rat strains using the Object Recognition Test (ORT), a non-spatial declarative memory task that assesses object memory encoding, consolidation, and retrieval. The Object Location Test (OLT), which measures recognition of object location rather than differences between objects, was also used to evaluate short- and long-term memory. Between-strain spatial working memory differences were also evaluated using a delayed-matching-to-place (DMTP) task in the Morris water maze. Findings showed that RHA rats exhibited impaired working memory and long-term memory compared to RLA rats in the ORT. The degree of previous habituation to the testing context significantly affected object recognition memory in RHA rats. RHA rats also exhibited impaired short-term memory in the OLT. In the DMTP task, spatial working memory was also impaired in RHAs. The memory deficits shown by RHA rats seem to be compatible with their known (schizophrenia-like) alterations of the hippocampus and prefrontal cortex. The finding that relatively long habituation to the testing context rescues the long-term object-recognition memory deficit of RHA rats suggests that impaired attention, perhaps related to their relative hyperactivity, might be a factor underlying that deficit. The findings of the present study support the notion that the inbred RHA rat strain presents impairments in both non-spatial and spatial working/short-term memory, aligning with cognitive symptoms observed in patients with schizophrenia or with ADHD.

Animals rely on associative spatial memory to navigate toward previously learned, reward-associated goals. This reward-guided navigation is supported by the hippocampus and its interactions with cortical and subcortical regions: processes which are vital for integrating sensory cues and forming experience-dependent associations. In adulthood, hippocampal-dependent information processing is shaped by aging, reflecting changes in synaptic plasticity and neuromodulatory support. In parallel, mice with distinct genetic backgrounds show systematic differences in behavior, sensory function, and hippocampal plasticity. How mouse strain and age interact to affect spatial appetitive memories has not been well defined. Here, we trained juvenile (2-3 months) and mature (7-8 months) adult CBA/CaOlaHsd and C57BL/6 mice in daily training events, to perform a T-maze task with rewards available at a fixed location and decreasing probability in one maze arm. The task consisted of an initial deterministic phase in which a correct response was always rewarded, followed by a probabilistic phase during which reward omissions became increasingly prevalent. We measured correct choices, as well as latencies across training blocks, and combined trial-by-trial metrics with reinforcement learning modeling to assess decision strategies. We observed that CBA/CaOlaHsd mice displayed lower choice latencies than C57BL/6 mice, reached high performance earlier, and maintained better performance when the reward probability decreased. Age was associated with higher latencies and modulated both performance and decision policies in a strain-dependent manner. Moreover, CBA/CaOlaHsd mice displayed higher learning rates from positive outcomes and adopted strategies consistent with more robust context exploitation under uncertainty. C57BL/6 mice, by contrast, exhibited stronger omission-driven strategy switching compared to CBA/CaOlaHsd mice. Together, these findings reveal robust strain- and age-dependent differences in trial-by-trial decision policies and spatial learning performance.

Xenopus laevis has long served as an important model for studies of embryonic development and is a cornerstone to our current understanding of cellular and molecular mechanisms underlying neurodevelopment, including the formation and refinement of neural circuits. In recent years, considerable efforts have been made to leverage the great accessibility and amenability of the Xenopus system to model neurodevelopmental and neurodegenerative disorders in humans for higher-throughput investigations of genetic and environmental risk factors. Behavioral paradigms are indispensable tools to assess functional output in whole animals. In this review, we summarize a range of behavioral paradigms established in Xenopus laevis and Xenopus tropicalis tadpoles to evaluate the functional development of the nervous system. We discuss the current understanding of neural substrates that give rise to specific behaviors, and how these paradigms have been used to evaluate the functional ramifications of cellular and molecular abnormalities in neural circuitry. We cover three categories of behavioral paradigms: innate and stable behaviors, experience-dependent and learned behaviors, and social behaviors. Each provides distinct functional readouts of the developing nervous system. We also include tips and suggestions for the implementation of these paradigms and discuss how insights from other aquatic animal models may inform the further development of behavioral paradigms in Xenopus tadpoles.

Pavlovian-Instrumental Transfer (PIT) exemplifies how Pavlovian-motivational influences modulate goal-directed behavior, yielding outcome-specific (specific PIT) and general (general PIT) transfer. General PIT is commonly interpreted as outcome-general invigoration and is sensitive to stress. However, human PIT research typically uses visual, appetitive procedures, whereas rodent PIT research often uses auditory cues, limiting translation. We tested whether cue modality, along with additional factors such as immersive threat contexts, modulates PIT, and whether virtual reality (VR) enhances general transfer.

Transcranial alternating current stimulation (tACS) has emerged as a promising tool to modulate cognitive functions by entraining endogenous neural oscillations. This study investigated the behavioral and neurophysiological after-effects of theta-frequency tACS individualized to each participant's intrinsic theta frequency (ITF).

False contextual fear memory has been attributed to a time-dependent loss of precision in contextual memory representations. In this study, we investigated the role of protein kinase M zeta (PKMζ), a key molecule in the maintenance of hippocampus-dependent long-term memory, in false contextual fear memory within the dorsal (dHPC) and ventral hippocampus (vHPC).

Early-life social experiences have a profound impact on the development of the brain and behavior. Previous work has shown that prairie voles (Microtus ochrogaster) raised in a socially limited environment (raised by a single mother and isolated after weaning) engaged in more social behaviors compared to those raised in a socially enriched environment (raised biparentally and group-housed after weaning). Furthermore, intranasal oxytocin has been therapeutically used in children, yet little is known about how this might affect brain development. Oxytocin is a crucial neuropeptide involved in social behavior and cognition, and variation in parental care and early social experiences has the potential to alter oxytocin receptors (OTR) throughout the brain. However, few studies have asked how different social experiences interact to alter brain phenotype.

Wiskott-Aldrich syndrome protein family member 1 (WASF1) truncating variants, such as c.1516C>T (p.Arg506Ter), are established causes of neurodevelopmental disorders (NDDs), but their underlying pathogenic mechanism remains debated. This study aimed to clarify the disease mechanism and identify potential therapeutic leads.

Stimulant use disorders are chronic relapsing conditions that differentially affect men and women. Growing evidence has demonstrated that endocrine systems play critical, bidirectional roles in regulating vulnerability to drug use, escalation, withdrawal, and relapse, particularly for women. In the current review we discuss the bidirectional relation between gonadal hormones; focusing on estradiol (E2), progesterone (P4), and testosterone (T); and stimulant rewards and reinforcement; focusing on cocaine, amphetamine, and methamphetamine. Most research to date has focused on cocaine and less so on amphetamine or methamphetamine. Similarly, most research has been conducted with rodents and less so with nonhuman primates and humans. Collectively, the literature supports stimulant misuse as an endocrine disorder, particularly for females, emerging from reciprocal interactions between neural and hormone systems. The reciprocal relation between gonadal hormones and stimulant rewards and reinforcement is, for the most part, reliable and robust in female rodents; however, the relation is somewhat mixed with female nonhuman primates and women. These mixed results likely are a result of the wide within- and between-subject variability in menstrual cycles (i.e., duration) and levels of ovarian hormones (e.g., E2 and P4 levels) in female nonhuman primates and women. Additionally, it is impossible to determine complete menstrual cycles prior to stimulant exposure in women as it is in female rats or nonhuman primates, though determination of menstrual cycles prior to stimulant exposure with female nonhuman primates is sparse. Female rodents, on the other hand, have much less variability in estrous cycles and corresponding E2 and P4 levels, and complete estrous cycles and hormone levels are easily obtainable prior to stimulant exposure. Finally, while the reciprocal relation between gonadal hormones and stimulants in males and men has been studied, the relation appears to be less reliably implicated in stimulant rewards and reinforcement compared with females, women, and ovarian hormones. Recognizing the hypothalamic-pituitary-gonadal (HPG) axis, including effects of stimulants on gonadal hormones and vice versa, is critical for developing individualized pharmacotherapies for stimulant misuse, particularly for women, and for understanding sex-specific stimulant-misuse phenotypes.

Traumatic brain injury (TBI) is a major health concern in the current population. Animal models are increasingly important for identifying early neurobehavioural changes associated with mild to severe as well as repetitive brain injuries. In this study, we analysed behavioural changes in a mouse model of repetitive mild TBI using unbiased quantification metrics. Our approach enabled automated markerless pose estimation of thigmotaxis together with spatial working memory and locomotor activity assessments specifically during the scarcely-studied subacute phase after brain injury. We found that animals exposed to repetitive mild head impacts developed anxiety-like behaviour, manifested by avoidance of the central zone and increased thigmotaxis in the open field test, while maintaining total distance travelled compared to the control group. However, analysis of exploratory behaviour and spatial working memory in the Y-maze, along with assessment of sensorimotor coordination and balance using rotarod tests, revealed no significant difference between the TBI and control groups. These findings suggest that repetitive mTBI is associated with selective anxiety-like behaviour during the subacute phase after brain injury, without detectable motor or cognitive deficits, reflecting the early affective symptomatology frequently reported in clinical populations with mTBI.