Large nesting expression in deer mice remains stable under conditions of visual deprivation despite heightened limbic involvement: Perspectives on compulsive-like behavior.

Visual stimuli and limbic activation varyingly influence obsessive-compulsive symptom expression and so impact treatment outcomes. Some symptom phenotypes, for example, covert repugnant thoughts, are likely less sensitive to sensory stimuli compared to symptoms with an extrinsic focus, that is, symptoms related to contamination, safety, and "just-right-perceptions." Toward an improved understanding of the neurocognitive underpinnings of obsessive-compulsive psychobiology, work in naturalistic animal model systems is useful. Here, we explored the impact of visual feedback and limbic processes on 24 normal (NNB) and large (LNB) nesting deer mice, respectively (as far as possible, equally distributed between sexes). Briefly, after behavioral classification into either the NNB or LNB cohorts, mice of each cohort were separated into two groups each and assessed for nesting expression under either standard light conditions or conditions of complete visual deprivation (VD). Nesting outcomes were assessed in terms of size and neatness. After nesting assessment completion, mice were euthanized, and samples of frontal-cortical and hippocampal tissues were collected to determine serotonin and noradrenaline concentrations. Our results show that LNB, as opposed to NNB, represents an inflexible and excessive behavioral phenotype that is not dependent on visually guided action-outcome processing, and that it associates with increased frontal-cortical and hippocampal noradrenaline concentrations, irrespective of lighting condition. Collectively, the current results are informing of the neurocognitive underpinnings of nesting behavior. It also provides a valuable foundation for continued investigations into the noradrenergic mechanisms that may influence the development and promulgation of excessive, rigid, and inflexible behaviors.

Behavioral effects of chronic stress in Carioca high- and low-conditioned freezing rats.

Chronic unpredictable mild stress (CUMS) is a widely used model to study stress-coping strategies in rodents. Different factors have been shown to influence whether animals adopt passive or active coping responses to CUMS. Individual adaptation and susceptibility to the environment seem to play a critical role in this process. To further investigate this relationship, we examined the effects of CUMS on Carioca high- and low-conditioned freezing rats (CHF and CLF, respectively), bidirectional lines of animals selected for high and low freezing in response to contextual cues that were previously associated with footshocks. For this purpose, the behavior of CHF and CLF animals was evaluated in the contextual fear conditioning, open field, elevated T maze, and forced swimming tests before and after 21 days of CUMS. For all tests, CHF rats were more susceptible to the effects of CUMS compared to CLF. CHF animals exposed to CUMS displayed a reduction in freezing behavior, decreased number of entries and time spent in the center of the open field, greater latencies to become immobile, and increased avoidance and escaping behaviors in the elevated T maze. Overall, these findings support the hypothesis that a heightened susceptibility to the environment exerts a strong influence on coping responses to chronic stress.

Theoretical, and epistemological challenges in scientific investigations of complex emotional states in animals.

This review brings to light critical epistemological and theoretical considerations when studying complex emotional states in animals. We discuss anthropomorphic and Umwelt perspectives of nonhuman animals and the ways in which distinct theories of consciousness and neural processing may restrict the potential for the development of knowledge on the topic. Within the same line of argumentation, we consider influences of the debate between monism and dualism and psychology's behaviorism and cognitive theories. Finally, we contrast the affective consciousness, higher-order emotional consciousness, and constructed emotion theories to further our understanding of complex emotional states in animals.

Retinal and Tectal "Driver-Like" Inputs Converge in the Shell of the Mouse Dorsal Lateral Geniculate Nucleus.

The dorsal lateral geniculate nucleus (dLGN) is a model system for understanding thalamic organization and the classification of inputs as "drivers" or "modulators." Retinogeniculate terminals provide the primary excitatory drive for the relay of information to visual cortex (V1), while nonretinal inputs act in concert to modulate the gain of retinogeniculate signal transmission. How do inputs from the superior colliculus, a visuomotor structure, fit into this schema? Using a variety of anatomical, optogenetic, and in vitro physiological techniques in mice, we show that dLGN inputs from the superior colliculus (tectogeniculate) possess many of the ultrastructural and synaptic properties that define drivers. Tectogeniculate and retinogeniculate terminals converge to innervate one class of dLGN neurons within the dorsolateral shell, the primary terminal domain of direction-selective retinal ganglion cells. These dLGN neurons project to layer I of V1 to form synaptic contacts with dendrites of deeper-layer neurons. We suggest that tectogeniculate inputs act as "backseat drivers," which may alert shell neurons to movement commands generated by the superior colliculus. Significance statement: The conventional view of the dorsal lateral geniculate nucleus (dLGN) is that of a simple relay of visual information between the retina and cortex. Here we show that the dLGN receives strong excitatory input from both the retina and the superior colliculus. Thus, the dLGN is part of a specialized visual channel that provides cortex with convergent information about stimulus motion and eye movement and positioning.

Absence of plateau potentials in dLGN cells leads to a breakdown in retinogeniculate refinement.

The link between neural activity and the refinement of projections from retina to the dorsal lateral geniculate nucleus (dLGN) of thalamus is based largely on studies that disrupt presynaptic retinogeniculate activity. Postsynaptic mechanisms responsible for implementing the activity-dependent remodeling in dLGN remain unknown. We tested whether L-type Ca(2+) channel activity in the form of synaptically evoked plateau potentials in dLGN cells is needed for remodeling by using a mutant mouse that lacks the ancillary ß3 subunit and, as a consequence, has highly reduced L-type channel expression and attenuated L-type Ca(2+) currents. In the dLGNs of ß3-null mice, glutamatergic postsynaptic activity evoked by optic tract stimulation was normal, but plateau potentials were rarely observed. The few plateaus that were evoked required high rates of retinal stimulation, but were still greatly attenuated compared with those recorded in age-matched wild-type mice. While ß3-null mice exhibit normal stage II and III retinal waves, their retinogeniculate projections fail to segregate properly and dLGN cells show a high degree of retinal convergence even at late postnatal ages. These structural and functional defects were also accompanied by a reduction in CREB phosphorylation, a signaling event that has been shown to be essential for retinogeniculate axon segregation. Thus, postsynaptic L-type Ca(2+) activity plays an important role in mediating the refinement of the retinogeniculate pathway.

Retinal input regulates the timing of corticogeniculate innervation.

Neurons in layer VI of visual cortex represent one of the largest sources of nonretinal input to the dorsal lateral geniculate nucleus (dLGN) and play a major role in modulating the gain of thalamic signal transmission. However, little is known about how and when these descending projections arrive and make functional connections with dLGN cells. Here we used a transgenic mouse to visualize corticogeniculate projections to examine the timing of cortical innervation in dLGN. Corticogeniculate innervation occurred at postnatal ages and was delayed compared with the arrival of retinal afferents. Cortical fibers began to enter dLGN at postnatal day 3 (P3) to P4, a time when retinogeniculate innervation is complete. However, cortical projections did not fully innervate dLGN until eye opening (P12), well after the time when retinal inputs from the two eyes segregate to form nonoverlapping eye-specific domains. In vitro thalamic slice recordings revealed that newly arriving cortical axons form functional connections with dLGN cells. However, adult-like responses that exhibited paired pulse facilitation did not fully emerge until 2 weeks of age. Finally, surgical or genetic elimination of retinal input greatly accelerated the rate of corticogeniculate innervation, with axons invading between P2 and P3 and fully innervating dLGN by P8 to P10. However, recordings in genetically deafferented mice showed that corticogeniculate synapses continued to mature at the same rate as controls. These studies suggest that retinal and cortical innervation of dLGN is highly coordinated and that input from retina plays an important role in regulating the rate of corticogeniculate innervation.

Ontogenetic analysis of behavior in the tail suspension test: temporal differences in the emergence of within- and between-session habituation in Swiss mice.

Habituation is an important tool in the investigation of learning/memory throughout life. Despite that, few studies describe habituation from an ontogenetic perspective. Considering that, as soon as they are born, rodents can twist their bodies when lifted by their tails in an attempt to escape, this behavior should be well suited to study habituation behavior from birth to adulthood. Here, we implement a tail suspension test to study the ontogenetic development of habituation in Swiss mice. Our data indicate that a continuous within-session decrease in trunk movements can be observed from postnatal day (P) 10 onwards and that between-sessions habituation (from one day to another) can be observed from P16 onwards. Furthermore, we show that the adult pattern of within- and between-sessions reductions in activity is already present by the beginning of adolescence, at P28. Our results indicate that between-sessions habituation involves a more complex mechanism of memory and learning than within-session habituation, requiring a longer period of brain maturation before it can be displayed.

Are you how you eat? Aspects of self-awareness in eating disorders.

Eating disorders (ED) are severe psychiatric disorders characterized by dysfunctional behaviors related to eating or weight control, with profound impacts on health, quality of life, and the financial burden of affected individuals and society at large. Given that these disorders involve disturbances in self-perception, it is crucial to comprehend the role of self-awareness in their prevalence and maintenance. This literature review presents different self-awareness processes, discussing their functioning across different levels of complexity. By deconstructing this concept, we can gain a better understanding of how each facet of self and personality relates to the symptoms of these disorders. Understanding the absence or impairment of self-awareness in ED holds significant implications for diagnosis, treatment, and overall management. By recognizing and comprehending the characteristics of self-awareness, clinicians can develop tailored interventions and evidence-based treatments for individuals with ED. Furthermore, this narrative review underscores the importance of considering temperament and personality factors in the context of ED, as temperament traits and personality characteristics may interact with self-awareness processes, influencing the development and maintenance of ED. Ultimately, the results highlight the pressing need for further research on the development of effective interventions and support strategies grounded in the aspects of self-awareness mechanisms for individuals affected by these disorders.

Pharmacological and Physiological Correlates of the Bidirectional Fear Phenotype of the Carioca Rats and Other Bidirectionally Selected Lines.

The Carioca rat lines originated from the selective bidirectional breeding of mates displaying extreme defense responses to contextual conditioned fear. After three generations, two distinct populations could be distinguished: the Carioca High- and Low-conditioned Freezing rats, CHF, and CLF, respectively. Later studies identified strong anxiety-like behaviors in the CHF line, while indications of impulsivity and hyperactivity were prominent in the CLF animals. The present review details the physiological and pharmacological-related findings obtained from these lines. The results discussed here point towards a dysfunctional fear circuitry in CHF rats, including alterations in key brain structures and the serotoninergic system. Moreover, data from these animals highlight important alterations in the stress-processing machinery and its associated systems, such as energy metabolism and antioxidative defense. Finally, evidence of an alteration in the dopaminergic pathway in CLF rats is also debated. Thus, accumulating data gathered over the years, place the Carioca lines as significant animal models for the study of psychiatric disorders, especially fear-related ones like anxiety.

Combined exposure to alcohol and cannabis during development: Mechanisms and outcomes.

Exposure to substances of abuse during pregnancy can have long-lasting effects on offspring. Alcohol is one of the most widely used substances of abuse that leads to the most severe consequences. Recent studies in the United States, Canada, and the United Kingdom showed that between 1% and 7% of all children exhibit signs and symptoms of fetal alcohol spectrum disorder (FASD). Despite preventive campaigns, the rate of children with FASD has not decreased during recent decades. Alcohol consumption often accompanies exposure to such drugs as tobacco, cocaine, opioids, and cannabis. These interactions can be synergistic and exacerbate the deleterious consequences of developmental alcohol exposure. The present review focuses on interactions between alcohol and cannabis exposure and the potential consequences of these interactions.

Tracking demands for seeking psychological help before and during the COVID-19 pandemic: a quanti-qualitative study.

The COVID-19 pandemic has placed unprecedented burdens on individuals and communities around the world. The isolation, fear, and uncertainty caused by the virus has led to increased rates of anxiety, depression, and other mental health issues. The pandemic has also had a disproportionate impact on individuals and communities with low income and socioeconomic status.ObjectiveTo shed light on the consequences of the pandemic on individuals from minorities and low-income areas, we investigate the main reasons that led patients who were referred to a social clinic of a private university in Rio de Janeiro to seek psychological treatment before (2019) and during the pandemic (2020 and 2021).MethodsWe conducted a quanti-qualitative study with a lexical analysis that evaluated 549 complaint forms of patients seeking treatment in these two distinct periods. Our analyses included descending hierarchical analysis (DHA) and correspondence factor analysis (CFA).ResultsFamily dynamics and communication factors play a dominant role in the reason for seeking therapy and psychological treatment. Additionally, our study suggested an increase in anxiety and panic attacks among other mental health issues associated with grief and losses during the pandemic years.ConclusionBased on these analyses, we can begin to identify a few changes in the main demand and redirection of complaints of patients during the period of COVID-19.

Neuropsychological evaluation of children and adolescents with fetal alcohol spectrum disorders in the Brazilian population.

Fetal Alcohol Spectrum Disorder (FASD) is a collective name for lifelong physical and neurodevelopmental problems caused by the gestational consumption of alcohol affecting fetal development. In Brazil, the lack of awareness among healthcare professionals, and the scarcity of suitable diagnostic tools and trained clinicians, can contribute to the underestimation of FASD prevalence and severity. The present review aims to map and analyze studies conducted in Brazil on children and adolescents with FASD or a history of prenatal alcohol exposure (PAE). Additionally, it intends to report the psychometric properties of the neurodevelopmental assessment tools applied in the selected articles. Searches were carried out in the databases Scielo, LILACS, PePSIC, EMBASE, PsycINFO, Web of Science, selecting original clinical studies that have investigated the neurodevelopment of this population. From a total of 175 studies, ten articles fit the inclusion criteria in which 18 instruments were identified. The most reported deficits were related to language, general intelligence quotient (IQ), adaptive behavior, attention, and visual perception. Our results point to the need for more clinical research on FASD in Brazil, as well as for the standardization and validation of neurodevelopmental assessment tools for the accurate diagnosis of FASD in Brazil.

Homeostatic plasticity in the visual thalamus by monocular deprivation.

Monocular deprivation (MD) is a classic paradigm for experience-dependent cortical plasticity. One form is known as homeostatic plasticity, in which neurons innervated by the deprived eye show a remarkable capacity to compensate for degraded visual signals in an attempt to stabilize network activity. Although the evidence supporting homeostatic plasticity in visual cortex is extensive, it remains unclear whether neurons in subcortical visual structures respond to MD in a similar manner. Here we examined whether cells in the dorsal lateral geniculate nucleus (dLGN), the thalamic relay between the retina and visual cortex, show similar forms of experience-dependent homeostatic plasticity following MD. Two-week-old mice were monocularly deprived for a period of 5-7 d and miniature EPSCs (mEPSCs) were obtained from cells located in dLGN regions receiving input from the deprived or nondeprived eye. We found that MD promotes increases in the frequency and amplitude of mEPSCs and were restricted to the monocular segment contralateral to the deprived eye. These changes were accompanied by an increase in the probability of glutamate release at corticothalamic terminals that arise from the deprived visual cortex. Our findings indicate that homeostatic synaptic regulation from MD extends beyond cortical circuitry and shed light on how the brain modulates and integrates activity in the face of altered sensory experience.

Morphologically distinct classes of relay cells exhibit regional preferences in the dorsal lateral geniculate nucleus of the mouse.

A fundamental feature of the mammalian visual system is the presence of separate channels that work in parallel to efficiently extract and analyze specific elements of a visual scene. Despite the extensive use of the mouse as a model system, it is not clear whether such parallel organization extends beyond the retina to subcortical structures, such as the dorsal lateral geniculate (dLGN) of thalamus. To begin to address this, we examined the morphology of biocytin-filled relay cells recorded in dLGN of mice. Based on a quantitative assessment of their dendritic architecture, we found that even at early postnatal ages relay cells could be readily classified as X-like (biconical), Y-like (symmetrical), or W-like (hemispheric) and that each cell type was regionally specified in dLGN. X-like cells were confined primarily to the monocular ventral region of dLGN. Y-like cells occupied a central core that also contained ipsilateral eye projections, whereas W-like cells were found along the perimeter of dLGN. Similar to cat, Y-like cells were more prevalent than X- and W-like cells, and X-like cells tended to be smaller than other cell types. However, the dendritic fields of X- and W-like cells did not exhibit an orientation bias with respect to optic tract or boundaries of dLGN. Although we found clear morphological differences among relay cells, an analysis of their electrophysiological properties did not reveal any additional distinguishing characteristics. Overall, these data coupled with recent observations in the retina suggest that the mouse has many of the hallmark features of a system-wide parallel organization.

Modulation of CREB in the dorsal lateral geniculate nucleus of dark-reared mice.

The cAMP-response element-binding protein (CREB) plays an important role in visual cortical plasticity that follows the disruption of sensory activity, as induced by dark rearing (DR). Recent findings indicate that the dorsal lateral geniculate nucleus (dLGN) of thalamus is also sensitive to altered sensory activity. DR disrupts retinogeniculate synaptic strength and pruning in mice, but only when DR starts one week after eye opening (delayed DR, DDR) and not after chronic DR (CDR) from birth. While DR upregulates CREB in visual cortex, whether it also modulates this pathway in dLGN remains unknown. Here we investigate the role of CREB in the dLGN of mice that were CDR or DDR using western blot and immunofluorescence. Similar to findings in visual cortex, CREB is upregulated in dLGN after CDR and DDR. These findings are consistent with the proposal that DR up-regulates the CREB pathway in response to decreased visual drive.

High-sugar/high-fat diet modulates the effects of chronic stress in cariocas high- and low-conditioned freezing rats.

Stress and eating disorders are closely related and are a topic of major concern due to their burden on human health. Engaging in unhealthy eating habits may come as a result of stress, and it often serves to alleviate the symptoms of anxiety or as a distraction from the stressor itself or self-awareness. However, it can also lead to negative feelings of a person's body figure, guilty, or shame. As diverse as these consequences are in humans, so are the effects of the combined administration of stress and hypercaloric food in animals' models. In this study, we assessed the influence of individual innate behavioral predisposition on the effects of chronic unpredictable mild stress and the dietary supplementation with high-sugar/high-fat food. These conditions were applied to male Carioca low- and high-conditioned freezing (CLF and CHF) rats for 21 days. Behavioral results show that the hypercaloric supplement had a protective effect over the alterations caused by the stress. Notably, it was more strongly observed in CHF rather than CLF animals. As the chronic stress led to an impaired behavior in the contextual fear conditioning and the forced swimming tests in the CLF line, animals fed with the HSHF pellet scored responses similar to their untreated control. On CHF rats, these effects also were seen to a broader extent on the open field test, where the locomotor behavior was also increased. No major effects of the diet were seen in the unstressed groups. Overall, our results show that the influences of both chronic stress and hypercaloric feeding depend on innate differences in fear response traits of male Carioca rats.

Overexpression of serum response factor restores ocular dominance plasticity in a model of fetal alcohol spectrum disorders.

Neuronal plasticity deficits underlie many of the neurobehavioral problems seen in fetal alcohol spectrum disorders (FASD). Recently, we showed that third trimester alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. For instance, a few days of monocular deprivation results in a robust reduction of cortical regions responsive to the deprived eye in normal animals, but not in ferrets exposed early to alcohol. This plasticity deficit can be reversed if alcohol-exposed animals are treated with a phosphodiesterase type 1 (PDE1) inhibitor during the period of monocular deprivation. PDE1 inhibition can increase cAMP and cGMP levels, activating transcription factors such as the cAMP response element binding protein (CREB) and the serum response factor (SRF). SRF is important for many plasticity processes such as LTP, LTD, spine motility, and axonal pathfinding. Here we attempt to rescue OD plasticity in alcohol-treated ferrets using a Sindbis viral vector to express a constitutively active form of SRF during the period of monocular deprivation. Using optical imaging of intrinsic signals and single-unit recordings, we observed that overexpression of a constitutively active form of SRF, but neither its dominant-negative nor GFP, restored OD plasticity in alcohol-treated animals. Surprisingly, this restoration was observed throughout the extent of the primary visual cortex and most cells infected by the virus were positive for GFAP rather than NeuN. This finding suggests that overexpression of SRF in astrocytes may reduce the deficits in neuronal plasticity seen in models of FASD.

Forced swimming stress increases natatory activity of lead-exposed mice.

Recent evidence points to the relationship between lead toxicity and the function of the hypothalamic-pituitary-adrenal axis, which suggests that lead exposure could influence how an individual cope with stress. Here we test this hypothesis by investigating the behavioral effects of lead exposure in mice during the forced swimming test (FST), a parading in which animals are exposed to a stressful situation and environment. Swiss mice received either 180 ppm or 540 ppm of lead acetate (Pb) in their ad-lib water supply for 60-90 days, starting at postnatal day 30. Control (Ctrl) mice drank tap water. At the end of the exposure period, mice were submitted to a 5-min session of FST or to an open-field session of the same duration. Data from naïve animals showed that corticosterone levels were higher for animals tested in the FST compared to animals tested in the open-field. Blood-lead levels (BLL) in Pb-exposed mice ranged from 14.3 to 106.9 µg/dL. No differences were observed in spontaneous locomotion between Ctrl and Pb-exposed groups in the open-field. However, in the FST, Pb-treated mice displayed higher swimming activity than Ctrl ones and this effect was observed even for animals with BLL higher than 20 µg/dL. Furthermore, significant differences in brain glutathione levels, used as an indicator of led toxicity, were only observed for BLL higher than 40 µg/dL. Overall, these findings suggest that swimming activity in the FST is a good indicator of lead toxicity and confirm our prediction that lead toxicity influences behavioral responses associated to stress.

Activation of NMDA receptors is necessary for the recovery of cortical binocularity.

Classic experiments have indicated that monocular deprivation (MD) for a few days during a critical period of development results in a decrease in the strength of connections mediating responses to the deprived eye, leading to a dramatic breakdown of cortical neuron binocularity. Despite the substantial functional change in the visual cortex, recovery from the effects of MD can be obtained if binocular vision is promptly restored. While great efforts have been made to elucidate the mechanisms regulating loss of deprived eye function, the mechanisms that underlie the recovery of cortical binocularity are poorly understood. Here, we examined whether activation of the N-methyl-d-aspartate receptor (NMDAR) is required for the recovery of cortical binocularity by pharmacologically blocking the NMDAR using d,l-2-amino-5-phosphonopentanoic (APV). Ferrets (n = 10) were monocularly deprived for 6 days, and osmotic minipumps, filled with APV (5.6 mg/ml) or saline, were surgically implanted into the primary visual cortex. One day after surgery, the deprived eye was reopened, and the animals were allowed 24 h of binocular vision. Extracellular recordings showed that intracortical infusion of the NMDAR antagonist, APV, prevented recovery of cortical binocularity while preserving neuronal responsiveness. These findings provide an important new insight for a specific role of NMDARs in the recovery of cortical binocularity from the effects of MD.

Phosphodiesterase type 4 inhibition does not restore ocular dominance plasticity in a ferret model of fetal alcohol spectrum disorders.

BACKGROUND: There is growing evidence that deficits in neuronal plasticity account for some of the neurological problems observed in fetal alcohol spectrum disorders (FASD). Recently, we showed that early alcohol exposure results in a permanent impairment in visual cortex ocular dominance (OD) plasticity in a ferret model of FASD. This disruption can be reversed, however, by treating animals with a Phosphodiesterase (PDE) type 1 inhibitor long after the period of alcohol exposure. AIM: Because the mammalian brain presents different types of PDE isoforms we tested here whether inhibition of PDE type 4 also ameliorates the effects of alcohol on OD plasticity. MATERIAL AND METHODS: Ferrets received 3.5 g/Kg alcohol i.p. (25% in saline) or saline as control every other day between postnatal day (P) 10 to P30, which is roughly equivalent to the third trimester equivalent of human gestation. Following a prolonged alcohol-free period (10 to 15 days), ferrets had the lid of the right eye sutured closed for 4 days and were examined for ocular dominance changes at the end of the period of deprivation. RESULTS: Using in vivo electrophysiology we show that inhibition of PDE4 by rolipram does not restore OD plasticity in alcohol-treated ferrets. CONCLUSION: This result suggests that contrary to PDE1, PDE4 inhibition does not play a role in the restoration of OD plasticity in the ferret model of FASD.