Cytoarchitectural characteristics associated with cognitive flexibility in raccoons.

With rates of psychiatric illnesses such as depression continuing to rise, additional preclinical models are needed to facilitate translational neuroscience research. In the current study, the raccoon (Procyon lotor) was investigated due to its similarities with primate brains, including comparable proportional neuronal densities, cortical magnification of the forepaw area, and cortical gyrification. Specifically, we report on the cytoarchitectural characteristics of raccoons profiled as high, intermediate, or low solvers in a multiaccess problem-solving task. Isotropic fractionation indicated that high-solvers had significantly more cells in the hippocampus (HC) than the other solving groups; further, a nonsignificant trend suggested that this increase in cell profile density was due to increased nonneuronal (e.g., glial) cells. Group differences were not observed in the cellular density of the somatosensory cortex. Thionin-based staining confirmed the presence of von Economo neurons (VENs) in the frontoinsular cortex, although no impact of solving ability on VEN cell profile density levels was observed. Elongated fusiform cells were quantified in the HC dentate gyrus where high-solvers were observed to have higher levels of this cell type than the other solving groups. In sum, the current findings suggest that varying cytoarchitectural phenotypes contribute to cognitive flexibility. Additional research is necessary to determine the translational value of cytoarchitectural distribution patterns on adaptive behavioral outcomes associated with cognitive performance and mental health.

Natural-enriched environments lead to enhanced environmental engagement and altered neurobiological resilience.

The mammalian brain has evolved in close synchrony with the natural environment; consequently, trends toward disengagement from natural environments in today's industrialized societies may compromise adaptive neural responses and lead to psychiatric illness. Investigations of rodents housed in enriched environments indicate enhanced neurobiological complexity; yet, the origin of these stimuli, natural vs. manufactured, has not been sufficiently explored. In the current study, groups of rats were exposed to one of three environments: (1) a standard environment with only food and water, (2) an artificial-enriched environment with manufactured stimuli and (3) a natural-enriched environment with natural stimuli. Results indicated that, during the dark phase, natural-enriched animals exhibited longer durations interacting with objects than the artificial-enriched group; further, the natural-enriched group engaged in more social behavior than the other two groups. Both enriched groups exhibited less anxiety in response to a novel object but the natural-enriched rats exhibited less anxiety-typical behavior in response to a predator odor than the other groups. Less fos activation in the amygdala was observed in both enriched groups following a water escape task whereas an increase in fos activation in the nucleus accumbens was observed in the natural-enriched animals. Thus, the current findings indicate the potential importance of exposure to complex environments, especially natural-like habitats, in the maintenance of emotional health, perhaps providing a buffer against the emergence of anxiogenic responses.

Contingency-based emotional resilience: effort-based reward training and flexible coping lead to adaptive responses to uncertainty in male rats.

Emotional resilience enhances an animal's ability to maintain physiological allostasis and adaptive responses in the midst of challenges ranging from cognitive uncertainty to chronic stress. In the current study, neurobiological factors related to strategic responses to uncertainty produced by prediction errors were investigated by initially profiling male rats as passive, active or flexible copers (n = 12 each group) and assigning to either a contingency-trained or non-contingency trained group. Animals were subsequently trained in a spatial learning task so that problem solving strategies in the final probe task, as well-various biomarkers of brain activation and plasticity in brain areas associated with cognition and emotional regulation, could be assessed. Additionally, fecal samples were collected to further determine markers of stress responsivity and emotional resilience. Results indicated that contingency-trained rats exhibited more adaptive responses in the probe trial (e.g., fewer interrupted grooming sequences and more targeted search strategies) than the noncontingent-trained rats; additionally, increased DHEA/CORT ratios were observed in the contingent-trained animals. Diminished activation of the habenula (i.e., fos-immunoreactivity) was correlated with resilience factors such as increased levels of DHEA metabolites during cognitive training. Of the three coping profiles, flexible copers exhibited enhanced neuroplasticity (i.e., increased dentate gyrus doublecortin-immunoreactivity) compared to the more consistently responding active and passive copers. Thus, in the current study, contingency training via effort-based reward (EBR) training, enhanced by a flexible coping style, provided neurobiological resilience and adaptive responses to prediction errors in the final probe trial. These findings have implications for psychiatric illnesses that are influenced by altered stress responses and decision-making abilities (e.g., depression).

Effort-Based Reward (EBR) training enhances neurobiological efficiency in a problem-solving task: insights for depression therapies.

Effort-Based Reward (EBR) training strengthens associations between effort and rewards, leading to increased persistence in an unsolvable task when compared to control animals. EBR training involves placing animals in a test apparatus in which they are trained to dig in mounds to retrieve froot loop rewards (contingent group); these animals are compared to control animals that are given the same number of rewards, regardless of expended effort (noncontingent group). In the current study, the effect of EBR training on performance in a spatial task (Dry Land Maze) was explored to determine cognitive resilience during behavioral testing. Additionally, animals received BrdU injections during training to assess the role of neurogenesis on subsequent behavioral performance. Following the probe test, animals were perfused so that fos-immunoreactive (ir) cells in the hippocampus and cortical areas could be assessed. Behavioral results indicated that contingent rats were approximately 50% more efficient in locating and interacting with the previous baited well during the probe test than noncontingent animals, recruiting approximately 20% less c-fos ir-cells in the insular cortex, retrosplenial cortex, and dentate gyrus. A multidimensional scaling analysis grouped noncontingent animals together in a quadrant characterized by high latencies to find the previous baited well and higher ir-cell activation in the aforementioned areas. Thus, our data support the hypothesis that the EBR training enhances both cognitive functioning and emotional regulation during challenging events. Considering the ongoing controversy about the efficacy of pharmacological interventions in treating depression, the EBR model provides a valuable alternative for the investigation of the neurobiology of mood disorders.

Reproductive experience facilitates recovery from kainic acid-induced neural insult in female Long-Evans rats.

The hormones of pregnancy and lactation (e.g., estrogen, progesterone, and oxytocin) have been shown to modulate learning, memory, and the restructuring of brain areas not traditionally associated with maternal behavior. Given the impact of reproductive experience on plasticity of brain areas such as the hippocampus, kainic acid (KA) was used in the current study to induce hippocampal-specific neurotoxic insult in adult multiparous and virgin Long-Evans rats. In Experiment I, Fluoro-Jade B, an indicant of degenerating cells, revealed significant neuronal damage in KA-treated hippocampi at 16 h post-injection in both maternal and virgin rats. In Experiment II, maternal and virgin rats were assessed in spatial and novel object preference tasks to determine the effects of KA on subsequent behavioral and cognitive responses. Twenty-four hours post injection, saline maternal animals exhibited superior memory in a spatial task. Further, maternal saline-injected rats were more similar to maternal KA-injected rats than both the virgin groups. Forty-eight hours following the KA or saline injection, compared to virgins, maternal animals demonstrated enhanced memory in the novel object memory test, regardless of type of injection. Further, neurobiological assessments in Experiment II indicated that virgin KA exposed rats had significantly more glial fibrillary acidic protein (GFAP)-immunoreactivity in the hippocampus, suggesting that they were in an earlier stage of neural recovery compared to maternal animals or, alternatively, may have exhibited more trauma than maternal animals. Together, these data suggest that the previously reported plasticity of the maternal brain may facilitate neural and behavioral recovery from neural insults.