Ventral subicular lesion impairs pro-social empathy-like behavior in adult Wistar rats.

The subiculum, an important structure of the hippocampal formation, regulates spatial information processing, social cognition, and affective behavior. Earlier we demonstrated deficits in sociability and social novelty as a measure of social cognition in ventral subicular lesioned (VSL) rats. The present study investigated empathy-like pro-social behavior and the associated affective states in VSL rats. The ability of free rats to release trapped cagemates was assessed using a modified door-opening empathy task.The rat pairs (free rat and the trapped cagemate) used were from the same group and tested for eight days to assess the pro-social behavior displayed by the free rats. The controlfree rats learned to open the door quickly to release the trapped cagemate and both the rats displayed social responses by emitting 'hedonic' calls (50-kHz ultrasonic vocalizations) while playing after the release. The VSLfree rats, however, were less exploratory, displayed apathy towards the trapped cagemate, demonstrated freezing behavior following door-opening and did not interact with the cagemate even after its release. These findings indicate deficits of social motivation and reinforcement learning associated with lesions in possibly both the rats. In addition, the VSL rat pairs elicited more 22-kHz 'alarm' calls and fewer 50-kHz 'hedonic' calls highlighting the lesion-induced alterations of contextual processing and threat perception abilities. In conclusion, VSL led to significant pro-social deficits implicating the role of ventral subiculum in social cognition and empathy. More studies are needed to substantiate whether the subiculum is implicated in social deficits associated with psychiatric conditions such as autism spectrum disorder.

Exposure to Short Photoperiod Regime Restores Spatial Cognition in Ventral Subicular Lesioned Rats: Potential Role of Hippocampal Plasticity, Glucocorticoid Receptors, and Neurogenesis.

Ambient light influences our mood, behavior, and cognition. Phototherapy has been considered as an effective non-pharmacological intervention strategy in the restoration of cognitive functions following central nervous system insults. However, the cellular and molecular underpinnings of phototherapy-mediated functional recovery are yet to be studied. The present study examines the effectiveness of short photoperiod regime (SPR; 6:18-h light:dark cycle) in restoring the cognitive functions in ventral subicular lesioned rats. Bilateral ventral subicular lesion (VSL) resulted in significant impairment of spatial navigational abilities when tested in the Morris water maze (MWM) task. Further, VSL resulted in reduced expression of glucocorticoid receptors (GRs) and activity-regulated cytoskeletal (Arc) protein and suppression of neurogenesis in the hippocampus. VSL also suppressed the magnitude of long-term potentiation (LTP) in the hippocampal Schaffer collateral-CA1 synapses. However, exposure to SPR for 21 days showed significant restoration of spatial performance in the MWM task as the ventral subicular lesioned rats could deploy higher cognitive allocentric navigational strategies to reach the hidden platform. Further, SPR resulted in enhanced expression of hippocampal GR and Arc protein and neurogenesis but not hippocampal LTP suggestive of appropriate need-based SPR intervention. In conclusion, the study demonstrates the effectiveness of SPR in establishing functional recovery as well as the possible molecular and cellular basis of cognitive recovery in a rat model of neurodegeneration. Such studies provide a framework in understanding the efficacy of non-pharmacological strategies in establishing functional recovery in neurodegenerative conditions.

Short photoperiod restores ventral subicular lesion-induced deficits in affective and socio-cognitive behavior in male Wistar rats.

Photoperiod (day-length) has enduring effects on an organism's physiological functions like metabolism and behavioral phenotypes including cognition and affect. Circadian rhythm manipulations are potentially effective non-pharmacological strategies in the management of central nervous system insults. In our previous study, we demonstrated the efficacy of short photoperiod regime (SPR; 06/18 hr light-dark cycle) in establishing functional recovery in ventral subicular lesion (VSL) rats. The present study further demonstrates the efficacy of SPR in mitigating anxiety and depression as well as facilitating socio-cognitive behavior in VSL rats. VSL elevated the basal plasma corticosterone levels, increased anxiety, anhedonia, and behavioral despair with decreased self-care. The VSL rats also exhibited a considerable degree of impaired social cognition, in terms of altered social preference and social novelty. Exposure to SPR for 21 days mitigated the anxiety- and depressive-like phenotypes as well as improved social cognition significantly. Thus, the study demonstrated the effectiveness of SPR strategy in reversing most of the behavioral deficits caused by VSL. SPR, perhaps, would have regulated the hypothalamo-pituitary-adrenal axis responsiveness as we observed a decrease in plasma corticosterone levels following SPR in VSL rats. The study implies the need for developing a task-dependent SPR strategy to achieve complete behavioral recovery as the functional demands of each behavior is distinct. In summary, the study highlights the efficacy of photoperiod manipulation as a novel, non-pharmacological approach in mitigating the affective and cognitive deficits associated with neuropsychiatric disorders such as bipolar disorder and Alzheimer's disease wherein circadian rhythm alterations are implicated.

Exposure to short photoperiod regime reduces ventral subicular lesion-induced anxiety-like behavior in Wistar rats.

Neurodegeneration of hippocampal structures is implicated in Alzheimer's disease (AD). Patients with AD exhibit 'sundown syndrome' featuring mood swings and anxiety. Although there are studies demonstrating circadian rhythm disruption associated with sundown phenomenon, the mechanisms underlying the emotional disturbances remain elusive. In the present study, we examined the relationship between subiculum (a key hippocampal output structure) and anxiety. Our study demonstrates that bilateral ventral subicular lesion (VSL) leads to anxiogenic behavior. In the elevated plus maze test, VSL rats made less number of entries into the open arms and spent significantly more time in the closed arms. Similarly, in the light-dark exploration test, VSL rats spent significantly more time in the dark chamber and made fewer entries into the light chamber. VSL also produced significant neurodegeneration in the paraventricular, suprachiasmatic and dorsomedial nuclei of the hypothalamus. Exposing VSL rats to a short photoperiod regime (SPR; 06/18h light-dark cycle) for 21days ameliorated the anxiety-like behavior. VSL rats on SPR also exhibited increased food consumption and higher core body temperature. Our study supports the hypothesis that the ventral subiculum regulates anxiety-like behavior and that SPR helps in the alleviation of such behavior. Even though the mechanisms underlying anxiolytic effects of light-dark cycle manipulation are yet to be elucidated, such non-pharmacological strategies can help to mitigate anxiety-like behavior. A proper understanding of the effectiveness of photoperiod manipulation will help in developing strategies in the management of emotional disturbances associated with affective and neurodegenerative disorders including AD.