Subimal Datta

The homeostatic regulation of REM sleep: A role for localized expression of brain-derived neurotrophic factor in the brainstem

Homeostatic regulation of REM sleep plays a key role in neural plasticity and deficits in this process are implicated in the development of many neuropsychiatric disorders. Little is known, however, about the molecular mechanisms that underlie this homeostatic regulation process. This study examined the hypothesis that, during selective REM sleep deprivation (RSD), increased brain-derived neurotrophic factor (BDNF) expression in REM sleep regulating areas is critical for the development of homeostatic drive for REM sleep, as measured by an increase in the number of REM sleep transitions. Rats were assigned to RSD, non-sleep deprived (BSL), or total sleep deprivation (TSD) groups. Physiological recordings were obtained from cortical, hippocampal, and pontine EEG electrodes over a 6h period, in which sleep deprivation occurred during the first 3h. In the RSD, but not the other conditions, homeostatic drive for REM sleep increased progressively. BDNF protein expression was significantly greater in the pedunculopontine tegmentum (PPT) and subcoeruleus nucleus (SubCD) in the RSD as compared to the TSD and BSL groups, areas that regulate REM sleep, but not in the medial preoptic area, which regulates non-REM sleep. There was a significant positive correlation between RSD-induced increases in number of REM sleep episodes and increased BDNF expression in the PPT and SubCD. These increases positively correlated with levels of homeostatic drive for REM sleep. These results, for the first time, suggest that selective RSD-induced increased expression of BDNF in the PPT and SubCD are determinant factors in the development of the homeostatic drive for REM sleep.

Activation of brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling in the pedunculopontine tegmental nucleus: a novel mechanism for the homeostatic regulation of rapid eye movement sleep

Rapid eye movement (REM) sleep dysregulation is a symptom of many neuropsychiatric disorders, yet the mechanisms of REM sleep homeostatic regulation are not fully understood. We have shown that, after REM sleep deprivation, the pedunculopontine tegmental nucleus (PPT) plays a critical role in the generation of recovery REM sleep. In this study, we used multidisciplinary techniques to show a causal relationship between brain‐derived neurotrophic factor (BDNF)‐tropomyosin receptor kinase B (TrkB) signaling in the PPT and the development of REM sleep homeostatic drive. Rats were randomly assigned to conditions of unrestricted sleep or selective REM sleep deprivation (RSD) with PPT microinjections of vehicle control or a dose of a TrkB receptor inhibitor (2, 3, or 4 nmol K252a or 4 nmol ANA‐12). On experimental days, rats received PPT microinjections and their sleep‐wake physiological signals were recorded for 3 or 6 h, during which selective RSD was performed in the first 3 h. At the end of all 3 h recordings, rats were killed and the PPT was dissected out for BDNF quantification. Our results show that K252a and ANA‐12 dose‐dependently reduced the homeostatic responses to selective RSD. Specifically, TrkB receptor inhibition reduced REM sleep homeostatic drive and limited REM sleep rebound. There was also a dose‐dependent suppression of PPT BDNF up‐regulation, and regression analysis revealed a significant positive relationship between REM sleep homeostatic drive and the level of PPT BDNF expression. These data provide the first direct evidence that activation of BDNF‐TrkB signaling in the PPT is a critical step for the development of REM sleep homeostatic drive.

Beyond Emotional and Spatial Processes: Cognitive Dysfunction in a Depressive Phenotype Produced by Long Photoperiod Exposure

Cognitive dysfunction in depression has recently been given more attention and legitimacy as a core symptom of the disorder. However, animal investigations of depression-related cognitive deficits have generally focused on emotional or spatial memory processing. Additionally, the relationship between the cognitive and affective disturbances that are present in depression remains obscure. Interestingly, sleep disruption is one aspect of depression that can be related both to cognition and affect, and may serve as a link between the two. Previous studies have correlated sleep disruption with negative mood and impaired cognition. The present study investigated whether a long photoperiod-induced depressive phenotype showed cognitive deficits, as measured by novel object recognition, and displayed a cognitive vulnerability to an acute period of total sleep deprivation. Adult male Wistar rats were subjected to a long photoperiod (21L:3D) or a normal photoperiod (12L:12D) condition. Our results indicate that our long photoperiod exposed animals showed behaviors in the forced swim test consistent with a depressive phenotype, and showed significant deficits in novel object recognition. Three hours of total sleep deprivation, however, did not significantly change novel object recognition in either group, but the trends suggest that the long photoperiod and normal photoperiod groups had different cognitive responses to total sleep deprivation. Collectively, these results underline the extent of cognitive dysfunction present in depression, and suggest that altered sleep plays a role in generating both the affective and cognitive symptoms of depression.

Sleep-Dependent Oscillatory Synchronization: A Role in Fear Memory Consolidation

Sleep plays an important role in memory consolidation through the facilitation of neuronal plasticity; however, how sleep accomplishes this remains to be completely understood. It has previously been demonstrated that neural oscillations are an intrinsic mechanism by which the brain precisely controls neural ensembles. Inter-regional synchronization of these oscillations is also known to facilitate long-range communication and long-term potentiation (LTP). In the present study, we investigated how the characteristic rhythms found in local field potentials (LFPs) during non-REM and REM sleep play a role in emotional memory consolidation. Chronically implanted bipolar electrodes in the lateral amygdala (LA), dorsal and ventral hippocampus (DH, VH), and the infra-limbic (IL), and pre-limbic (PL) prefrontal cortex were used to record LFPs across sleep-wake activity following each day of a Pavlovian cued fear conditioning paradigm. This resulted in three principle findings: (1) theta rhythms during REM sleep are highly synchronized between regions; (2) the extent of inter-regional synchronization during REM and non-REM sleep is altered by FC and EX; (3) the mean phase difference of synchronization between the LA and VH during REM sleep predicts changes in freezing after cued fear extinction. These results both oppose a currently proposed model of sleep-dependent memory consolidation and provide a novel finding which suggests that the role of REM sleep theta rhythms in memory consolidation may rely more on the relative phase-shift between neural oscillations, rather than the extent of phase synchronization.

BNDF heterozygosity is associated with memory deficits and alterations in cortical and hippocampal EEG power

&NA; Brain derived neurotrophic factor (BDNF) plays a pivotal role in structural plasticity, learning, and memory. Electroencephalogram (EEG) spectral power in the cortex and hippocampus has also been correlated with learning and memory. In this study, we investigated the effect of globally reduced BDNF levels on learning behavior and EEG power via BDNF heterozygous (KO) rats. We employed several behavioral tests that are thought to depend on cortical and hippocampal plasticity to varying degrees: novel object recognition, a test that is reliant on a variety of cognitive systems; contextual fear, which is highly hippocampal‐dependent; and cued fear, which has been shown to be amygdala‐dependent. We also examined the effects of BDNF reduction on cortical and hippocampal EEG spectral power via chronically implanted electrodes in the motor cortex and dorsal hippocampus. We found that BDNF KO rats were impaired in novelty recognition and fear memory retention, while hippocampal EEG power was decreased in slow waves and increased in fast waves. Interestingly, our results, for the first time, show sexual dimorphism in each of our tests. These results support the hypothesis that BDNF drives both cognitive plasticity and coordinates EEG activity patterns, potentially serving as a link between the two. HighlightsBDNF heterozygous rats display sex‐specific deficits in novel object recognition.BDNF heterozygous rats have impaired fear acquisition.EEG power in BDNF heterozygous rats is decreased in delta and increased in beta and gamma.BDNF heterozygous rats displayed sex‐specific differences in electrophysiological and behavioral tests.

Changes in Brain-Derived Neurotrophic Factor Expression Influence Sleep–Wake Activity and Homeostatic Regulation of Rapid Eye Movement Sleep

Abstract Study Objectives Brain-derived neurotrophic factor (BDNF) expression and homeostatic regulation of rapid eye movement (REM) sleep are critical for neurogenesis and behavioral plasticity. Accumulating clinical and experimental evidence suggests that decreased BDNF expression is causally linked with the development of REM sleep-associated neuropsychiatric disorders. Therefore, we hypothesize that BDNF plays a role in sleep–wake (S–W) activity and homeostatic regulation of REM sleep. Methods Male and female wild-type (WT; BDNF +/+) and heterozygous BDNF (KD; BDNF +/−) rats were chronically implanted with S–W recording electrodes to quantify baseline S–W activity and REM sleep homeostatic regulatory processes during the light phase. Results Molecular analyses revealed that KD BDNF rats had a 50% decrease in BDNF protein levels. During baseline S–W activity, KD rats exhibited fewer REM sleep episodes that were shorter in duration and took longer to initiate. Also, the baseline S–W activity did not reveal any sex difference. During the 3-hour selective REM sleep deprivation, KD rats failed to exhibit a homeostatic drive for REM sleep and did not exhibit rebound REM sleep during the recovery S–W period. Conclusion Interestingly, both genotypes did not reveal any sex difference in the quality and/or quantity of REM sleep. Collectively, these results, for the first time, unequivocally demonstrate that an intact BDNF system in both sexes is a critical modulator for baseline and homeostatic regulation of REM sleep. This study further suggests that heterozygous BDNF knockdown rats are a useful animal model for the study of the cellular and molecular mechanisms of sleep regulation and cognitive functions of sleep.

Cellular and Molecular Mechanisms of REM Sleep Homeostatic Drive: A Plausible Component for Behavioral Plasticity

Homeostatic regulation of REM sleep drive, as measured by an increase in the number of REM sleep transitions, plays a key role in neuronal and behavioral plasticity (i.e., learning and memory). Deficits in REM sleep homeostatic drive (RSHD) are implicated in the development of many neuropsychiatric disorders. Yet, the cellular and molecular mechanisms underlying this RSHD remain to be incomplete. To further our understanding of this mechanism, the current study was performed on freely moving rats to test a hypothesis that a positive interaction between extracellular-signal-regulated kinase 1 and 2 (ERK1/2) activity and brain-derived neurotrophic factor (BDNF) signaling in the pedunculopontine tegmentum (PPT) is a causal factor for the development of RSHD. Behavioral results of this study demonstrated that a short period (<90 min) of selective REM sleep restriction (RSR) exhibited a strong RSHD. Molecular analyses revealed that this increased RSHD increased phosphorylation and activation of ERK1/2 and BDNF expression in the PPT. Additionally, pharmacological results demonstrated that the application of the ERK1/2 activation inhibitor U0126 into the PPT prevented RSHD and suppressed BDNF expression in the PPT. These results, for the first time, suggest that the positive interaction between ERK1/2 and BDNF in the PPT is a casual factor for the development of RSHD. These findings provide a novel direction in understanding how RSHD-associated specific molecular changes can facilitate neuronal plasticity and memory processing.

Feel Better But Exercise Less: An Examination of Exercise Enjoyment, Personality and Physical Activity in Young Adults

The purpose of the present study was to examine aspects of personality and exercise enjoyment on physical activity levels in young adults. Fifty-three undergraduate students (22 males and 31 females) participated in this study. Participants were asked to complete surveys assessing exercise enjoyment, personality, and physical activity level. Participants were then asked to ride a bike for 30-minutes at a moderate intensity (at 65% maximal heart rate) to assess mood. Statistical analyses revealed that physical activity was strongly correlated with enjoyment of exercise. Highly physically active participants self-reported significantly less neuroticism and greater extraversion than less active participants. After the exercise bout, there was a significant improvement in mood, with more neurotic individuals reporting the greatest improvements. The findings observed in this study emphasize the need for mental health and fitness practitioners to develop exercise programs that address individual needs and encourage the enjoyment of exercise in order to promote well-being among young adults.

A sympathetic nervous system evaluation of obesity stigma

The portrayal of obesity in the media is often one of negativity. Consequently, it may generate an increase in stigma. Obesity stigma, a form of social discrimination, is responsible for many of the negative psychological and physiological effects on individual wellness. These effects not only impact individual health, but also affect the economy, and ultimately, societal wellness. In an attempt to examine the influence of the media on obesity stigma, this study tested the hypothesis that positive priming would lead to a reduction in obesity stigma. To further our understanding of this relationship, we: 1) examined the role of priming on physiological measures (e.g. salivary alpha amylase and skin conductance) in 70 college students by introducing positive and negative media images of individuals with obesity, and 2) assessed psychological measures (e.g. perceived stress, need to belong, and self-esteem, and Body Mass Index). After the priming manipulation, participants read a vignette depicting the discrimination of an individual with obesity and answered subsequent questions assessing participants’ attributional blame of obesity. Results of this study revealed that priming affects physiological responding to obesity stigmatization. In conclusion, these findings suggest that incorporating positive media images of individuals with obesity may be an effective tool for reducing stigma and the various physiological consequences associated with it, which in turn, can enhance societal health and wellness.

Wellness among African-American and Caucasian students attending a predominantly White institution

The wellness movement is growing on college campuses; however, the examination of race is lacking. We examined aspects of physical and emotional well-being as a function of race in 197 college students at a predominantly White institution. Results revealed racial differences on diet, F(1, 196) = 7.537, p = 0.007 and resilient coping, F(1, 196) = 8.614, p = 0.004. Furthermore, regression analyses revealed that the association between stress and coping was moderated by race (F(1, 196) = 8.196, p = 0.005), demonstrating that Whites and Blacks experience and cope with stressors in differing ways. Findings of this study suggest that race is an influential factor of wellness and subsequent well-being in college students.