Biomedical subjects

Subimal Datta

Publications and source records attributed to Subimal Datta.

17 recordsLinked to original sources

PubMed2006

Activation of pedunculopontine tegmental protein kinase A: a mechanism for rapid eye movement sleep generation in the freely moving rat.

Cells in the pedunculopontine tegmentum (PPT) play a key role in the generation of rapid eye movement (REM) sleep, but its intracellular signaling mechanisms remain unknown. In the current studies, the role of PPT intracellular protein kinase A (PKA) in the regulation of REM sleep was evaluated by comparing PKA subunit [catalytic (PKA(C alpha)) and regulatory (PKA(RI), PKA(RII alpha), and PKA(RII beta)) types] expression and activity in the PPT at normal, high, and low REM sleep conditions. To compare anatomical specificity, REM sleep-dependent expressions of these PKA subunits were also measured in the medial pontine reticular formation (mPRF), medial prefrontal cortex (mPFC), and anterior hypothalamus (AHTh). The results of these PKA subunit expression and activity studies demonstrated that the expression of PKA(C alpha) and PKA activity in the PPT increased and decreased during high and low REM sleep, respectively. Conversely, PKA(C alpha) expression and PKA activity decreased with high REM sleep in the mPRF. Expression of PKA(C alpha) also decreased in the mPFC and remained unchanged in the AHTh with high REM sleep. These subunit expression and PKA activity data reveal a positive relationship between REM sleep and increased PKA activity in the PPT. To test this molecular evidence, localized activation of cAMP-dependent PKA activity was blocked using a pharmacological technique. The results of this pharmacological study demonstrated that the localized inhibition of cAMP-dependent PKA activation in the PPT dose-dependently suppressed REM sleep. Together, these results provide the first evidence that the activation of the PPT intracellular PKA system is involved in the generation of REM sleep.

Animals↗

PubMed2005

Pontine-wave generator activation-dependent memory processing of avoidance learning involves the dorsal hippocampus in the rat.

The aim of this study was to test the hypothesis that the dorsal hippocampus plays a critical role in pontine-wave (P-wave) generator activation-dependent memory processing of two-way active avoidance (TWAA) learning. To achieve this objective, rats were given small bilateral lesions in the CA1, dentate gyrus (DG), or CA3 region of the dorsal hippocampus by microinjecting ibotenic acid. After recovery, lesioned and sham-lesioned rats were trained on a TWAA learning paradigm, allowed a 6-hr period of undisturbed sleep, and then were tested on the same TWAA paradigm. It was found that lesions in the CA3 region impaired retention of avoidance learning. Conversely, lesions in the CA1 and DG regions had no effect on TWAA learning retention. None of the groups showed any changes in the baseline sleep-wake cycle or in the acquisition of TWAA learning. All rats showed increased rapid eye movement (REM) sleep and increased REM sleep P-wave density during the subsequent 6-hr recording period. Impaired retention in the CA3 group occurred despite an increase in REM sleep and P-wave density, suggesting that during REM sleep, the P-wave generator interacts with the CA3 region of the dorsal hippocampus to aid in consolidation of TWAA learning. The results of the present study thus demonstrate that P-wave generator activation-dependent consolidation of memory requires an intact CA3 subfield of the dorsal hippocampus. The results also provide evidence that under mnemonic pressure, the dorsal hippocampus may not be involved directly in regulating the sleep-wake cycle.

Animals↗

PubMed2005

Novel role of brain stem pedunculopontine tegmental adenylyl cyclase in the regulation of spontaneous REM sleep in the freely moving rat.

Physiological activation of kainate receptors and GABA(B) receptors within the pedunculopontine tegmentum (PPT) is involved in regulation of rapid-eye-movement (REM) sleep. Because these two types of receptors may also directly and/or indirectly activate the intracellular cyclic adenosine monophosphate (cAMP) signaling pathway, we hypothesized that this signaling pathway may be involved in the PPT to regulate spontaneous REM sleep. To test this hypothesis, four different doses (0.25, 0.50, 0.75, and 1.0 nmol) of a specific adenylyl cyclase (AC) inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536), were microinjected bilaterally (100 nl/site) into the PPT, and the effects on REM sleep in freely moving chronically instrumented rats were quantified. By comparing alterations in the patterns of REM sleep after control injections of vehicle or one of the four different doses of SQ22536, the contributions made by each dose of SQ22536 to REM sleep were evaluated. The results demonstrated that the local microinjection of AC inhibitor SQ22536 into the PPT decreased the total amount of REM sleep for 3 h and increased slow-wave sleep (SWS) for 2 h in a dose-dependent manner. This reduction in REM sleep was due to increased latency and decreased frequency of REM sleep episodes. These results provide evidence that inhibition of AC within the PPT can successfully reduce REM sleep. These findings suggest that activation of the cAMP-signaling pathway within the cholinergic cell compartment of the PPT is an intracellular biochemical/molecular step for generating REM sleep in the freely moving rat.

Action Potentials↗

PubMed2005

Two-way active avoidance training-specific increases in phosphorylated cAMP response element-binding protein in the dorsal hippocampus, amygdala, and hypothalamus.

Previous studies have demonstrated that the activation of pontine-wave (P-wave) generating cells in the brainstem during post-training rapid eye movement (REM) sleep is critical for the consolidation of memory for two-way active avoidance (TWAA) learning in the rat. Here, using immunocytochemistry, we investigated the spatio-temporal distribution of CREB phosphorylation within different parts of the dorsal hippocampus, amygdala, and hypothalamus following a session of TWAA training in the rat. We show that the TWAA training trials increased phosphorylation of CREB (p-CREB) in the dorsal hippocampus, amygdala, amygdalo-hippocampal junction (AHi), and hypothalamus. However, the time intervals leading to training-induced p-CREB activity were different for different regions of the brain. In the dorsal hippocampus, p-CREB activity was maximal at 90 min and this activity disappeared by 180 min. In the AHi, activity of the p-CREB peaked by 180 min and disappeared by 360 min. In the amygdala, the p-CREB activity peaked at 180 min and still remained higher than the control at the 360 min interval. In the hypothalamus, at 90 min p-CREB activity was present only in the ventromedial hypothalamus; however, by 180 min this p-CREB activity was also present in the dorsal hypothalamus, perifornical area, and lateral hypothalamus. By 360 min, p-CREB activity disappeared from the hypothalamus. This TWAA training trials-induced spatiotemporal characteristic of CREB phosphorylation, for the first time, suggests that REM sleep P-wave generator activation-dependent memory processing involves different parts of the dorsal hippocampus, amygdala, and hypothalamus.

Amygdala↗

PubMed2005

Spatio-temporal activation of cyclic AMP response element-binding protein, activity-regulated cytoskeletal-associated protein and brain-derived nerve growth factor: a mechanism for pontine-wave generator activation-dependent two-way active-avoidance memory processing in the rat.

The present study explored possible physiological and molecular mechanisms of pontine-wave (P-wave) generator activation-dependent memory processing in the rat using a two-way active-avoidance learning paradigm. The results show that learning training increased rapid eye movement sleep and activated brainstem cells in the P-wave generator. During this period, there was a time-dependent increase in phosphorylation of cAMP response element-binding protein (CREB) in the dorsal hippocampus and amygdala and increased synthesis of activity-regulated cytoskeletal-associated protein (Arc) in the dorsal hippocampus, amygdala, frontal cortex and occipital cortex. Learning training also increased synthesis of brain-derived nerve growth factor (BDNF) in the occipital cortex, amygdala and dorsal hippocampus at different time intervals. During this time, the levels of nerve growth factor did not change. The results also show that the increase in rapid eye movement sleep P-wave density during the post-training 3-h recording session is positively correlated with the increased levels of phosphorylated CREB, BDNF and Arc in the dorsal hippocampus. These results suggest that memory processing of two-way active-avoidance learning may involve excitation of P-wave-generating cells in the brainstem and increased expression of phosphorylated CREB, Arc and BDNF in a time-dependent manner in the forebrain. These dynamic changes in cellular and molecular features provide considerable insight into the mechanisms of the P-wave generator activation-dependent memory consolidation process.

Amygdala↗

PubMed2004

Neurotoxic lesions of phasic pontine-wave generator cells impair retention of 2-way active avoidance memory.

STUDY OBJECTIVES: The aim of this study was to test the hypothesis that the activation of pontine (P)-wave generator is critical for the posttraining rapid eye movement (REM) sleep-dependent memory processing. DESIGN: Ibotenic acid was microinjected (0.5 microg in 0.05 microL) into the functionally identified P-wave generator in order to destroy the cell bodies and thus to study the effects of their destruction upon waking-sleep states, P-waves, and 2-way active avoidance memory. SETTING: Sleep research laboratory at Boston University School of Medicine. PARTICIPANTS: Adult male Sprague-Dawley rats (N = 27). INTERVENTIONS: Chronically implanted for recording polygraphic signs of sleep and bilateral guide tubes for the local microinjections into the P-wave generator. MEASUREMENTS AND RESULTS: The ibotenic acid produced a small spherical area (< or = 0.35 mm in diameter) of nerve cell loss centered on the P-wave generator. Bilateral lesioning of the P-wave generator decreased P-waves during REM sleep by > 95% without significantly changing the amounts of time spent in wake, slow-wave sleep, or REM sleep. In these P-wave generator-lesioned rats, acquisition of avoidance learning and posttraining wake-sleep changes were identical to those of the sham-lesioned rats. However, in the test trials, after 6 hours of undisturbed sleep-wake, P-wave generator-lesioned rats had no retention of avoidance memory. CONCLUSIONS: These findings, for the first time, provide direct evidence that P-wave-generating cells are critical for normal REM sleep-dependent memory processing. This evidence supports our hypothesis that the P-wave generator in the brainstem may act as an on switch to provide activating input to forebrain structures for sleep-dependent memory processing.

Animals↗

PubMed2004

Activation of phasic pontine-wave generator prevents rapid eye movement sleep deprivation-induced learning impairment in the rat: a mechanism for sleep-dependent plasticity.

Animal and human studies of sleep and learning have demonstrated that training on various tasks increases subsequent rapid eye movement (REM) sleep and phasic pontine-wave (P-wave) activity, followed by improvement in performance on the learned task. It is well documented that REM sleep deprivation after learning trials blocks the expected improvement in performance on subsequent retesting. Our aim was to test whether experimentally induced P-wave generator activation could eliminate the learning impairment produced by post-training REM sleep deprivation. Rats were trained on a two-way active avoidance-learning task. Immediately thereafter, two groups of those rats received a control vehicle (100 nl saline) microinjection and one group received a carbachol (50 ng in 100 nl saline) microinjection into the P-wave generator. The carbachol-injected group and one of the two control saline microinjected groups were selectively deprived of REM sleep during a 6 hr polygraphic recording session. All rats were then tested on the avoidance-learning task. The rats that received both the control saline injection and REM sleep deprivation showed learning deficits compared with the control saline-injected rats that were allowed to sleep normally. In contrast, the rats that received the carbachol microinjection and REM sleep deprivation demonstrated normal learning. These results demonstrate, for the first time, that carbachol-induced activation of the P-wave generator prevents the memory-impairing effects of post-training REM sleep deprivation. This evidence supports our hypothesis that the activation of the P-wave generator during REM sleep deprivation enhances a physiological process of memory, which occurs naturally during post-training REM sleep.

Animals↗

PubMed2004

Hippocampal theta rhythm is reduced by suppression of the H-current in septohippocampal GABAergic neurons.

Hippocampal learning and memory tasks are tightly coupled to the hippocampal theta rhythm, which is critically dependent on the medial septum/diagonal band of Broca (MSDB) although the underlying mechanisms remain unclear. The MSDB sends both cholinergic and GABAergic projections to the hippocampus. Here we show that: (i) septo-hippocampal GABAergic but not cholinergic neurons have a pacemaking current, the H-current, and that its selective blockade by ZD7288 reduces their spontaneous firing in rat brain slices; and (ii), local infusions of ZD7288 into the MSDB reduce exploration and sensory evoked hippocampal theta bursts in behaving rats. Thus, the H-current in septohippocampal GABAergic neurons modulates the hippocampal theta rhythm.

Animals↗

PubMed2003

Spontaneous REM sleep is modulated by the activation of the pedunculopontine tegmental GABAB receptors in the freely moving rat.

Considerable evidence suggests that the neurotransmitter gamma-aminobutyric acid (GABA)-ergic system and pedunculopontine tegmentum (PPT) in the brain stem are critically involved in the regulation of rapid-eye-movement (REM) sleep. GABA and its various receptors are normally present in the PPT cholinergic cell compartment. The aim of this study was to identify the role of GABA and its receptors in the regulation of REM sleep. To achieve this aim, specific receptors were activated differentially by local microinjection of selective GABA receptor agonists into the PPT while quantifying its effects on REM sleep in freely moving chronically instrumented rats (n = 21). The results demonstrated that when GABAB receptors were activated by local microinjection of a GABAB receptor selective agonist, baclofen, spontaneous REM sleep was suppressed in a dose-dependent manner. The optimum dose for REM sleep reduction was 1.5 nmol. In contrast, when GABAA and GABAC receptors were activated by microinjecting their receptor selective agonists, isoguvacine (ISGV) and cis-4-aminocrotonic acid (CACA), respectively, the total percentages of REM sleep did not change compared with the control values. In another eight freely moving rats, effects of baclofen application was tested on firing rates of REM-on cells (n = 12). Of those 12 neurons, 11 stopped firing immediately after application of baclofen [latency: 50 +/- 14 s (SD)] and remained almost silent for 130 +/- 12 min. Findings of the present study provide direct evidence that the PPT GABAB receptors and REM-on cells are involved in the regulation of REM sleep.

Action Potentials↗

PubMed2003

Regulation of rapid eye movement sleep in the freely moving rat: local microinjection of serotonin, norepinephrine, and adenosine into the brainstem.

STUDY OBJECTIVES: Considerable evidence suggests that rapid eye movement (REM) sleep is induced by glutamatergic activation of cholinergic cells within the pedunculopontine tegmentum (PPT). The aim of this study is to test a popular hypothesis that serotonin, norepinephrine, and adenosine act on PPT cells to regulate REM sleep. This study also tests an alternate hypothesis that serotonin may inhibit REM sleep signs by direct action on the individual REM sleep sign generators. DESIGN: Serotonin, norepinephrine, and adenosine were locally microinjected into the PPT and serotonin was microinjected into the pontine-wave (P-wave) generator (dorsal part of the locus subcoeruleus nucleus) while quantifying the effects on REM sleep and P-wave activity in freely moving rats. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Local microinjections of serotonin, norepinephrine, and adenosine into the PPT did not change REM sleep. Microinjection of serotonin into the P-wave generator suppressed P-wave activity but not REM sleep. CONCLUSIONS: The present findings provide direct evidence that serotonin, norepinephrine, and adenosine-induced REM sleep suppression in the behaving rat are not mediated by the PPT. The results also provide direct evidence, for the first time, that serotonin suppresses P-wave activity by acting directly on the P-wave generator. These results suggest that the serotonin-induced inhibition of REM sleep in the freely moving rat is probably not mediated through the mesopontine cholinergic cell compartment but, rather, through individual REM sleep sign generators.

Adenosine↗

PubMed2003

Effects of passive-avoidance training on sleep-wake state-specific activity in the basolateral and central nuclei of the amygdala.

This study examined the effects of intense emotional learning on the sleep-wake state-specific electroencephalographic (EEG) activities of the basolateral (BLA) and central (CeA) nuclei of the amygdala. Rats were trained on a passive-avoidance learning (PAL) protocol that was followed by 6 hr of undisturbed polygraphic recording and a PAL test. After PAL training, the total amount of REM sleep decreased: high-frequency EEG power decreased in the CeA during REM sleep and increased in the BLA during all sleep-wake stages. These results suggest that there is no homeostatic demand for REM sleep after intense emotional learning. However, the PAL-specific changes in the local EEG suggest that some form of memory processing may occur within the amygdala during REM sleep.

Amygdala↗

PubMed2003

Activation of the phasic pontine-wave generator enhances improvement of learning performance: a mechanism for sleep-dependent plasticity.

The aim of this study was to test the hypothesis that supplementary activation of the phasic pontine wave (P-wave) generator during rapid eye movement (REM) sleep enhances consolidation and integration of memories, resulting in improved learning. To test this hypothesis, two groups of rats were trained on a two-way active avoidance learning task in the morning. Immediately after training, one group of rats received a carbachol microinjection into the P-wave generator and the other group was microinjected with control saline into the same target area. After training trials and microinjections, rats were allowed a 6-h period of undisturbed sleep in the polygraphic recording chamber. At the end of 6 h of undisturbed sleep-wake recordings, rats were retested in a session of avoidance learning trials. After learning trials, the total percentage of time spent in REM sleep was significantly increased in both saline (15.36%)- and carbachol (17.70%)-microinjected rats. After learning trials, REM sleep P-wave density was significantly greater throughout the 6-h period of recordings in carbachol treated rats than in the saline treated rats. In the retrial session, the improvement in learning task performance was 22.75% higher in the carbachol-microinjected rats than in the saline-microinjected rats. These findings show that the consolidation and integration of memories create a homeostatic demand for P-waves. In addition, these findings provide experimental evidence, for the first time, that activation of the P-wave generator may enhance consolidation and integration of memories, resulting in improved performance on a recently learned task.

Animals↗

PubMed2002

Sleep-wake effects of meta-chlorophenyl piperazine and mianserin in the behaviorally depressed rat.

The present study examined the effects of meta-chlorophenyl piperazine (mCPP) and mianserin on the sleep-wake cycle of the clomipramine-induced behaviorally screened depressed rats. Six-hour polygraphic recordings were made between 06:00 and 12:00 h, after a single injection of either saline or mianserin or mCPP into the lateral cerebral ventricle (i.c.v.) of both the depressed (n=12) and control rats (n=12). The injection of mCPP in the depressed rats caused a significant reduction in the total duration and number of rapid eye movement (REM) sleep episodes while it increased the REM sleep onset latency compared to the control saline injections. The injection of mianserin in the depressed rats also caused a significant reduction in the total duration and number of REM sleep episodes without changing the REM sleep latency. These results demonstrate for the first time that the central administration of mCPP and mianserin could act as an antidepressant in the clomipramine-induced rat model of depression.

Animals↗

PubMed2002

Single cell activity patterns of pedunculopontine tegmentum neurons across the sleep-wake cycle in the freely moving rats.

Microinjections of the excitatory amino acid, L-glutamate into the cholinergic cell compartment of the pedunculopontine tegmentum (PPT) of the rat induces both wakefulness and/or rapid eye movement (REM) sleep depending on the glutamate dosage. However, no studies have systematically recorded the electrical activity of these cells in the freely moving rat across the sleep-wake cycle. In this study, we have recorded the spontaneous activity patterns of single PPT cells (n = 70) in the freely moving rat across the sleep-wake cycle. PPT neurons were classified into three groups based on patterns in their spontaneous activity. The first group of cells (12.86%) was more active during REM sleep than they were during wakefulness or slow-wave sleep (SWS). The second group of cells (60.0%) was more active during REM and wakefulness than during SWS. The firing rate of the third group of cells (27.14%) did not change as a function of behavioral state. This study also demonstrated that the level of activity within the cholinergic cell compartment of the PPT during SWS drops to 7.4% of that observed during wakefulness and that during REM sleep it changes to 65.5% of wakefulness levels. These findings indicate that in the freely moving rat, the discharging of PPT neurons correlates with wakefulness and REM sleep. Additionally, these neurons may be an integral part of the brainstem wakefulness and REM sleep-generating mechanisms in the rat.

Action Potentials↗

PubMed2002

Sleep-wake effects of yohimbine and atropine in rats with a clomipramine-based model of depression.

The present study examined the sleep-wake cycle effects of microinjections of yohimbine, an adrenergic antagonist, and atropine, a cholinergic antagonist, into the cerebral ventricle of clomipramine-induced depressed rats. Yohimbine microinjection caused a significant reduction in the total duration and the number of REM sleep episodes compared to control saline injections. Atropine microinjection caused a significant reduction in the total duration and the number of REM sleep episodes without changing the REM sleep latency compared to control saline microinjection. These results show for the first time that the REM sleep disturbances observed in clomipramine-treatment induced depressed rats can be attenuated by increasing and decreasing the brain noradrenergic and cholinergic activities, respectively.

Acetylcholine↗

PubMed2002

Clomipramine treatment in neonatal rats alters the brain acetylcholinesterase activity in adulthood.

The enzyme, acetylcholinesterase, activity of the brain was measured in control and clomipramine-induced behaviorally depressed rats. Compared with control rats, the soluble form of acetylcholinesterase activity of the depressed rats was 31.8% higher in the hippocampus and 26.0% lower in the frontal cortex. However, the activity of soluble form of this enzyme was not significantly different in the hypothalamus, septum, and brainstem. These results suggest for the first time that the altered cholinergic activity in the specific areas of the brain may be involved in the behavioral depression observed in the rat model of human endogenous depression.

Acetylcholinesterase↗

PubMed2002

Evidence that REM sleep is controlled by the activation of brain stem pedunculopontine tegmental kainate receptor.

Glutamate, the neurotransmitter, enhances rapid-eye-movement (REM) sleep when microinjected into the brain stem pedunculopontine tegmentum (PPT) of the cat and rat. Glutamate and its various receptors are normally present in the PPT cholinergic cell compartment. The aim of this study was to identify which specific receptor(s) in the cholinergic cell compartment of the PPT are involved in glutamate-induced-REM sleep. To identify these glutamate-induced REM-sleep-generating receptor(s) in the PPT cholinergic cell compartment, specific receptors were pharmacologically blocked differentially by localized pretreatment of specific glutamate receptor antagonists; glutamate was then microinjected into the PPT cholinergic cell compartment while quantifying the effects on REM sleep in freely moving chronically instrumented rats. The results demonstrate that when kainate receptors were blocked by pretreatment with a kainate-specific receptor antagonist, microinjection of glutamate was unable to induce REM sleep. Pharmacological blockade of specific N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors was unable to block glutamate-microinjection-induced-REM sleep. These findings suggest, for the first time, that the activation of kainate receptors within the cholinergic cell compartment of the PPT is an essential portion of the mechanism for the generation of glutamate-induced REM sleep in the rat.

Animals↗