Sleep and memory relationships in intact old and amnestic young rats

Age-related changes in sleep are observed in many species, including rats and humans. Old rats often exhibit less total and paradoxical sleep, shorter sleep bouts and more random sleep-wake periods across 24 hours, than young rats. This paper evaluates recent evidence that deterioration of selected sleep parameters, usually involving levels of paradoxical sleep or durations of sleep bouts, may be related to deterioration of memory in old rats. Similar findings are reviewed with respect to young animals with different forms of experimentally-induced amnesia. Furthermore, a drug that enhances memory in rats and old humans, glucose, also enhances paradoxical sleep in old rats. These data suggest the utility of sleep measures as neurobiological markers of memory dysfunction in old rats.     

Effect of paradoxical sleep deprivation and stress on passive avoidance behavior

Previous studies have shown that several types of stress can induce memory impairment. However, the memory effects of paradoxical sleep deprivation (PSD), a stressor in itself, are unclear. We therefore compared passive avoidance behavior of rats undergoing PSD and PSD stress yoked-control (PSC) using the "reversed flowerpot method." When rats were kept isolated on a PSC platform for 24 h immediately after criterion training, retention trials showed impaired aversive memory storage. When delayed for 24 h after criterion training, PSC stress did not disrupt retention performance. In rats subjected to PSD, either immediately or 24 h after criterion training, there was no disruption of aversive memory consolidation. These results suggest that, during stress, paradoxical sleep plays a role in erasing aversive memory traces, in line with the theory that we "dream in order to forget."     

Age-dependent cerebral metabolic effects of unilateral nucleus basalis magnocellularis ablation in rats

To investigate the age-dependent functional importance of cholinergic neocortical inputs, and to explore whether cortical cholinergic denervation in aged animals might better model the cerebral metabolic changes of Alzheimer's disease, the effects of unilateral ablation of the nucleus basalis magnocellularis (NBM) on cerebral glucose metabolism were studied in young and aged rats. Regional cerebral metabolic rates for glucose (rCMRglc) were determined, using the [14C]deoxyglucose method, in 48 brain regions of 3- and 24-month old Fischer-344 rats at 3, 7, 14 and 28 days after stereotaxic injection of ibotenate into the right NBM, and in sham-operated animals at 3 and 14 days later. For both ages the peak effect of unilateral NBM ablation occurred 3 days later: in young rats, rCMRglc was significantly reduced (compared to the contralateral side) in all 24 anterior cortical areas examined (mean decline 20%), whereas in aged animals, only 9 of 24 areas showed a significant decline in glucose utilization, and the magnitude of rCMRglc reduction (9%) was smaller. Near complete recovery of rCMRglc occurred by 7 days in young and old rats. We conclude that the basalocortical cholinergic projection plays a smaller role in neocortical function of aged rats, possibly because its tonic activity is reduced. Both young and aged rats undergo cortical metabolic normalization after unilateral NBM ablation; hence the NBM-lesioned aged rat is not a better model of the progressive decline in rCMRglc that occurs in Alzheimer's disease.     

Further characterizations of the nature of the behavioral and neurochemical effects of lesions to the nucleus basalis of Meynert in the rat

Converging lines of evidence indicate an important role for the basal forebrain cholinergic system in memory processes. The principal origin of the cholinergic projection to the neocortex appears to be the magnocellular neurons in the region of the nucleus basalis of Meynert (NbM). We examined the effects of bilateral lesions of the NbM on retention of shock avoidance training by stereotaxically injecting rats with 0.5 microliter of ibotenic acid (14 micrograms/microliter) into the NbM. Two weeks later rats were given passive avoidance training and tested for retention of the original avoidance habit 5 min, 30 min, or 24 hr later. Rats with lesions of the NbM showed significantly impaired shock avoidance performance compared to non-operated controls at both 30 min and 24 hr, but not at 5 min after training. Lesioned animals also showed a significant decrease in cortical choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities. No differences in muscarinic receptor binding or plasma cholinesterase activity was observed. The results demonstrate the usefulness of NbM lesions as a model for studying the role of the basal forebrain cholinergic system in memory processes.     

Neonatal 6-hydroxydopamine lesions of the frontal cortex in rats: persisting effects on locomotor activity, learning and nicotine self-administration

Dopaminergic innervation of the frontal cortex in adults is important for a variety of cognitive functions and behavioral control. However, the role of frontal cortical dopaminergic innervation for neurobehavioral development has received little attention. In the current study, rats were given dopaminergic lesions in the frontal cortex with local micro-infusions of 6-hydroxydopamine (6-OHDA) at 1 week of age. The long-term behavioral effects of neonatal frontal cortical 6-OHDA lesions were assessed in a series of tests of locomotor activity, spatial learning and memory, and i.v. nicotine self-administration. In addition, neurochemical indices were assessed with tissue homogenization and HPLC in the frontal cortex, striatum, and nucleus accumbens of neonatal and adult rats after neonatal 6-OHDA lesions. In neonatal rats, frontal 6-OHDA lesions as intended caused a significant reduction in frontal cortical dopamine without effects on frontal cortical 5-HT and norepinephrine. The frontal cortical dopamine depletion increased 5-HT and norepinephrine levels in the nucleus accumbens. Locomotor activity assessment during adulthood in the figure-8 maze showed that lesioned male rats were hyperactive relative to sham-lesioned males. Locomotor activity of female rats was not significantly affected by the neonatal frontal 6-OHDA lesion. Learning and memory in the radial-arm maze was also affected by neonatal frontal 6-OHDA lesions. There was a general trend toward impaired performance in early maze acquisition and a paradoxical improvement at the end of cognitive testing. Nicotine self-administration showed significant lesion x sex interactions. The sex difference in nicotine self-administration with females self-administering significantly more nicotine than males was reversed by neonatal 6-OHDA frontal cortical lesions. Neurochemical studies in adult rats showed that frontal cortical dopamine and DOPAC levels significantly correlated with nicotine self-administration in the 6-OHDA-lesioned animals but not in the controls. Frontal cortical 5-HT and 5HIAA showed inverse correlations with nicotine self-administration in the 6-OHDA-lesioned animals but not in the controls. These results show that interfering with normal dopamine innervation of the frontal cortex during early postnatal development has persisting behavioral effects, which are sex-specific.     

Selective immunolesions of CH4 cholinergic neurons do not disrupt spatial memory in rats

Adult male Long-Evans rats were subjected to bilateral lesions of the cholinergic neurons in the nucleus basalis magnocellularis (NBM) by injection of 0.2 or 0.4 microg 192-IgG-saporin in 0.4 microl phosphate-buffered saline. Control rats received an equivalent amount of phosphate-buffered saline. Starting 2 weeks after surgery, all rats were tested for locomotor activity in their home cage, beam-walking performance, T-maze alternation rates (working memory), reference and working memory performance in a water-maze task, and memory capabilities in the eight-arm radial maze task using uninterrupted and interrupted (delay of 2 min, 2 h and 6 h after four arms had been visited) testing procedures. Histochemical analysis showed a significant decrease of acetylcholinesterase (AChE)-positive reaction products (30-66%) in various cortical regions at the 0.2-microg dose. At the dose of 0.4 microg, there was an additional, although weak, damage to the hippocampus (17-30%) and the cingulate cortex (34%). The behavioral results showed only minor impairments in spatial memory tasks, and only during initial phases of the tests (reference memory in the water maze, working memory in the radial maze). The behavioral effects of the dramatic cholinergic lesions do not support the idea of a substantial implication of cholinergic projections from the NBM to the cortex in the memory processes assessed in this study, but they remain congruent with an involvement of these projections in attentional functions.     

Lesions of the nucleus basalis magnocellularis in the rat: morphological, biochemical and behavioral reparative effect of nerve growth factor and ganglioside GM1

Three- and fifteen-month old rats with a unilateral ibotenic acid lesion of the nucleus basalis magnocellularis (NBM) were used. In 3-month old rats, 4 days after the lesion a 34 and 33% decrease in high affinity choline uptake (HACU) rate was found in the ipsilateral frontal and parietal cortices, respectively. Twenty-one days later the lesioned rats showed a loss in the NBM choline acetyltransferase (ChAT)-positive cells, a marked decrease in ipsilateral cortical ChAT activity and an impairment of the acquisition of a passive avoidance conditioned response. If the lesioned rats received nerve growth factor (NGF) (10 micrograms i.c.v.) twice a week or daily administration of ganglioside GM1 (GM1) (30 mg/kg i.p.), beginning immediately after surgery, the decreases in the HACU rate and ChAT activity were significantly smaller and the behavioral performance was normal. A potentiation by GM1 of NGF effects on the cholinergic neurons of the NBM occurred since no differences were detected between sham-operated rats and rats trated with NGF plus either the active (30 mg/kg) or inactive (10 mg/kg) dose of GM1. The loss in the number of NBM ChAT-positive neurons was reduced by GM1 or prevented by NGF administrations, indicating that the two drugs prevent the cholinergic deficit by protecting the cholinergic neurons of the NBM from ibotenic acid neurotoxicity. GM1 had no effect on ChAT activity decrease and behavioral impairment in 15-month old rats. The latter finding indicates an age-related loss of the ability of GM1 to enhance neurotrophic activity in the NBM.     

Sleep deficits in rats after NMDA receptor blockade.

N-Methyl-D-aspartate (NMDA) receptor blockade disrupts a variety of functions associated with neural plasticity, including acquisition of learned responses and long-term potentiation. Deficits in memory are significantly correlated with deficits in measures of paradoxical sleep in several amnesic populations. The present experiment therefore assessed whether NPC 12626, a competitive NMDA receptor antagonist, also disrupts sleep. NPC 12626 (1, 10, 50, and 100 mg/kg) or saline was administered to Sprague-Dawley rats 30 min prior to 3-h daytime recording periods. Paradoxical sleep was selectively impaired at all but the highest dose, which prevented all sleep during the recording period. Some deficits in nonparadoxical sleep first appeared at the 10 mg/kg dose but did not became prominent until the 50 mg/kg dose. The results thus show that NPC 12626 impairs sleep states in rats and demonstrate that paradoxical sleep is particularly susceptible to the effects of NMDA receptor blockade. These findings, along with previous evidence that NMDA antagonists impair waking measures of arousal, provide evidence that all sleep-wake states are impaired by NMDA receptor blockade. More generally, the results suggest that some brain mechanisms underlying sleep and memory may share common elements.     

The sequential hypothesis of sleep function. IV. A correlative analysis of sleep variables in learning and nonlearning rats.

Female adult rats were trained for a two-way active avoidance task (4 h), and allowed free sleep (3 h). Control rats (C) were left in their home cages during the acquisition period. Dural electrodes and an intraventricular cannula, implanted one week in advance, were used for EEG recording during the period of sleep and for the injection of [3H]thymidine at the beginning of the training session, respectively. Rats were killed at the end of the sleep period, and the DNA-specific activity was determined in the main brain regions and in liver. Correlations among sleep, behavioral and biochemical variables were assessed using Spearman's nonparametric method. In learning rats (L), the number of avoidances was negatively correlated with SS-W variables, and positively correlated with SS-PS variables (episodes of synchronized sleep followed by wakefulness or paradoxical sleep, respectively) and with PS variables. An inverse pattern of correlations was shown by the number of escapes or freezings. No correlations occurred in rats unable to achieve the learning criterion (NL). In L rats, the specific activity of brain DNA was negatively correlated with SS-W variables and positively correlated with SS-PS variables, while essentially no correlation concerned PS variables. On the other hand, in NL rats, comparable correlations were positive with SS-W variables and negative with SS-PS and PS variables. Few and weak correlations occurred in C rats. The data support a role of SS in brain information processing, as postulated by the sequential hypothesis on the function of sleep. In addition, they suggest that the elimination of nonadaptive memory traces may require several SS-W episodes and a terminal SS-PS episode. During PS episodes, adaptive memory traces cleared of nonadaptive components may be copied in more suitable brain sites.     

Physiologic effects of nucleus basalis magnocellularis stimulation on rat barrel cortex neurons

Cholinergic neurons in the nucleus basalis magnocellularis (NBM) project to the cerebral cortex and are thought to play an important role in learning and memory, and other cognitive functions. In the present study, we examined the effects of NBM stimulation on the response properties of individual cortical neurons in layer V of the rat somatosensory cortex. Seventy-three neurons were studied before and after a brief electrical stimulation of NBM. Transient changes in spontaneous activity were observed in 60% of the cells, and in most cases this background activity decreased. Recordings lasting more than 1 h stimulation were obtained from 56 cells. Because some NBM stimulation-induced effects lasted several hours, neurons were evaluated in two groups, NBM1 and NBM2. NBM1 neurons were those exposed to either the first NBM stimulation of the day or an NBM restimulation following a more than 5 h stimulation-free period. Neurons exposed to NBM restimulation following a stimulation free interval of less than 5 h were classified as NBM2. Sixty-nine percent of the 32 NBM1 neurons displayed marked decreases in spontaneous activity and/or increases in the response evoked by deflecting a contralateral facial vibrissa. NBM1 stimulation caused some units to respond to previously minimally effective whisker stimuli. Stimulation effects often lasted several hours. By contrast, long-lasting changes were observed in only 25% of the 24 NBM2 neurons, and the only consistent effect was on spontaneous, not stimulus-evoked, activity. Systemic injection of atropine blocked NBM stimulation-induced changes in spontaneous and stimulus-evoked activities. Control neurons, studied without NBM stimulation, failed to display consistent alterations in their response properties during the course of 1 h or more. Results demonstrate that NBM activation produces long-lasting, cholinergically mediated alterations in the response properties of somatosensory cortical neurons. Effects were complex, being influenced by factors such as the time interval between successive stimulations during an experiment. The complexity of these NBM mediated effects should be considered when designing therapies for neurodegenerative disorders characterized by loss of NBM neurons.     

Experimental sleep fragmentation impairs spatial reference but not working memory in Fischer/Brown Norway rats

Sleep fragmentation is a common symptom in sleep disorders and other medical complaints resulting in excessive daytime sleepiness. The present study seeks to explore the effects of sleep fragmentation on learning and memory in a spatial reference memory task and a spatial working memory (WM) task. Fischer/Brown Norway rats lived in custom treadmills designed to induce locomotor activity every 2 min throughout a 24-h period. Separate rats were either on a treadmill schedule that allowed for consolidated sleep or experienced no locomotor activation. Rats were tested in one of two water maze-based tests of learning and memory immediately following 24 h of sleep interruption. Rats tested in a spatial reference memory task (eight massed acquisition trials) with a 24-h follow-up probe trial to assess memory retention showed no differences in acquisition performance but were impaired on the 24 h retention of the platform location. In contrast, the performance of rats tested in a spatial WM task (delayed matching to position task) was not impaired. Therefore, sleep fragmentation prior to testing impairs the ability to retain spatial reference memories but does not impair spatial reference memory acquisition or spatial WM in Fischer-Norway rats.     

Individual differences in cognitive aging: implication of pregnenolone sulfate

In humans and animals, individual differences in aging of cognitive functions are classically reported. Some old individuals exhibit performances similar to those of young subjects while others are severely impaired. In senescent animals, we have previously demonstrated a significant correlation between the cognitive performance and the cerebral concentration of a neurosteroid, the pregnenolone sulfate (PREG-S).Neurotransmitter systems modulated by this neurosteroid were unknown until our recent report of an enhancement of acetylcholine (ACh) release in basolateral amygdala, cortex and hippocampus induced by intracerebroventricular (i.c.v.) or intracerebral administrations of PREG-S. Central ACh neurotransmission is known to be involved in the regulation of memory processes and is affected in normal aging and severely altered in human neurodegenerative pathologies like Alzheimer's disease.In the central nervous system, ACh neurotransmission is also involved in the modulation of sleep-wakefulness cycle, and particularly the paradoxical sleep (PS). Relationships between paradoxical sleep and memory are documented in the literature in old animals in which the spatial memory performance positively correlates with the basal amounts of paradoxical sleep. PREG-S infused at the level of ACh cell bodies (nucleus basalis magnocellularis, NBM, or pedunculopontine nucleus, PPT) increases paradoxical sleep in young animals.Finally, aging related cognitive dysfunctions, particularly those observed in Alzheimer's disease, have also been related to alterations of mechanisms underlying cerebral plasticity. Amongst these mechanisms, neurogenesis has been extensively studied recently. Our data demonstrate that PREG-S central infusions dramatically increase neurogenesis, this effect could be related to the negative modulator properties of this steroid at the GABA(A) receptor level.Taken together these data suggest that neurosteroids can influence cognitive processes, particularly in senescent subjects, through a modulation of ACh neurotransmission associated with paradoxical sleep modifications; furthermore, our recent data suggest a critical role for neurosteroids in the modulation of cerebral plasticity, mainly on hippocampal neurogenesis.     

Potential role of inducible nitric oxide synthase in the sleep-wake states occurrence in old rats

Extensive evidences now suggest that an association between inducible nitric oxide synthase and oxidative stress takes place during aging. Since the part played by inducible nitric oxide synthase in the sleep impairments associated with aging still remains unexplored, we compared its involvement in old rats (20-24 months) versus adult ones (3-5 months) using polygraphic, biochemical, voltammetric and immunohistochemical techniques. The experiments were conducted either in basal condition or after a systemic injection of selected inducible nitric oxide synthase inhibitors. We found that 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (10 mg/kg, i.p.) or aminoguanidine (400 mg/kg, i.p.) was capable to suppress rapid-eye-movement sleep and induce a delayed enhancement in slow-wave sleep in old rats. These effects did not occur in adult animals. Within the frontal cortex, the laterodorsal tegmentum and dorsal raphe nuclei, the basal inducible nitric oxide synthase activity was 85-200% higher in old rats than in adult ones. In contrast, the neuronal nitric oxide synthase activity did not vary in both groups. 2-Amino-5,6-dihydro-6-methyl-4H-1,3-thiazine administration significantly reduced inducible nitric oxide synthase activity (70-80% according to the brain areas) independently of age, but significantly decreased the cortical nitric oxide release in old rats. Finally, in frontal cortex and dorsal raphe immunohistochemical analysis showed inducible nitric oxide synthase-positive cells again only in old animals. These data support the idea that nitric oxide produced by inducible nitric oxide synthase plays a role in the triggering and maintenance of rapid-eye-movement sleep during aging.     

Changes in sleep-wakefulness pattern following bilateral olfactory bulbectomy in rats

Changes in emotionalities and 24-hr sleep-wakefulness pattern following olfactory bulbectomy were investigated in rats with chronic electrode implants. On the 3rd and 7th day after olfactory bulb (OB) ablations, no significant difference was found in slow wave sleep throughout the experimental period. On the other hand, paradoxical sleep (PS) was significantly decreased during the 24-hr and light period but not during the dark period. These changes, however, returned to the normal value on the 15th day after OB ablations. On the other hand, OB lesioned rats showed an increase in locomotor activity and hyperemotionality. The increase in locomotor activity was marked in the dark period. These behavioral changes were gradually produced following OB ablations and maintained for over 15 days. The time course of the reduction in PS following olfactory bulbectomy was not consistent with the time course of hyperemotionality and the increase of locomotor activity. These results suggest that a reduction in PS may play some role in the induction of hyperemotionality but not in its maintenance.     

Electrolytic and ibotenic acid lesions of the nucleus basalis magnocellularis interrupt long-term retention, but not acquisition of two-way active avoidance, in rats

Previous experiments on two-way active avoidance have shown conflicting results after nucleus basalis magnocellularis lesion: disrupting effects with electrolytic lesions and facilitative effects with excitotoxic lesions. To resolve this issue, in this experiment, Wistar rats received pre-training bilateral electrolytic or ibotenic acid lesions and were trained in a massed two-way active avoidance conditioning. In order to test the long-term retention of the learned response, one additional session was conducted 10 days after the acquisition. Results showed that whereas electrolytic lesions did not affect the acquisition, ibotenic acid lesions enhanced it. Retention of active avoidance response was impaired by both electrolytic and ibotenic lesions of the NBM. These results suggest a role of the NBM in the memory consolidation and/or retrieval of two-way active avoidance. Electronic Publication     

Rats with nucleus basalis magnocellularis lesions mimic mnemonic symptomatology observed in patients with dementia of the Alzheimer's type

College students, healthy elderly subjects, patients diagnosed with mild or moderate dementia of the Alzheimer's type, as well as rats with small or large lesions of nucleus basalis magnocellularis (NBM) were tested on an order memory task for a 6- or 8-item list of varying spatial locations. Similar patterns of order memory deficits as a function of serial order position were observed in rats with small or large NBM lesions and patients with mild or moderate dementia of the Alzheimer's type. The results provide support for the possibility that rats with NBM lesions might mimic the mnemonic symptomatology of Alzheimer's disease.     

Nucleus basalis lesions in neonate rats induce a selective cortical cholinergic hypofunction and cognitive deficits during adulthood

Summary Ibotenic acid was infused into the nucleus basalis magnocellularis (nBM) of 2-day old rats to eliminate immature cholinergic neurons before they develop functional synaptic connections in the neocortex. For bilaterally lesioned neonates, cognitive testing was initiated 2 months after lesioning and animals were sacrificed at 8 or 12 months of age. Lesioned animals exhibited a marked deficit in the retention of passive avoidance behavior, as well as in the acquisition of 2-way active avoidance behavior. Lesioned animals also made significantly more alternation errors than control animals in the Lashley III spatial maze and showed severe impairments in general learning, reference memory and working memory during 17-arm radial maze testing. For all 4 tasks, neonatally lesioned animals did not show any recovery to the performance level of control animals. Histological analysis of the subcortex from lesioned animals during adulthood revealed: (1) a substantial reduction in acetylcholinesterase-positive cells (presumably cholinergic) within the nucleus basalis, (2) decreased acetylcholinesterase staining in neocortex and (3) a gliosis essentially restricted to the globus pallidus. Surrounding brain regions were apparently not damaged as a direct result of excitotoxin infusion. Neurochemically, neonate nBM lesioning produced a long term cholinergic hypofunction as evidenced by significant reductions of 25% and 18% in frontal cortex chorine acetyltransferase (CAT) activity at 12 and 8 months of age, respectively. By contrast, prefrontal cortical concentrations of biogenic amines and their metabolites were unaffected, thus indicating a degree of neurochemical specificity for these neonatal nBM lesions. The persistant cortical cholinergic hypofunction in lesioned animals may be related to the long term deficits in learning/memory abilities that were also observed. It is suggested that neonatal nBM lesioning could provide a useful animal model for elucidating the plasticity of the developing brain after cortical anervation.     

Sleep-wake related discharge properties of basal forebrain neurons recorded with micropipettes in head-fixed rats

The basal forebrain has been shown to play an important role in cortical activation of wake and paradoxical sleep (PS), yet has also been posited to play a role in slow wave sleep (SWS). In an effort to determine whether these different roles may be fulfilled by different cell groups, including cholinergic and GABAergic cells, we recorded from 123 units in waking-sleeping, head-fixed rats using micropipettes to allow juxtacellular labeling. Functional sets of intermingled cell groups emerged as units whose discharge was as follows: 1) maximum in active wake (aW) and positively or not correlated with EEG gamma activity, while positively correlated with nuchal EMG activity, and thus potentially facilitatory for waking and behavioral arousal (12%); 2) maximum in SWS or SWS-PS and positively correlated with delta EEG activity, while not or negatively correlated with EMG activity, and thus potentially promotive for sleep with cortical slow wave activity and/or accompanying behavioral changes (16%); 3) maximum in PS or PS and aW and positively correlated with gamma and theta EEG activity, while negatively or not correlated with EMG activity, and thus potentially promotive for cortical activation during PS or PS and W (62%); and 4) equivalent across all states and thus not involved in state regulation ( approximately 10%). Units of each group also manifested different firing patterns typified as slow tonic (19.5%), fast tonic (32.5%), or fast phasic (48%), including rhythmic bursting (6%). Through these diverse cell groups, the basal forebrain has the capacity to modulate cortical activity, behavior, and/or related physiological processes across the sleep-waking cycle and thereby regulate the sleep-wake state of the animal.     

Effects of fornix lesions on waking and sleep patterns in white rats.

Polygraphic 12-hr daytime observation of male albino rats revealed increased spontaneous motor activity by a coronal fornical transection but not by a frontal cortical lesion. Fornicotomy alone affected sleep patterns by reducing the total time spent in slow wave sleep (SWS) and paradoxical sleep (PS) and in frequency of occurrence of SWS and PS and by increasing mean duration in the PS phase and the inter PS-interval. However, fornicotomy failed to affect the ratio of the two sleep phases (PS/SWS) either in total time, frequency of occurrence or duration and it did not alter the rate of tiny muscle twitching in PS. Since hippocampal theta activity was completely eliminated by the fornix lesions, the previously hypothesized relationship between theta activity and behaviors such as voluntary movement and PS is in need of revision.     

Individual differences in aging: behavioral and neurobiological correlates

The goal of this experiment was to determine the correlations among different behavioral and neurobiological measures in aged rats. Aged Sprague-Dawley rats were given a battery of cognitive and sensorimotor tests, followed by electrophysiological assessment of sleep and biochemical measurements of various neurotransmitter systems. The behavioral tests included the following: Activity level in an open field; short-term and long-term memory of a spatial environment as assessed by habituation: spatial navigation, discrimination reversal, and cue learning in the Morris water pool; spatial memory in a T-maze motivated by escape from water; spatial memory and reversal on the Barnes circular platform task; passive avoidance; motor skills. Sleep was assessed by electrographic cortical records. The following neurotransmitter markers were examined: Choline acetyltransferase; the density of nicotinic, benzodiazepine and glutamine receptors in the cortex and caudate nucleus; endogenous levels of norepinephrine, dopamine, and serotonin in the cortex and hippocampus. The duration of bouts of paradoxical sleep was strongly correlated with several cognitive measures and selected serotonergic markers. This finding suggests that changes in sleep patterns and brain biochemistry contribute directly to deficits in learning and memory, or that the same neurobiological defect contributes to age-related impairments in sleep and in learning and memory.