Effects of Caloric Restriction on Spatial Object Recognition Memory, Hippocampal Neuron Loss and Neuroinflammation in Aged Rats.

Age-related neurobiological changes significantly affect hippocampal structure and function, such that the main cognitive impairments associated with aging are related to the integrity of this brain structure, including the deterioration in spatial object recognition (SOR) memory. Previous studies have shown that intrinsic factors such as neuroinflammation, as well as lifestyle factors such as diet, can affect aging-associated brain functions and cognitive performance. In this regard, caloric restriction (CR) produces beneficial effects on health and life expectancy, although its ability to slow down age-dependent effects on cognitive decline and hippocampus (HPC) functioning remains unclear.

Effects of caloric restriction on monoaminergic neurotransmission, peripheral hormones, and olfactory memory in aged rats.

Aging is associated with a reduced ability to identify and discriminate scents, and olfactory dysfunction has been linked to preclinical stages of neurodegenerative diseases in humans. Moreover, emerging evidence suggests that smell-driven behaviors are regulated by hormones like insulin or leptin, and by metabolic parameters like glucose, which in turn may influence monoaminergic neurotransmission in brain areas related to cognition. Several studies have suggested that dietary interventions like caloric restriction (CR) can mitigate the age-induced decline in memory by modifying metabolic parameters and brain monoaminergic levels.

Caloric restriction modulates the monoaminergic and glutamatergic systems in the hippocampus, and attenuates age-dependent spatial memory decline.

The beneficial effects of caloric restriction (CR) on health and life expectancy are well documented, although its ability to slow down age-dependent cognitive decline and the underlying biochemical changes remains unclear. Therefore, the aim of this study was to investigate the effects of CR on spatial memory in aged Wistar rats, as well as on monoaminergic and glutamatergic neurotransmission in the hippocampus (HPC). As such, animals maintained on different dietary regimes were trained in the Morris Water Maze (MWM): old rats (24-27 months) maintained on a 30% CR diet from four months of age, old rats (24-27 months) with unrestricted access to food (Ad Libitum); and adult rats (3-4 months) with Ad Libitum access to food.

Intra-hippocampal D-cycloserine rescues decreased social memory, spatial learning reversal, and synaptophysin levels in aged rats.

Rationale: Aging is characterized by a decrease in N-methyl-D-aspartate receptors (NMDARs) in the hippocampus, which might be one of the factors involved in the age-dependent cognitive decline. D-Cycloserine (DCS), a partial agonist of the NMDAR glycine recognition site, could improve memory deficits associated to neurodegenerative disorders and cognitive deficits observed in normal aging.

Objectives And Methods: The aim of the present study was to explore whether DCS would reverse age-dependent memory deficits and decreases in NMDA receptor subunits (GluN1, GluN2A, and GluN2B) and the presynaptic protein synaptophysin in Wistar rats.

Parafascicular thalamic nucleus deep brain stimulation decreases NMDA receptor GluN1 subunit gene expression in the prefrontal cortex.

The rodent parafascicular nucleus (PFn) or the centromedian-parafascicular complex of primates is a posterior intralaminar nucleus of the thalamus related to cortical activation and maintenance of states of consciousness underlying attention, learning and memory. Deep brain stimulation (DBS) of the PFn has been proved to restore arousal and consciousness in humans and to enhance performance in learning and memory tasks in rats. The primary expected effect of PFn DBS is to induce plastic changes in target neurons of brain areas associated with cognitive function.

[Oxytocin in the treatment of the social deficits associated to autism spectrum disorders].

Introduction: The recent involvement of oxytocin in social behavior of animals and humans has motivated the study of its effects on the social behavior of individuals with autism spectrum disorders (ASD).

Aims: To review the current state of oxytocin studies concerning its therapeutic potential in treating social deficits of the ASD population, and to establish likely future directions to be taken by the studies in this field.

Development: Some studies have linked oxytocin to the pathophysiology of autistic disorders.

D-cycloserine prevents relational memory deficits and suppression of long-term potentiation induced by scopolamine in the hippocampus.

Previous research has demonstrated that systemic D-cycloserine (DCS), a partial agonist of the N-methyl-D-aspartate receptor (NMDAR), enhances memory processes in different learning paradigms and attenuates mnemonic deficits produced by diverse pharmacological manipulations. In the present study two experiments were conducted in rats to investigate whether DCS administered in the hippocampus may rescue relational memory deficits and improve deficient synaptic plasticity, both induced by an intracerebral injection of the muscarinic receptor antagonist scopolamine (SCOP). In experiment 1, we assessed whether DCS would prevent SCOP-induced amnesia in an olfactory learning paradigm requiring the integrity of the cholinergic system, the social transmission of food preference (STFP).

D-cycloserine in prelimbic cortex reverses scopolamine-induced deficits in olfactory memory in rats.

A significant interaction between N-methyl-D-aspartate (NMDA) and muscarinic receptors has been suggested in the modulation of learning and memory processes. The present study further investigates this issue and explores whether d-cycloserine (DCS), a partial agonist at the glycine binding site of the NMDA receptors that has been regarded as a cognitive enhancer, would reverse scopolamine (SCOP)-induced amnesia in two olfactory learning tasks when administered into the prelimbic cortex (PLC). Thus, in experiment 1, DCS (10 µg/site) was infused prior to acquisition of odor discrimination (ODT) and social transmission of food preference (STFP), which have been previously characterized as paradigms sensitive to PLC muscarinic blockade.

The AMPA receptor modulator S18986 in the prelimbic cortex enhances acquisition and retention of an odor-reward association.

Systemic administration of S18986, a positive allosteric modulator of AMPA receptors, improves cognition. The present study further characterizes the drug's memory-enhancing properties and is the first to investigate its intracerebral effects on learning and memory. The results showed that rats receiving a single dose of S18986 (3 μg/site) into the prelimbic cortex, prior to olfactory discrimination acquisition, exhibited significantly shorter latencies and fewer errors to make the correct response, both in the acquisition and two drug-free retention tests.

D-cycloserine in the basolateral amygdala prevents extinction and enhances reconsolidation of odor-reward associative learning in rats.

It is well established that D-cycloserine (DCS), a partial agonist of the NMDA receptor glycine site, enhances learning and memory processes. Although the effects of DCS have been especially elucidated in the extinction and reconsolidation of aversive behavioral paradigms or drug-related behaviors, they have not been clearly determined in appetitive tasks using natural reinforcers. The current study examined the effects of pre-retrieval intra-basolateral amygdala (BLA) infusions of DCS on the extinction and reconsolidation of an appetitive odor discrimination task.

Learning deficits in an odor reward-task induced by parafascicular thalamic lesions are ameliorated by pretraining D-cycloserine in the prelimbic cortex.

We investigated whether the N-methyl-D-aspartate (NMDA) receptor partial agonist D-cycloserine (DCS) infused into the prelimbic cortex (PLC) would reverse the learning deficits caused by bilateral excitotoxic lesions of the parafascicular nucleus (PFn) in an odor discrimination task (ODT). Rats with PFn lesions received a bilateral infusion of DCS (10 μg/side) into the PLC 20 min before ODT acquisition. The task retention was evaluated in a drug-free test carried out 24 h later.

Effects of muscarinic receptor antagonism in the basolateral amygdala on two-way active avoidance.

The aim of the present study was to investigate whether the blockade of muscarinic receptors (mRs) in the basolateral amygdala (BLA), which receives important cholinergic inputs related to avoidance learning, affects the consolidation of two-way active avoidance (TWAA). In Experiment 1, adult male Wistar rats were bilaterally infused with scopolamine (SCOP, 20 μg/site) or PBS (VEH) in the BLA immediately after a single 30-trial acquisition session. Twenty-four hours later, avoidance retention was tested in an identical session.

D-cycloserine in prelimbic cortex enhances relearning of an odor-reward associative task.

We investigated the effects of bilateral infusions in the prelimbic cortex of D-cycloserine (DCS), a partial agonist of the NMDA receptor-associated glycine site. Wistar rats underwent a training session (acquisition, three trials) and a 24-h test (two retention and two relearning trials) of a rapidly learned olfactory discrimination task. Rats infused with DCS (10 microg/site) prior to training exhibited a significant enhancement of performance in such odor-reward task, especially in relearning.

Induction of c-Fos expression by electrical stimulation of the nucleus basalis magnocellularis.

The present study examined the expression of the immediate-early gene c-fos in different brain regions following a single 20-min session of unilateral electrical stimulation of the nucleus basalis magnocellularis (NBM). Current findings confirm that NBM stimulation provides specific activation of several cortical and subcortical regions closely related to the NBM and involved in learning and memory processes, such as the cingulate, parietal, piriform and perirhinal cortices, dorsal subiculum, and the parafascicular, central lateral and central medial nuclei of the thalamus. In contrast, NBM stimulation did not increase c-Fos expression in some expected areas that receive direct NBM projections such as the entorhinal cortex or amygdala nuclei.

Muscarinic receptor blockade in ventral hippocampus and prelimbic cortex impairs memory for socially transmitted food preference.

Acetylcholine is involved in learning and memory and, particularly, in olfactory tasks, but reports on its specific role in consolidation processes are somewhat controversial. The present experiment sought to determine the effects of blocking muscarinic cholinergic receptors in the ventral hippocampus (vHPC) and the prelimbic cortex (PLC) on the consolidation of social transmission of food preference, an odor-guided relational task that depends on such brain areas. Adult male Wistar rats were bilaterally infused with scopolamine (20 microg/site) immediately after social training and showed impairment, relative to vehicle-injected controls, in the expression of the task measured 24 h after learning.

Muscarinic transmission in the basolateral amygdala is necessary for the acquisition of socially transmitted food preferences in rats.

We examined the involvement of muscarinic receptors in the basolateral amygdala (BLA) in the social transmission of food preference (STFP) learning by assessing the effects of scopolamine (20 microg/side), injected prior to social training, on a 24-h food-choice test. Muscarinic receptor blockade in the BLA significantly impaired STFP, as shown by the rats' chance preference for the odorized trained food. The present results are consistent with the suggestion that intact cholinergic transmission in the BLA is necessary for acquisition and/or initial consolidation and provide evidence that BLA integrity is part of the underlying circuit of STFP learning.

Differential effects of muscarinic receptor blockade in prelimbic cortex on acquisition and memory formation of an odor-reward task.

The present experiments determined the consequences of blocking muscarinic cholinergic receptors of the prelimbic (PL) cortex in the acquisition and retention of an odor-reward associative task. Rats underwent a training test (five trials) and a 24-h retention test (two retention trials and two relearning trials). In the first experiment, rats were bilaterally infused with scopolamine (20 or 5 microg/site) prior to training.

Effects of parafascicular excitotoxic lesions on two-way active avoidance and odor-discrimination.

To investigate whether the parafascicular (PF) nucleus of the thalamus is involved in different learning and memory tasks, two experiments were carried out in adult male Wistar rats that were submitted to pre-training bilateral N-methyl-d-aspartate PF infusions (0.15M, pH 7.4; 1.

Muscarinic cholinergic receptor blockade in the rat prelimbic cortex impairs the social transmission of food preference.

Previous findings demonstrate the involvement of the cholinergic NBM in the acquisition of the social transmission of food preference (STFP), a relational associative odor-guided learning task. There is also evidence that muscarinic receptors in the medial prefrontal cortex, an important NBM target area, may modulate olfactory associative memory. The present experiment determined the consequences of blocking muscarinic cholinergic receptors in a component of the medial prefrontal region (the prelimbic cortex) on the STFP task.

Effects of nucleus basalis magnocellularis stimulation on a socially transmitted food preference and c-Fos expression.

Experiment 1 examined the effects of electrical stimulation of nucleus basalis magnocellularis (NBM) on a relational odor-association task--the social transmission of food preference (STFP). Rats were stimulated unilaterally in the NBM for 20 min (100 microA, 1 Hz) immediately before the social training. They were tested on their ability to remember preference for the trained food either immediately or following a 24-h delay.

Excitotoxic lesions of the parafascicular nucleus produce deficits in a socially transmitted food preference.

The parafascicular (PF) nucleus, a posterior component of the intralaminar nuclei of the thalamus, is considered to be an essential structure in the feedback circuits of basal ganglia-thalamo-cortical systems that critically participate in cognitive processes. To study the PF contribution to processing of behaviorally significant information during specific episodes of learning, we investigated the effects of damaging the PF nucleus in the acquisition of a natural form of social olfactory learning, the socially transmitted food preference (STFP) task. This task is a non-spatial paradigm that exhibits some of the characteristics of relational memory because it requires that animals use information obtained in one episode to guide later behavior in different circumstances.

Effects of electrical stimulation of the nucleus basalis on two-way active avoidance acquisition, retention, and retrieval.

This study assessed the role of the nucleus basalis magnocellularis (NBM) in specific memory phases of two-way active avoidance conditioning. We evaluated the effects of NBM electrical stimulation applied during different phases of the avoidance task. Rats were trained in a 30-trial acquisition session, and were tested again 24 and 48 h later.

Parafascicular electrical stimulation attenuates nucleus basalis magnocellularis lesion-induced active avoidance retention deficit.

Previous experiments from our laboratory showed that retention of two-way active avoidance learning is improved by post-training intracranial electrical stimulation (ICS) of the parafascicular nucleus (PF) and impaired by pre-training electrolytic lesions of the nucleus basalis magnocellularis (NBM). The question investigated here was whether post-training PF ICS is able to attenuate the active avoidance retention deficit observed in rats lesioned pre-training in the NBM. To this goal, the following experimental design was used: rats bilaterally lesioned in the NBM and stimulated in the PF, rats lesioned in the NBM, rats stimulated in the PF, control rats implanted in the PF, and sham-operated rats were first trained in a shuttle-box for a single 30-trial session and tested again following two successive retention intervals (24 h and 11 days).

Effects of fimbria lesions on trace two-way active avoidance acquisition and retention in rats.

The fimbria-fornix (FF) is the main subcortical input to the hippocampus. It has been shown that FF lesions facilitate performance on a standard-delay two-way active avoidance task (AA2), thought to involve implicit memory. The hippocampal region is required for explicit or relational memory.

Selective lesions of basal forebrain cholinergic neurons produce anterograde and retrograde deficits in a social transmission of food preference task in rats.

We examined the performance of Long-Evans rats with 192 IgG-saporin lesions of the medial septum/vertical limb of the diagonal band (MS/VDB) or nucleus basalis magnocellularis/substantia innominata (NBM/SI), which removed cholinergic projections mainly to hippocampus or neocortex, respectively. We studied the effects of these lesions on anterograde and retrograde memory for a natural form of hippocampal-dependent associative memory, the social transmission of food preference. In a study of anterograde memory, MS/VDB lesions did not affect the immediate, 24-h or 3-week retention of the task.