Biomedical subjects

Daniela M Barros

Publications and source records attributed to Daniela M Barros.

8 recordsLinked to original sources

PubMed2006

Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition.

An important step for cholinergic transmission involves the vesicular storage of acetylcholine (ACh), a process mediated by the vesicular acetylcholine transporter (VAChT). In order to understand the physiological roles of the VAChT, we developed a genetically altered strain of mice with reduced expression of this transporter. Heterozygous and homozygous VAChT knockdown mice have a 45% and 65% decrease in VAChT protein expression, respectively. VAChT deficiency alters synaptic vesicle filling and affects ACh release. Whereas VAChT homozygous mutant mice demonstrate major neuromuscular deficits, VAChT heterozygous mice appear normal in that respect and could be used for analysis of central cholinergic function. Behavioral analyses revealed that aversive learning and memory are not altered in mutant mice; however, performance in cognitive tasks involving object and social recognition is severely impaired. These observations suggest a critical role of VAChT in the regulation of ACh release and physiological functions in the peripheral and central nervous system.

Acetylcholine↗

PubMed2005

Retrieval and the extinction of memory.

1. Memory is assessed by measuring retrieval which is often elicited by the solely presentation of the conditioned stimulus (CS). However, as known since Pavlov, presentation of the CS alone generates extinction. 2. One-trial avoidance (IA) is a much used conditioned fear paradigm in which the CS is the safe part of a training apparatus, the unconditioned stimulus (US) is a footshock and the conditioned response (CR) is to stay in the safe area. Retrieval of the memory for the step-down version of this task is measured in the absence of the US, as latency to step-down from the safe area (i.e., a platform). 3. Extinction of the IA response is installed at the moment of the first non-reinforced test session, as clearly shown by the fact that many drugs, including PKA, ERK and protein synthesis inhibitors as well as NMDA receptor antagonists, hinder extinction when infused into the hippocampus or the basolateral amygdala at the moment of the first test session but not later. 4. Some, but not all the molecular systems required for extinction are also activated by retrieval, further endorsing the hypothesis that although retrieval is necessary for the generation of extinction this last process constitutes a new learning secondary to the non-reinforced expression of the original trace.

Animals↗

PubMed2004

The transition from memory retrieval to extinction.

Memory is measured by measuring retrieval. Retrieval is often triggered by the conditioned stimulus (CS); however, as known since Pavlov, presentation of the CS alone generates extinction. One-trial avoidance (IA) is a much used conditioned fear paradigm in which the CS is the safe part of a training apparatus, the unconditioned stimulus (US) is a footshock and the conditioned response is to stay in the safe area. In IA, retrieval is measured without the US, as latency to step-down from the safe area (i.e., a platform). Extinction is installed at the moment of the first unreinforced test session, as clearly shown by the fact that many drugs, including PKA, ERK and protein synthesis inhibitors as well as NMDA receptor antagonists, hinder extinction when infused into the hippocampus or the basolateral amygdala at the moment of the first test session but not later. Some, but not all the molecular systems required for extinction are also activated by retrieval, further endorsing the hypothesis that although retrieval is behaviorally and biochemically necessary for the generation of extinction, this last process constitutes a new learning secondary to the unreinforced expression of the original trace.

Animals↗

PubMed2003

The effects of aging on leukocyte glucocorticoid receptor concentration and response to dexamethasone in dogs.

Glucocorticoid receptor concentration (GR) was determined in mononuclear (MNS) and polymorphonuclear (PMNS) cells isolated from 8 aged and 9 young male dogs. In addition, leukocyte responses to dexamethasone (0.1 mg kg(-1) i.v.) and plasma glucose concentration were also measured. The GR in MNS and PMNS was higher (p<0.05) in young dogs (6.64 +/- 0.57 and 7.04 +/- 0.29 fmolesx10(6) cells, respectively, versus 4.40 +/- 0.24 and 5.06 +/- 0.33 fmolesx10(6) cells, respectively, in aged dogs). The maximum increase in neutrophils (DeltaNEU) was lower (p<0.05) in aged dogs 6003.38 +/- 1398.5x10(6) versus 11168.67 +/- 1863.16x10(6) cells l(-1) in young dogs. The maximum decrease in lymphocytes (DeltaLYM) was lower (p<0.05) in aged dogs 550 +/- 56.75x10(6) cells l(-1) versus 1825.89 +/- 313.1x10(6) cells l(-1) in young dogs. In young dogs, significant (p<0.05) correlations between GR in PMNS and DeltaNEU (r=0.80) and between GR in MNS and DeltaLYM (r=0.76) were observed. In aged dogs, these correlations were not significant. The lower GR value and the lack of correlation between this parameter and its respective Delta in aged dogs suggest that changes in leukocytes responsiveness to glucocorticoids is occurring during the aging process.

Aging↗

PubMed2003

Exposure to novelty enhances retrieval of very remote memory in rats.

Rats were trained in a one-trial step-down inhibitory avoidance task at the age of 3 months and tested for retention 1 day later, or 3, 6, 9, 12, 15, and 19 months later, i.e., when the animals were 3, 6, 9, 12, 15, 18, or 22 months of age. Retrieval performance declined with time and was undetectable in the last two age groups. Exposure to an unrelated novel environment (a square box lined with black plastic) 1 h before retention testing enhanced retrieval at all ages, regardless of the decline in the level of test session performance. The effect cannot be explained by an anxiogenic effect of the novelty box, or by an influence of novelty on locomotion or exploration, or by a nonspecific influence of exposure to novelty on step-down latency in the inhibitory avoidance apparatus.

Animals↗

PubMed2003

Pharmacological findings contribute to the understanding of the main physiological mechanisms of memory retrieval.

Recent pharmacological findings have shown that retrieval of one-trial avoidance learning requires glutamate receptors, cAMP-dependent protein kinase and mitogen-activated protein kinases in the hippocampus, entorhinal, posterior parietal and anterior cingulate cortex. It requires AMPA but not other type of glutamate receptors or the protein kinases in the amygdala. Retrieval is modulated by dopamine D1, beta-noradrenergic, serotonin 1A and cholinergic receptors in the four cortical structures mentioned, and by beta-noradrenergic receptors in the basolateral amygdala. Further, retrieval is also modulated by peripheral ACTH, glucocorticoids, vasopressin, beta-endorphin and catecholamines; these hormones probably act through beta-noradrenergic receptor systems in the basolateral amygdala. Exposure to novelty or the systemic administration of antidepressant drugs prior to retention tests enhances retrieval, even for very remote memories. The effect of novelty is mediated by molecular mechanisms similar to those of retrieval itself.

Animals↗

PubMed2002

Molecular pharmacological dissection of short- and long-term memory.

1. It has been discussed for over 100 years whether short-term memory (STM) is separate from, or just an early phase of, long-term memory (LTM). The only way to solve this dilemma is to find out at least one treatment that blocks STM while keeping LTM intact for the same task in the same animal. 2. The effect of a large number of treatments infused into the hippocampus, amygdala, and entorhinal, posterior parietal or prefrontal cortex on STM and LTM of a one-trial step-down inhibitory avoidance task was studied. The animals were tested at 1.5 h for STM, and again at 24 h for LTM. The treatments were given after training. 3. Eleven different treatments blocked STM without affecting LTM. Eighteen treatments affected the two memory types differentially, either blocking or enhancing LTM alone. Thus, STM is separate from, and parallel to the first hours of processing of, LTM of that task. 4. The mechanisms of STM are different from those of LTM. The former do not include gene expression or protein synthesis; the latter include a double peak of cAMP-dependent protein kinase activity, accompanied by the phosphorylation of CREB, and both gene expression and protein synthesis. 5. Possible cellular and molecular events that do not require mRNA or protein synthesis should account for STM. These might include a hyperactivation of glutamate AMPA receptors, ribosome changes, or the exocytosis of glycoproteins that participate in cell addition.

Animals↗

PubMed2002

Molecular mechanisms of memory retrieval.

Memory retrieval is a fundamental component or stage of memory processing. In fact, retrieval is the only possible measure of memory. The ability to recall past events is a major determinant of survival strategies in all species and is of paramount importance in determining our uniqueness as individuals. Most biological studies of memory using brain lesion and/or gene manipulation techniques cannot distinguish between effects on the molecular mechanisms of the encoding or consolidation of memories and those responsible for their retrieval from storage. Here we examine recent findings indicating the major molecular steps involved in memory retrieval in selected brain regions of the mammalian brain. Together the findings strongly suggest that memory formation and retrieval may share some molecular mechanisms in the hippocampus and that retrieval initiates extinction requiring activation of several signaling cascades and protein synthesis.

Animals↗