Diferenças funcionais das regiões hipocampais na formação da memória do tipo o quê", "quando" e "onde" em ratos

Episodic memory refers to the recollection of what, where and when a specific event occurred. Hippocampus is a key structure in this type of memory. Computational models suggest that the dentate gyrus (DG) and the CA3 hippocampal subregions are involved in pattern separation and the rapid acquisition of episodic memories, while CA1 is involved in memory consolidation. However there are few studies with animal models that access simultaneously the aspects ‗what-where-when . Recently, an object recognition episodic-like memory task in rodents was proposed. This task consists of two sample trials and a test phase. In sample trial one, the rat is exposed to four copies of an object. In sample trial two, one hour later, the rat is exposed to four copies of a different object. In the test phase, 1 h later, two copies of each of the objects previously used are presented. One copy of the object used in sample trial one is located in a different place, and therefore it is expected to be the most explored object.However, the short retention delay of the task narrows its applications. This study verifies if this task can be evoked after 24h and whether the pharmacological inactivation of the DG/CA3 and CA1 subregions could differentially impair the acquisition of the task described. Validation of the task with a longer interval (24h) was accomplished (animals showed spatiotemporal object discrimination and scopolamine (1 mg/kg, ip) injected pos-training impaired performance). Afterwards, the GABA agonist muscimol, (0,250 μg/μl; volume = 0,5 μl) or saline were injected in the hippocampal subregions fifteen minutes before training. Pre-training inactivation of the DG/CA3 subregions impaired the spatial discrimination of the objects (‗where ), while the temporal discrimination (‗when ) was preserved. Rats treated with muscimol in the CA1 subregion explored all the objects equally well, irrespective of place or presentation time. Our results corroborate the computational models that postulate a role for DG/CA3 in spatial pattern separation, and a role for CA1 in the consolidation process of different mnemonic episodes

Efeitos dos esteroides anabólicos androgênicos sobre funções cognitivas de ratos

The use and the demand for substances that enhance masculinity, strength and sexual power are not novel. Over the years, this search has assisted the research directions in this area, leading to the discovery of the primary male sex hormone testosterone in 1935. Since then, numerous testosterone analogue compounds were synthesized, which are generically called Anabolic Androgenic Steroids (AAS). The AAS were produced for therapeutic purposes, but an increase in the use of these compounds for other purposes occurred over time. Initially they were used mainly to improve performance in athletes. However, recent studies have shown that the use of AAS by non-athletes with aesthetical purposes have been increasing as well. The abuse of AAS with non-clinical purposes can promote a number of physiological alterations, such as heart, liver, respiratory and psychological problems such as changes in mood, levels of anxiety and aggression. Exposure to supraphysiological doses of AAS is associated with behavioral changes, however, little is known about the effects of AAS on cognitive functions. In this work, we aimed to mimic the AAS abuse in humans with intramuscular administration of a supraphysiological dose of testosterone propionate (TP) in rats. We investigated the effects of this treatment on different aspects of cognitive function, specifically learning, memory and anxiety. Adult male Wistar rats were tested in the spontaneous alternation, novel object recognition and plus-maze discriminative avoidance tasks. The control group received intramuscular injections of vegetable oil (vehicle), and the TP group received injections of TP (10 mg/kg, i.m.). The injections were administered for 40 days, with intervals of 48 hours (chronic treatment) or in a single injection (acute treatment). In addition to the behavioral assessments, we performed biochemical analyzes as indicators of the endocrine effects of the treatment. Our results show that chronic treatment with a supraphysiological dose of TP caused memory impairments in the novel object recognition and the discriminative avoidance tasks. The spatial working memory (evaluated by spontaneous alternation task) was not affected. Also, we did not observe changes in anxiety levels. Regarding the biochemical parameters, chronic treatment increased serum levels of glutamicpyruvic transaminase, an indicator of hepatic and pancreatic lesions (as those observed after chronic use of these substances in humans). On the other hand, acute treatment with PT did not promote significant changes in any of these parameters when compared to the control group. In summary, we conclude that chronic treatment with a supraphysiological dose of testosterone propionate produces memory deficits in novel object recognition and retrieval of the discriminative avoidance task in adult male rats

Déficits de memória induzidos por baixas doses de reserpina em ratos: possível relação com prejuízos no processamento emocional na Doença de Parkinson

We have recently verified that the monoamine depleting drug reserpine at doses that do not modify motor function - impairs memory in a rodent model of aversive discrimination. In this study, the effects of reserpine (0.1-0.5 mg/kg) on the performance of rats in object recognition, spatial working memory (spontaneous alternation) and emotional memory (contextual freezing conditioning) tasks were investigated. While object recognition and spontaneous alternation behavior were not affected by reserpine treatment, contextual fear conditioning was impaired. Together with previous studies, these results suggest that mild monoamine depletion would preferentially induce deficits in tasks involved with emotional contexts. Possible relationships with cognitive and emotional processing deficits in Parkinson disease are discussed

Alterações do ciclo sono-vigília moduladas por Dopamina e suas consequências Mnemônicas

Neuroscience is on a rise of discoveries. Its wide interdisciplinary approach facilitates a more complex understanding of the brain, covering various areas in depth. However, many phenomena that fascinate human kind are far from being fully elucidated, such as the formation of memories and sleep. In this study we investigated the role of the dopaminergic system in the process of memory consolidation and modulation of the phases of sleep-wake cycle. We used two groups of animals: wildtype mice and hiperdopaminergic mice, heterozygous for the gene encoding the dopamine transporter protein. We observed in wild-type mice that the partial blockade of the D2 dopamine receptor by the drug haloperidol caused deficits in memory consolidation for object recognition, as well as a significant reduction in the duration of rapid eye movement sleep (REM). We also found a mnemonic deficit without pharmacological intervention in hiperdopaminergic animals; this deficit was reversed with haloperidol. The results suggest that dopamine plays a key role in memory consolidation for object recognition. The data also support a functional relationship between the dopaminergic system and the modulation of REM sleep

Efeitos da privação do sono em tarefas cognitivas

Learning and memory are important mechanism for species, since its allows to recognize conspecifics, routes and food place. Sleep is one of behaviors known by facilitate learning, it is a widespread phenomenon, present in most of vertebrates lives and highly investigated in many aspects. It is known that sleep deprivation modifies physiologic behavioral processes in animals, however, sleep function in organism is still debatable. Hypothesis range from energy conservation to memory consolidation, with different roles in animal’s evolution. The zebrafish (Danio rerio) emerg e in the last years as vertebrate model in genetics and developmental biology and quickly become popular in behavioral studies, as learning and memory. Despite the fact that zebrafish is a diurnal animal and have well characterized sleep behavior, zebrafish fish still has advantages due to its small size and low cost of maintenance, whichestablishes this species as interesting model for research on sleep. In this study we aimed to analyze the effects of partial and total sleep deprivation on learning acquisition, as well the concomitant administration of alcohol and melatonin. For this, the research was divided in three phases, each one with a different kind of conditioning: (1) object Recognition, (2) avoidance conditioning and (3) appetitive conditioning. The results showed the fish partially sleep deprived and totally sleep deprived + et hanol could perform the tasks just like the control group, however, fish totally sleep deprived and totally sleep deprived + melatonin showed impairments in attention and memory during the tests. Our results suggest that only one night of sleep deprivation is enough to harm the zebrafish performance in cognitive tasks. In addition, ethanol exposure on the night previously the test seems to suppress the negative effects of sleep deprivation, while the melatonin treatment seems not to be enough to promote sleep state, at least on the protocol applied here.

Efeitos da privação do sono em tarefas cognitivas

Learning and memory are important mechanism for species, since its allows to recognize conspecifics, routes and food place. Sleep is one of behaviors known by facilitate learning, it is a widespread phenomenon, present in most of vertebrates lives and highly investigated in many aspects. It is known that sleep deprivation modifies physiologic behavioral processes in animals, however, sleep function in organism is still debatable. Hypothesis range from energy conservation to memory consolidation, with different roles in animal’s evolution. The zebrafish (Danio rerio) emerg e in the last years as vertebrate model in genetics and developmental biology and quickly become popular in behavioral studies, as learning and memory. Despite the fact that zebrafish is a diurnal animal and have well characterized sleep behavior, zebrafish fish still has advantages due to its small size and low cost of maintenance, whichestablishes this species as interesting model for research on sleep. In this study we aimed to analyze the effects of partial and total sleep deprivation on learning acquisition, as well the concomitant administration of alcohol and melatonin. For this, the research was divided in three phases, each one with a different kind of conditioning: (1) object Recognition, (2) avoidance conditioning and (3) appetitive conditioning. The results showed the fish partially sleep deprived and totally sleep deprived + et hanol could perform the tasks just like the control group, however, fish totally sleep deprived and totally sleep deprived + melatonin showed impairments in attention and memory during the tests. Our results suggest that only one night of sleep deprivation is enough to harm the zebrafish performance in cognitive tasks. In addition, ethanol exposure on the night previously the test seems to suppress the negative effects of sleep deprivation, while the melatonin treatment seems not to be enough to promote sleep state, at least on the protocol applied here.