No abstract

The hippocampus is well known for its critical involvement in spatial memory and information processing. In this study, we examined the effect of bilateral hippocampal inactivation with tetrodotoxin (TTX) in an "enemy avoidance" task. In this paradigm, a rat foraging on a circular platform (82 cm diameter) is trained to avoid a moving robot in 20-min sessions. Whenever the rat is located within 25 cm of the robot's center, it receives a mild electrical foot shock, which may be repeated until the subject makes an escape response to a safe distance. Seventeen young male Long-Evans rats were implanted with cannulae aimed at the dorsal hippocampus 14 d before the start of the training. After 6 d of training, each rat received a bilateral intrahippocampal infusion of TTX (5 ng in 1 μL) 40 min before the training session on day 7. The inactivation severely impaired avoidance of a moving robot (n = 8).No deficit was observed in a different group of rats (n = 9) that avoided a stable robot that was only displaced once in the middle of the session, showing that the impairment was not due to a deficit in distance estimation, object-reinforcement association, or shock sensitivity. This finding suggests a specific role of the hippocampus in dynamic cognitive processes required for flexible navigation strategies such as continuous updating of information about the position of a moving stimulus.cognitive map | declarative memory | episodic memory | dynamic environments R esearch into the hippocampal role in behavior and cognition is marked by a lasting dichotomy between two major views based on studies on laboratory rodents on one side and studies on human subjects or subhuman primates on the other. Electrophysiological recordings from hippocampus of freely moving rodents showed that many pyramidal neurons act as "place cells" signaling the position of the animal within an environment (1, 2). Based on these findings, the cognitive map theory (3) postulated that the hippocampus provides an allothetic spatial representation of the environment. Further support for this theory came from lesion studies showing detrimental effects of hippocampal lesions on spatial behavior (4-6). However, damage to the hippocampus and surrounding medial temporal lobe structures produce permanent anterograde amnesia for facts and autobiographical events in humans (7). Based on this evidence, the declarative memory theory presumes that the hippocampus is responsible for creating memory representations for these classes of information, which later become hippocampus-independent in a process called systems consolidation (8,9). This theory is supported by studies on recognition memory (10) and models of amnesia (11) in primates. However, the declarative memory theory does not predict lasting hippocampal involvement in some behavioral tasks such as the spatial water maze (12-16). However, the cognitive map theory does not explain hippocampal role in overtly nonspatial memory tasks (17). In a shadow of these two major theories, minor views claim that the ...

The pathogenesis of Alzheimer’s disease (AD), the most prevalent form of dementia, remains unclear. Over the past few years, evidence has accumulated indicating that perturbed cerebral bioenergetics and neuroinflammation may compromise cognitive functions and precedes the onset of AD and that impaired function of glial cells can likely contribute to the development of the disease. Recently, N6-methyladenosine (m6A) modification of RNA has been implicated in the regulation of different processes in the brain and to play a potential role in neurodegeneration. In the present study, we investigated the potential role of the m6A machinery enzymes in a streptozotocin (STZ) model of AD in human astrocytoma CCF-STTG1 cells. We observed that STZ-treated astrocytes expressed significantly higher levels of m6A demethylase fat mass and obesity-associated protein (FTO) and m6A reader YTHDF1 (YTH domain-containing family protein 1). Our experiments revealed that MO-I-500, a novel pharmacological inhibitor of FTO, can strongly reduce the adverse effects of STZ. Inhibition of FTO enhanced the survival of cells exposed to STZ and suppressed oxidative stress, apoptosis, elevated expression of glial fibrillary acidic protein, mitochondrial dysfunction, and bioenergetic disturbances induced by this compound. Overall, the results of this study indicate that perturbed m6A signaling may be contributing to AD pathogenesis, likely by compromising astrocyte bioenergetics.