Hippocampus
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Low frequency-induced short-term synaptic plasticity was investigated in hippocampal slices with 60-electrode recording array. Remarkably, the application of low-frequency stimulation (1 Hz) for a short duration (3-5 min) resulted in the induction of a slow-onset long-term potentiation (LTP) in the immediate vicinity of the stimulated electrode. This phenomenon was observed exclusively in the CA1 subfield, neither in the CA3 area nor in the dentate gyrus. ⋯ Although mitogen activated protein kinase pathway was stimulated after the application of low frequency, the induction and maintenance of this slow-onset LTP were not dependent on the activation of this intracellular pathway. The direct activation of adenylyl cyclase with forskolin also induced a synaptic enhancement displaying similar features. This new form of LTP could represent the mnesic engram of mild and repetitive stimulation involved in latent learning.
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Neural activity often becomes rhythmic during mental processing. But there has been no direct proof that rhythmicity, per se, is important for mental function. We assessed this issue in relation to the contribution of hippocampal theta-frequency rhythmicity to learning in the Morris water maze by blocking theta (and other septal inputs to the hippocampus) and then using electrical stimulation to restore rhythmicity. ⋯ The results suggest that the precise frequency of rhythmicity may be important for hippocampal function. Functional rhythmicity needs, therefore, to be included in neural models of cognitive processing. The success of our procedure also suggests that simple alterations of rhythmicity could be used to ameliorate deficits in learning and memory. (c) 2006 Wiley-Liss, Inc.
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Infants passively exposed to morphine or heroin through their addicted mothers usually develop characteristic withdrawal syndrome of morphine after birth. In such early life, the central nervous system exhibits significant plasticity and can be altered by various prenatal influences, including prenatal morphine exposure. Here we studied the effects of prenatal morphine exposure on postsynaptic density protein 95 (PSD-95), an important cytoskeletal specialization involved in the anchoring of the NMDAR and neuronal nitric oxide synthase (nNOS), of the hippocampal CA1 subregion from young offspring at postnatal day 14 (P14). ⋯ Collectively, the study demonstrates that maternal exposure to morphine decreases the magnitude of PSD-95, nNOS, the phosphorylation of CREB(Serine-133), and LTD expression in hippocampal CA1 subregion of young offspring (e.g., P14). Such alterations within the developing brain may play a role for subsequent neurological impairments (e.g., impaired performance of long-term learning and memory). The results raise a possibility that postsynaptic density proteins could serve an important role, at least in part, for the neurobiological pathogenesis in offspring from the morphine-addicted mother and provide tentative therapeutic strategy.
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Although most observers agree that the hippocampus has a critical role in learning and memory, there remains considerable debate about the precise functional contribution of the hippocampus to these processes. Two of the most influential accounts hold that the primary function of the hippocampus is to generate cognitive maps and to mediate episodic memory processes. The well-documented spatial firing patterns (place fields) of hippocampal neurons in rodents, along with the spatial learning impairments observed with hippocampal damage support the cognitive mapping hypothesis. ⋯ Since episodic memories, by definition, include information about the time and place where the episode occurred, contextual information is a necessary prerequisite for any episodic memory. Thus, place fields contribute importantly to episodic memory as part of the needed context representations. Additionally, recent findings indicate that hippocampal neurons differentiate contexts at progressively finer levels of detail, suggesting a hierarchical coding scheme which, if combined with temporal information, could provide a means of differentiating memory episodes.
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It has been proposed that declarative memories can be dependent on both an episodic and a semantic memory system. While the semantic system deals with factual information devoid of reference to its acquisition, the episodic system, characterized by mental time travel, deals with the unique past experience in which an event took place. Episodic memory is characteristically hippocampus-dependent. ⋯ However, when these features are expressed during an animal's behavior, the neuronal activity could merely be categorizing the present situation and could therefore reflect semantic memory rather than episodic memory. We propose that mental time travel is the key feature of episodic memory and that it should take a form, in the awake animal, similar to the replay of behavioral patterns of activity that has been observed in hippocampus during sleep. Using tasks designed to evoke episodic memory, one should be able to see memory reactivation of behaviorally relevant sequences of activity in the awake animal while recording from hippocampus and other cortical structures.