Research Briefs

Long-term potentiation in the rat hippocampus is reversibly depressed by chronic intermittent ethanol exposure.

M. Roberto, T.E. Nelson, C.L. Ur and D.L. Gruol (2002) Journal of Neurophysiology 87; 2385-2397

The hippocampus, which plays a significant role in memory formation, is a likely site for effects of alcohol in the brain. Both acute and chronic ethanol exposure have been shown to block the induction of Long-term potentiation (LTP) in the rat hippocampus. In fact, exposure to ethanol causes permanent changes in the hippocampus, most notably a reduction of neurons.

In this experiment, rats were exposed intermittently to alcohol vapor in order to facilitate alcohol consumption. LTP, which can be elicited experimentally by a brief high-frequency stimulation of presynaptic neurons, was found to be significantly reduced in the experimental animals compared to matched control animals that had not been exposed to ethanol. In a group of animals that was allowed to go through a five-day withdrawal period following alcohol exposure, the LTP response was only partially recovered.

Spatial, contextual and working memory are not affected by the absence of mossy fiber long-term potentiation and depression.

R.A. Hensbroek, A. Kamal, A.M. Baars, M. Verhage and B.M. Spruijt (2003) Behavioral Brain Research 138; 215-223
Granule cells of the dentate gyrus project via mossy fibers to the CA3 field of the hippocampus. Lesions in these cells impair spatial memory, and the acquisition of spatial memory is blocked by inactivation of mossy fibers. When NMDA receptor dependent LTP and LTD are blocked, animals are impaired in performance of the Morris water-maze. This is not the case, however, with mossy fiber pathways. Mossy fiber LTP and LTD, which are independent of NMDA-receptors, are apparently not necessary for the learning involved in spatial, contextual and working memory.

Research was conducted using Rab3A mutant mice deficient in a neuron-specific protein that is apparently necessary for both MF-LTP and MF-LTD. Spatial memory was tested in the eight arm radial maze, long-term spatial memory and spatial reversal learning in the Morris water-maze, and contextual memory in a fear conditioning task. There were no differences detected between performance of the mutant mice and matched controls in any of the three tasks. While certainly not conclusive, these results do indicate that mossy-fiber pathways are not necessary for spatial, contextual and working memory, at least not in the three paradigms used for this experiment.

Dependence on morphine leads to a prominent sharing among the different mechanisms of long-term potentiation in the CA1 region of rat hippocampus

Fereshteh Salmanzadeh, Yaghoub Fathollahi, Saeed Samnanian, Mahshid Shafizadeh and Anoushirvan Kazemnejad (2003) Brain Research 963; 93-100

Because opiate addiction is similar to learning processes, investigators sought to determine the role of morphine in LTP in the hippocampus. There is also evidence that exposure to opiates can impair performance on memory tasks, as well as indications that prenatal morphine exposure shifts the tendency of hippocampal synapses to favor Long-term depression. Schaffer collaterals of dependent rats to those demonstrated in hippocampal slices from a similar control group.

Results included a significant association between morphine dependence and LTP impairment. Apparently, dependence on morphine causes a shift in the synaptic plasticity threshold similar to that which occurs during aging. This shift could account for the memory and learning deficits apparent in morphine dependent individuals. Additionally, a tight coupling between NMDA and voltage dependent calcium influx regulation was observed.

Stress-related modulation of hippocampal long-term potentiation in rats: involvement of adrenal steroid receptors

Volker Korz and Julietta U. Frey (2003) The Journal of Neuroscience 23; 7281-7287

This study investigated the effects of different kinds of stress on the function of two corticosterone-binding receptors in the hippocampus. Activation of the glucocorticoid receptor (GR) impairs LTP while activation of the mineralocorticoid receptor (MR) facilitates LTP. Researchers used handling and swimming as models of stress to measure the effects that stress would have on LTP.

Results showed that stress caused by swimming prolonged LTP for up to 24 hours, while handling alone reversed early LTP. Administration of a GR antagonist prevented impairment of LTP in the handled group, although an MR antagonist had no effect. In contrast, the GR antagonist had no effect in the swimming condition, while the MR antagonist impaired LTP.

The researchers hypothesized that swim stress may lead to significant upregulation. It is also possible that the novelty of the environment, which has been implicated as a situation usually mediated by MR receptors, may have contributed to the LTP observed in the swimming condition.

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