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Memory and the brain
How Memory Works
Forgetting and Amnesia

The body’s adrenal glands produce two major types of hormones in response to stress. Catecholamines, such as adrenalin and norepinephrine, are produced by the adrenal medulla in response to an activation of the sympathetic nervous system. Glucocorticoids, including cortisol in humans and corticosterone in rats, are secreted by the adrenal cortex.

The effects of stress hormones on memory do not vary linearly with the plasmatic concentration of these hormones. Instead, these effects vary according to an inverted-U function. Moderately high concentrations seem to have an optimal effect, while lower or higher concentrations are accompanied by reduced plasticity.

The effects of glucocorticoids illustrate how physiological mechanisms are finely calibrated and operate within very narrow windows, in between total inertia and catastrophic excitation.

Linked Module: La mémoire qui flanche

At the cellular level, memory corresponds to the activation of certain networks of neurons.

The neural circuits of the hippocampus are among the most sensitive to the repeated stimuli that can strengthen such networks. So it is no surprise that many amnesias are associated with damage to the hippocampal circuits.

For example, the pyramidal cells of the hippocampus are highly sensitive to the adrenal hormones secreted in response to stress (see sidebar). These hormones can influence LTP, the mechanism that is the basis for memory, through receptors located directly on the neurons of the hippocampus.

The activation of these receptors has rapid effects on the release and re-uptake of glutamate in the hippocampal circuit, as well as slower effects on the metabolism of the cells, in particular as the result of the influx of more calcium into these neurons. Over the very long term, the morphology of the pyramidal cells is affected, either reversibly or irreversibly, depending on the duration and intensity of the stress.

The operation of the neural circuits of the hippocampus can also be disturbed by direct lesions. In the case of patient H.M., the complete ablation of both his hippocampi clearly had disastrous effects on his memory. But other patients who have suffered more subtle kinds of damage to certain regions of the hippocampus have also had memory problems. During an open-heart operation, patient R.B. suffered an ischemia (absence of blood flow) that caused damage to the pyramidal neurons in area CA1 of the hippocampus. As a result, this patient suffered pronounced anterograde amnesia along with minor retrograde amnesia.  

1- perforant path
2- mossy fibers
3- Schaffer collaterals
4- axons from CA1 pyramidal cells
5- axons from Subiculum cells

Certain encephalopathies, which lead to a degeneration of the neurons of the hippocampus, can also lead to amnesias.

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