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.
WHEN THE HIPPOCAMPAL CIRCUITS ARE DISTURBED
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
