To understand the complexity of memory and its loss, it is necessary to learn a bit about the hippocampus and its very complex structure and functions. This part of the ancient brain is crucial for the acquisition of new memories and transferring them to long term storage, called Long Term Potentiation, LTP
Unfortunately the hippocampus is also subject to many kinds of damage, including Amyloid deposition and atrophy in AD (JGW) exquisite susceptibility to ischemic damage after cardiac arrest, ischemia from stroke,(NWP) and inflammatory damage from herpes encephalitis that usually affects the temporal lobes. (Olyve) All of these conditions can cause various forms of memory loss/dysfunction. I will be adding more images and references to help clarify these. This is a section of hippocampus stained to show neurons from 1886, that show the architectural complexity needed for it's complex functions, and how easy it would be to disrupt them.
https://hekint.org/2019/11/21/staining-the-cells-of-the-nervous-system/TAT
The Hippocampus in health and disease: An overviewSince hippocampus receives direct inputs from olfactory bulb, it is important that it was implicated in olfaction for a long time.[18] Memory started dominating in early 1970s, with the description of LTP.[19] Anterograde and partial retrograde amnesia developed in a patient called Henry Gustav Molaison (called HM)[20] following removal of hippocampus due to refractory epilepsy. HM was unable to form new episodic memories following this surgery. In medical science, HM has been perhaps the most studied medical patient. Later studies have shown that damage to hippocampus causes anterograde amnesia and often retrograde amnesia also. Implicit memory is spared in hippocampal damage.[20,21]
Hippocampus is one of the unique regions in brain where the neurogenesis[22] continues even in adult life. Though, described initially, as “too little,†neurogenesis in brain is now thought to be functionally important. It has been seen that neurons, hence, produced integrate into the mainstream neurons. They have also, hence, shown to be functionally important. However, a recent review agreed that neurogenesis per se may be less attractive drug target[8] than hippocampal atrophy as a whole.
Hippocampus is now known not just to be important in learning and memory but also in:
Spatial navigation[24]
Emotional behavior[25]
Regulation of hypothalamic functions[27]
Learning and Memory: Hippocampus is vital for learning, memory, and spatial navigation. Connections between hippocampus and neocortex are important for awareness about conscious knowledge.[28] An intricate balance is maintained during encoding of memories in hippocampus and retrieval of experiences from frontal lobe. For learning and memory loop, there are two prominent pathways: polysynaptic and direct pathway. In polysynaptic pathway, hippocampus gets afferent connections from parietal, temporal, and occipital areas via entorhinal cortex and then to dentate gyrus→CA3→ CA1→ subiculum→ alveus→ fimbria→ fornix→ mammillothalamic tract→ anterior thalamus→ posterior cingulated→ retrosplenial cortex. In the direct intra-hippocampal pathway, it gets its input from temporal association cortex through perirhinal and entorhinal area to CA1. From there, projections move via subiculum and entorhinal crtex to inferior temporal cortex, temporal pole, and prefrontal cortex. It is important to remember that polysynaptic pathway is important in semantic memory while direct intra-hippocampal pathway is important in episodic and spatial memory.[28]
Other Roles: Hippocampus is a part of ventral striatal loop, hence can affect motor behavior.[30] Though emotional behavior is regulated mainly by amygdala, hippocampus and amygdala both have reciprocal connections, thus can influence each other (latter affects more than former). Since hippocampus has projections to hypothalamus, thus can affect release of adrenocorticotropic hormones. That is why, in patients with atrophied hippocampus, there is rise of cortisol.[27]
