3.9: Memory

The investigation of a renowned case involving a patient named Henry Molaison, referred to as HM, who underwent bilateral removal of his medial temporal lobes to mitigate intractable epilepsy illuminated the intricate association between brain structures and memory function. After the 1953 bilateral lobectomy, which alleviated his epilepsy but rendered HM incapable of forming new memories—a condition termed anterograde amnesia—he could recall most events predating the surgery, though experiencing partial loss of earlier memories, defined as retrograde amnesia. This circumstance catalyzed comprehensive investigations into memory mechanisms.

Although many questions are unanswered, memory processes are predominantly orchestrated by the temporal lobe in conjunction with subcortical structures beneath the cerebral cortex, including the hippocampus and amygdala. The retention of memories necessitates the involvement of medial temporal lobe structures. HM's inability to forge new memories, now termed episodic memory, signified that he had retained short-term memory, which is evident in tasks like the three-word recall. However, the transient nature of these memories within a short span indicated their non-transfer to long-term storage due to the removal of the medial temporal lobe structures. The distinction between short-term, procedural, and episodic memory demonstrated through HM's case suggests that distinct cerebral regions govern these functions. The perpetual storage of episodic memory mandates the hippocampus and affiliated medial temporal structures, while the location of these memories resides in the multimodal integration zones of the cerebral cortex. In contrast, short-term memory—working or active memory—is localized to the prefrontal lobe. Notably, HM's loss of medial temporal lobes did not result in the forfeiture of existing memories, nor did it impede the formation of new short-term memories. Consequently, it was inferred that the role of the hippocampus and adjoining medial temporal lobe structures lies in the transference or consolidation of short-term memories (residing in the prefrontal lobe) to long-term memory (located in the temporal lobe).³⁹

Long-term potentiation (LTP) denotes a persistent augmentation in the synaptic efficacy between two neurons arising from synchronous stimulation. This phenomenon is postulated to play a pivotal role in memory encoding through synaptic strength modification, making LTP a fundamental cellular process underlying learning and memory.

For a visual depiction of LTP, a concise video is accessible at the link: http://www.youtube.com/watch?v=vso9jgfpI_c.

The hippocampus, a part of the limbic system, exhibits considerable plasticity, evident through LTP, as depicted in Figure 23. When subjected to high-frequency stimulation, the two axons that establish synapses with the pyramidal neurons within the hippocampus increase the amplitude of the EPSP, which is orchestrated through the following sequence: NMDA receptors, ordinarily obstructed by magnesium ion during neuronal inactivity, become unblocked upon depolarization. Glutamate, released by the presynaptic neuron, binds to AMPA receptors, inducing sodium ion influx and depolarization. This depolarization dislodges magnesium ions from the NMDA receptor, causing calcium ion influx, consequently triggering intracellular signaling pathways in the postsynaptic neuron. A resultant outcome of this signaling is the release of nitric oxide, which, in turn, prompts the presynaptic neuron to release additional glutamate and facilitates the insertion of more AMPA receptors. This sequence of heightened neurotransmitter release and increased receptor incorporation in a positive feedback manner constitutes a mechanism for establishing long-term memory in the hippocampus (Figure 24).⁴¹

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