Hippocampus and LTD in Neurodegeneration

The hippocampus in the brain has long been established to play an important role in memory, including episodic memory in the brain. Episodic memory refers to the consolidation and memory of personal experiences.

Long-term depression (LTD) is defined as a lasting reduction of synaptic efficiency following stimulation in the hippocampus. Animals that have impaired long-term depression have also shown impairments in long-term fear memory. This has been demonstrated by an inability to complete the Morris Water Maze task, a behavioral task in which mice are provided a platform to swim within a small pool of water.1

In Alzheimer’s and other neurodegenerative diseases, long-term depression (LTD) and long-term potentiation (LTP) plays an important role. Weakening of the synapses occurs in LTD; LTD is crucial for synaptic plasticity. LTP increases the strengthening of synapses, resulting in an increase in strengthening of the synapses. LTP and LTD are opposing processes that work together to create neuroplasticity in different areas of the brain, including the hippocampus.

While LTD does play an important role, such as to clear old memories in the hippocampus, an increase in LTD at a high rate is harmful for cognitive function. It has been demonstrated that loss of synapses is one of the best indicators of disease progression in Alzheimer’s.2 Some experts suggest that AD is primarily a result of synaptic dysfunction. Excessive pruning of synapses can signal early neurodegeneration and can often be a predictor for neurodegenerative disease.

Amyloid-beta protein: PDB 1IYT. Rendered in PyMol.

Alpha-beta plaques are prominent in Alzheimer’s disease, these facilitate long-term depression. As alpha-beta plaques increase due to inflammation, long-term depression increases, leading to decreased signal transmission between neurons and more cognitive decline. 

References

1. Stacho, M., & Manahan-Vaughan, D. (2022). The intriguing contribution of hippocampal long-term depression to spatial learning and long-term memory. Frontiers in Behavioral Neuroscience, 16, 806356.

2. Koffie, R. M., Hyman, B. T., & Spires-Jones, T. L. (2011). Alzheimer's disease: synapses gone cold. Molecular neurodegeneration, 6, 1-9.