Revisiting the flip side: Long-term depression of synaptic efficacy in the hippocampus

- Hippocampal long-term depression can be elicited using a variety of electrical and pharmacological stimulation both in vivo and in vitro.
- Intrinsic factors such as stress, sex hormones, neurotrophic factors, and age can affect the magnitude of LTD.
- Neurodevelopmental and neurodegenerative disorders can alter hippocampal LTD.

Synaptic plasticity is widely regarded as a putative biological substrate for learning and memory processes. While both decreases and increases in synaptic strength are seen as playing a role in learning and memory, long-term depression (LTD) of synaptic efficacy has received far less attention than its counterpart long-term potentiation (LTP). Never-the-less, LTD at synapses can play an important role in increasing computational flexibility in neural networks. In addition, like learning and memory processes, the magnitude of LTD can be modulated by factors that include stress and sex hormones, neurotrophic support, learning environments, and age. Examining how these factors modulate hippocampal LTD can provide the means to better elucidate the molecular underpinnings of learning and memory processes. This is in turn will enhance our appreciation of how both increases and decreases in synaptic plasticity can play a role in different neurodevelopmental and neurodegenerative conditions.