Abstract
Long-term potentiation (LTP), an increase in synaptic efficacy following high-frequency stimulation, is widely considered a mechanism of learning. LTP involves local remodeling of dendritic spines and synapses. Smooth endoplasmic reticulum (SER) and endosomal compartments could provide local stores of membrane and proteins, bypassing the distant Golgi apparatus. To test this hypothesis, effects of LTP were compared to control stimulation in rat hippocampal area CA1 at postnatal day 15 (P15). By two hours, small spines lacking SER increased after LTP, whereas large spines did not change in frequency, size, or SER content. Total SER volume decreased after LTP consistent with transfer of membrane to the added spines. Shaft SER remained more abundant in spiny than aspiny dendritic regions, apparently supporting the added spines. Recycling endosomes were elevated specifically in small spines after LTP. These findings suggest local secretory trafficking contributes to LTP-induced synaptogenesis and primes the new spines for future plasticity.
Highlights
As the longest and most architecturally complex cells in the body, neurons face the unique challenge of regulating membrane and protein levels in distal compartments
There was a significant increase in the field excitatory postsynaptic potential slope immediately after Theta burst stimulation (TBS) (Figure 1B,C)
These results provide several advances towards understanding mechanisms of enduring Long-term potentiation (LTP) in the developing hippocampus
Summary
As the longest and most architecturally complex cells in the body, neurons face the unique challenge of regulating membrane and protein levels in distal compartments. Synapses are often located hundreds of micrometers away from the neuronal cell body Adding to this spatial problem is the challenge of regulating protein abundance on the membrane in a temporally precise manner, as demanded by fast-acting processes such as synaptic potentiation. The Golgi apparatus is absent in most distal dendrites This puzzling observation has been resolved by recent work demonstrating that dendritic and somatic protein trafficking are highly segregated, and that glutamate receptors are trafficked through a specialized Golgi apparatus-independent pathway from the dendritic ER to the plasma membrane via recycling endosomes (Bowen et al, 2017). Long-term potentiation (LTP), the long-lasting enhancement of synaptic strength due to repetitive activity, is thought to underlie learning and memory This process has been studied extensively in the hippocampus, a key brain region responsible for new memory formation. The findings are consistent with the involvement of the Golgi-bypass secretory system in supporting synaptic plasticity in the developing hippocampus
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