Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons

Dendritic integration of synaptic inputs mediates rapid neural computation as well as longer-lasting plasticity. Several channel types can mediate dendritically initiated spikes (dSpikes), which may impact information processing and storage across multiple timescales; however, the roles of different channels in the rapid vs long-term effects of dSpikes are unknown. We show here that dSpikes mediated by Nav channels (blocked by a low concentration of TTX) are required for long-term potentiation (LTP) in the distal apical dendrites of hippocampal pyramidal neurons. Furthermore, imaging, simulations, and buffering experiments all support a model whereby fast Nav channel-mediated dSpikes (Na-dSpikes) contribute to LTP induction by promoting large, transient, localized increases in intracellular calcium concentration near the calcium-conducting pores of NMDAR and L-type Cav channels. Thus, in addition to contributing to rapid neural processing, Na-dSpikes are likely to contribute to memory formation via their role in long-lasting synaptic plasticity. DOI: http://dx.doi.org/10.7554/eLife.06414.001
eLife digest When we explore somewhere new, we activate a region of the brain that processes spatial information called the entorhinal cortex. This brain region stimulates the brain's memory-formation center, known as the hippocampus, which in turn forms a spatial memory of the new place. The process of forming these memories involves strengthening nerve connections, including those between the entorhinal cortex and the hippocampus. Groups of neurons that produce synchronized electrical activity will naturally strengthen the nerve connections between them. This led scientists to predict that synchronized electrical activity between neurons in the entorhinal cortex and the hippocampus may contribute to the formation of spatial memories. Previous research revealed that hippocampal neurons produced short bursts of electrical activity that are localized at specific sites along their branched nerve processes that extend out of the cell body and are where inputs from other neurons are received. These types of localized electrical activity have been associated with a strengthening of the nerve connections between the entorhinal cortex and the hippocampal neurons. Ion channels that allow calcium to flow through these neurons' cell membranes had been identified as a potential source of these local electrical activities, and calcium is responsible for the strengthening of nerve connections. But it remained unclear whether channels that allow only sodium ions to flow through might also be involved. Kim, Hsu et al. have now investigated this question by devising a way to selectively block the electrical activity produced by sodium ion channels on the branched nerve processes of hippocampal neurons. Slices of rat brain were collected and an inhibitor that specifically affected the sodium channels was delivered to the brain slices. Electrodes were used to stimulate the inputs from the entorhinal cortex, and to monitor the resulting electrical activity in the hippocampal neurons. Kim, Hsu et al. analyzed the results and reproduced them using computer simulations, which showed that sodium ion channels are essential for triggering brief electrical events within the individual branches of nerve processes. These local electrical events appeared to activate calcium channels to produce highly concentrated, short-lived calcium signals that are necessary for strengthening nerve connections. Future studies will determine whether local electrical activity mediated by sodium channels is also involved in strengthening nerve connections between other types of neurons, and how this mechanism affects the formation of memories. DOI: http://dx.doi.org/10.7554/eLife.06414.002