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

Kim, Yujin; Hsu, Che-Hao; Cembrowski, Mark S.; Mensh, Brett D.; Spruston, Nelson

doi:10.7554/elife.06414

Cited by 87 publications

(127 citation statements)

References 132 publications

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“…Although these studies did not rigorously establish the unique role of NMDA spikes as in our experiments, they are consistent with our conclusion that dSpikes rather than bAPs provide the critical depolarization for LTP. Thus, NMDA spikes appear to be important for LTP at synapses in diverse brain regions, but other synapses have been shown to depend on other types of supralinear signalling8121314. It should be noted that in our preparation a single bAP almost never triggered an NMDA spike and did not induce LTP.…”

Section: Discussionmentioning

confidence: 60%

“…Previous work in diverse brain areas has shown that dendritic spikes generate the supralinear signal triggering plasticity at synapses where LTP can occur independently of bAPs56111213. Specifically for NMDAR-dependent dendritic spikes, in vivo investigations have provided correlative evidence for their role in synaptic plasticity in CA1 pyramidal cells41, in motor cortex10 and in barrel cortex11.…”

Section: Discussionmentioning

confidence: 99%

“…However, a number of observations have called into question the relevance of the bAP for LTP34. Importantly, LTP can be induced at various synapses in the absence of bAPs5678910111213. In these studies, regenerative dendritic events referred to as dendritic spikes (dSpikes) may produce the depolarization needed to trigger LTP.…”

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confidence: 99%

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Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells

et al. 2016

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The computational repertoire of neurons is enhanced by regenerative electrical signals initiated in dendrites. These events, referred to as dendritic spikes, can act as cell-intrinsic amplifiers of synaptic input. Among these signals, dendritic NMDA spikes are of interest in light of their correlation with synaptic LTP induction. Because it is not possible to block NMDA spikes pharmacologically while maintaining NMDA receptors available to initiate synaptic plasticity, it remains unclear whether NMDA spikes alone can trigger LTP. Here we use dendritic recordings and calcium imaging to analyse the role of NMDA spikes in associative LTP in CA3 pyramidal cells. We show that NMDA spikes produce regenerative branch-specific calcium transients. Decreasing the probability of NMDA spikes reduces LTP, whereas increasing their probability enhances LTP. NMDA spikes and LTP occur without back-propagating action potentials. However, action potentials can facilitate LTP induction by promoting NMDA spikes. Thus, NMDA spikes are necessary and sufficient to produce the critical postsynaptic depolarization required for associative LTP in CA3 pyramidal cells.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells

et al. 2016

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“…As a result of action potential firing and the subsequent neurotransmitter release, small, albeit significant calcium changes are seen in the dendrite and more specifically, the spines of neurons. There, the more subtle role of calcium in controlling encoding and dendritic excitability through local calcium transients is now becoming clear, and includes measures in behaving animals [90; 91; 92; 93; 94; 95; 96]. In field CA1, primary hippocampal neurons are able to integrate signals coming from distal inputs from the entorhinal cortex, and more proximal inputs emitting from area CA3.…”

Section: Cellular Calcium Transients Have a Dendritic Originmentioning

confidence: 99%

Calcium's role as nuanced modulator of cellular physiology in the brain

Frazier

Maimaiti

Anderson

et al. 2017

Biochemical and Biophysical Research Communications

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Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer’s disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration. Often the emphasis is on the negative impact of calcium dysregulation and the typical worse-case-scenario leading inevitably to cell death. However, even high amplitude calcium transients, when executed acutely can alter neuronal communication and synaptic strength in positive ways, without necessarily killing neurons. Here, we focus on the evidence that calcium has a subtle and distinctive role in shaping and controlling synaptic events that underpin neuronal communication and that these subtle changes in aging or AD may contribute to cognitive decline. We emphasize that calcium imaging in dendritic components is ultimately necessary to directly test for the presence of age- or disease-associated alterations during periods of synaptic activation.

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“…For instance, with the theta burst protocol for inducing LTP (Fig. 5A), proximal synaptic LTP requires pairing with backpropagating action potentials, but distal synapses recruit dendritic spikes and do not require backpropagating action potentials (Golding et al, 2002;Kim et al, 2015;Magee and Johnston, 1997).…”

Section: Degeneracy In Calcium Regulation and In The Induction Of Synmentioning

confidence: 99%

Degeneracy in hippocampal physiology and plasticity

Rathour

Narayanan

2017

Preprint

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Degeneracy, defined as the ability of structurally disparate elements to perform analogous function, has largely been assessed from the perspective of maintaining robustness of physiology or plasticity. How does the framework of degeneracy assimilate into an encoding system where the ability to change is an essential ingredient for storing new incoming information? Could degeneracy maintain the balance between the apparently contradictory goals of the need to change for encoding and the need to resist change towards maintaining homeostasis? In this review, we explore these fundamental questions with the mammalian hippocampus as an example encoding system. We systematically catalog lines of evidence, spanning multiple scales of analysis, that demonstrate the expression of degeneracy in hippocampal physiology and plasticity. We assess the potential of degeneracy as a framework to achieve encoding and homeostasis without cross-interferences, and postulate that multiscale parametric and interactional complexity could establish disparate routes towards accomplishing these conjoint goals. These disparate routes then provide several degrees of freedom to the encodinghomeostasis system in accomplishing its tasks in an input-and state-dependent manner. Finally, the expression of degeneracy spanning multiple scales offers an ideal reconciliation to several outstanding controversies, through the recognition that the seemingly contradictory disparate observations are merely alternate routes that the system might recruit towards accomplishment of its goals. Juxtaposed against the ubiquitous prevalence of degeneracy and its strong links to evolution, it is perhaps apt to add a corollary to Theodosius Dobzhansky's famous quote and state "nothing in physiology makes sense except in the light of degeneracy".peer-reviewed)

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

Cited by 87 publications

References 132 publications

Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells

Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells

Calcium's role as nuanced modulator of cellular physiology in the brain

Degeneracy in hippocampal physiology and plasticity

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