The Life Cycle of Ca2+ Ions in Dendritic Spines

Abstract

Spine Ca(2+) is critical for the induction of synaptic plasticity, but the factors that control Ca(2+) handling in dendritic spines under physiological conditions are largely unknown. We studied [Ca(2+)] signaling in dendritic spines of CA1 pyramidal neurons and find that spines are specialized structures with low endogenous Ca(2+) buffer capacity that allows large and extremely rapid [Ca(2+)] changes. Under physiological conditions, Ca(2+) diffusion across the spine neck is negligible, and the spine head functions as a separate compartment on long time scales, allowing localized Ca(2+) buildup during trains of synaptic stimuli. Furthermore, the kinetics of Ca(2+) sources governs the time course of [Ca(2+)] signals and may explain the selective activation of long-term synaptic potentiation (LTP) and long-term depression (LTD) by NMDA-R-mediated synaptic Ca(2+).

Complexity of calcium signaling in synaptic spines

“…Although Emptage and colleagues report that NMDAR-mediated release of Ca 2þ from stores underlies most of the Ca 2þ signal following single, subthreshold EPSPs, (83) this result has not been reproduced. (38,43,84) Moreover, our simulations, which quantitatively match Ca 2þ signaling profiles following an action potential, are able to account fully for the magnitude of the fluorescent Ca 2þ signal during an EPSP using conservative estimates of NMDAR numbers and single-channel Ca 2þ conductances, therefore suggesting that direct Ca 2þ influx through NMDARs is sufficient to account for the observed increase in intracellular Ca 2þ .…”

“…Recent reviews summarize the wealth of information that has been gleaned from these experiments. (46,47) In particular, Svoboda and colleagues (43,48,49) have provided much needed quantitative information about Ca 2þ dynamics in dendritic spines. The fundamental assumption underlying these experiments is that the spine can be treated as a single compartment.…”

“…a pre-before-post) results in a large increase in [Ca 2þ ] i which peaked at $10 mM, and decays at rates similar to the unpaired stimuli. (43) Can frequency-dependent plasticity and STDP be reconciled? LTP and LTD have been reliably induced with pre-before-post and post-before-pre pairings presented at frequencies as low as 0.133 Hz.…”

“…Induction of STDP is dependent on NMDAR and intracellular Ca 2þ , and partial blockade of NMDARs can induce LTD with a positively correlated pairing protocol. (23) In fact, pairings of pre-beforepost result in a superlinear increase in [Ca 2þ ] i (39)(40)(41)(42)(43) and postbefore-pre pairings result in a sublinear increase in [Ca 2þ ] i . (41) Thus, although the exact mechanisms remain unknown, it is likely that this form of synaptic plasticity shares many properties with the traditional, frequency-dependent forms of LTP and LTD. …”

Synaptogenesis and heritable aspects of executive attention

“…On the post-synaptic side, initiation of assembly involves the clustering of NMDA receptor subunits via PDZ-domains and interactions with the PSD-95 protein, a major component of the postsynaptic density. As NMDA channels are activated, both Ca ϩϩ and rho-familyGTPase dependent remodeling of the actin cytoskeleton and alterations in spine morphology (as seen in the time-lapse videos) facilitates further specialization of the post-synaptic density and optimal synaptic strength [Sabatini et al, 2002]. This core pathway of axonal contact, neurotransmitter release, assembly of the post-synaptic density, and spine morphogenesis is subject to many higher levels of feedback regulation.…”