SYNAPTIC PLASTICITY Geometry of Calcium Signaling

Changes in intracellular calcium concentration ([Ca²⁺]_i) secondary to Ca²⁺ influx through N-methyl-D-aspartate type glutamate receptors (NMDARs) play a key role in long-term plastic changes in synaptic function that may be involved in learning and memory. Most excitatory synapses in the central nervous system are made onto dendritic spines, small protrusions of the dendritic shaft that enable changes in [Ca²⁺]_i to remain localized to individual synapses (see Hayashi and Majewski). Noguchi et al. used two-photon photolysis of caged glutamate combined with Ca²⁺ imaging and whole-cell patch clamp analysis to stimulate individual spines on neurons in rat hippocampal slices and investigate the effects of spine structure on Ca²⁺ signaling. NMDAR-dependent current increased with spine head volume; however, NMDAR-mediated increases in the [Ca²⁺]_i at the spine head were largest in small-volume spines, whereas increases in dendritic shaft [Ca²⁺]_i at the base of the spine were largest for large-volume spines. These differences in Ca²⁺ handling depended on the geometry of the spine neck: The necks of large spines allowed more rapid efflux of Ca²⁺ (and hence less compartmentation of spine-head [Ca²⁺]_i) than the necks of small spines. Measurement of current through NMDARs and -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid type receptors (AMPARs) indicated that, as spine size increased, the proportion of AMPAR-dependent current to NMDAR-dependent current increased. Thus, the authors suggest that the small spines may function as silent synapses and conclude that these differences in Ca²⁺ handling enable the preferential induction of long-term potentiation, which depends on changes in [Ca²⁺]_i, in smaller spines.

J. Noguchi, M. Matsuzaki, G. C. R. Ellis-Davies, H. Kasai, Spine-neck geometry determines NMDA receptor-dependent Ca²⁺ signaling in dendrites. Neuron 46, 609-622 (2005).[Online Journal]

Y. Hayashi, A. Majewski, Dendritic spine geometry: Functional implication and regulation. Neuron 46, 529-532 (2005). [Online Journal]