Abstract
The laying down of memory requires strong stimulation resulting in specific changes in synaptic strength and corresponding changes in size of dendritic spines. Strong stimuli can also be pathological, causing a homeostatic response, depressing and shrinking the synapse to prevent damage from too much Ca2+ influx. But do all types of dendritic spines serve both of these apparently opposite functions? Using confocal microscopy in organotypic slices from mice expressing green fluorescent protein in hippocampal neurones, the size of individual spines along sections of dendrite has been tracked in response to application of tetraethylammonium. This strong stimulus would be expected to cause both a protective homeostatic response and long-term potentiation. We report separation of these functions, with spines of different sizes reacting differently to the same strong stimulus. The immediate shrinkage of large spines suggests a homeostatic protective response during the period of potential danger. In CA1, long-lasting growth of small spines subsequently occurs consolidating long-term potentiation but only after the large spines return to their original size. In contrast, small spines do not change in dentate gyrus where potentiation does not occur. The separation in time of these changes allows clear functional differentiation of spines of different sizes.
Highlights
Dendritic spines form the postsynaptic element of most excitatory synapses in the mammalian cortex and hippocampus and their differing sizes and morphologies are directly related to synaptic strength [1]
Stretches of hippocampal dendrites were repeatedly scanned, reconstructed in 3D, and modelled (Figure 1(a)) at 10-minute intervals before (−10 min), during (0 min), and at several time points after (10, 20, 30, and 60 min) exposing the slice to tetraethylammonium chloride (TEA) or sorbitol or at the same time points with no change of solution
We studied spines both in the CA1 region where TEA causes long-term potentiation” (LTP) and in the dentate gyrus where LTP was absent under these conditions
Summary
Dendritic spines form the postsynaptic element of most excitatory synapses in the mammalian cortex and hippocampus and their differing sizes and morphologies are directly related to synaptic strength [1]. Being directly related to the strength of synapses, it is not surprising that the size of spines changes with plasticity of synaptic transmission [5,6,7] It remains controversial whether the diversity of spine morphologies represents a continuum, with size reflecting the history of the synapse or rather that spines with different morphological classifications represent different functional entities. Application of tetraethylammonium chloride (TEA) results in “chemical long-term potentiation” (LTP) at CA3-CA1 synapses [8] and has been shown to cause growth in a subset of small spines when imaged 2 hours after induction [9] Such global stimulation would be expected to cause an immediate protective homeostatic response due to both massive depolarisation and resulting glutamate release. In DG granule cells, where TEA does not cause long-term potentiation [10], the response of spines differs from that of CA1 pyramidal cells confirming the functional link between spine size and synaptic plasticity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
