1. (In)stability of spines

2. Outline Introduction Spine size and synaptic efficacy synaptic plasticity is associated with changes in number and size of spines Spontaneous changes in spine number and size Computational implications

3. What are spines? Cajal, 1888, Purkinje cell, Golgi staining

4. Morphology of spines Nimchinsky et al., 2002, hippocampal CA1 neuron, calcein imaged using 2-photon laser scanning microscopy (2PLSM)

5. 7μm7μm Morphology of spines Nimchinsky et al., 2002, hippocampal CA1 neuron, calcein imaged using 2-photon laser scanning microscopy (2PLSM)

6. Morphology of spines Nimchinsky et al., 2002, Purkinje cell

7. 5 μm Morphology of spines Nimchinsky et al., 2002, Purkinje cell

8. Diversity in spine shape McKinney, 2005, hippocampal CA1 neuron, GFP, 3d reconstruction

9. Spines and synapses >90% of excitatory synapses terminate on spines Neurotransmitter receptors are largely restricted to the surface of the spine

10. Kennedy, 2000 Spines and synapses

11. Harris, 1989 Correlation between spine volume and PSD area

12. Harris, 1989 Correlation between spine volume and vesicle number

13. Spine volume and synaptic efficacy Matsuzaki et al., 2001, 2-photon glutamate uncaging, Hippocampal CA1 neuron

14. Spine volume and synaptic efficacy

15. Spine number and synaptic plasticity Engert & Bonhoeffer, 1999, LTP (using local superfusion) is associated with an increase in the number of spines

17. Spine number and synaptic plasticity Engert & Bonhoeffer, 1999, LTP (using local superfusion) is associated with an increase in the number of spines

18. Spine size and synaptic plasticity Time-lapse images of dendritic spines on a hippocampal CA1 pyramidal neuron. The arrowhead indicates the spot of two-photon uncaging of MNI-glutamate, which was achieved by stimulation for 1 min at 1 Hz. b, Time course of spine-head volume, estimated from stacked images, of the stimulated (black circles) and neighbouring (green diamonds) spines shown in a. Matsuzaki et al., 2004, 1 μm

19. Spine size and synaptic plasticity Time-lapse images of a spine on a dendrite that was affected by electrical stimulation of presynaptic fibres at 2 Hz for 1 min; d, time course of the head volume. Matsuzaki et al., 2004,

20. Spine size and synaptic plasticity Averaged time courses of spine-head volume for two-photon uncaging of MNI-glutamate (circles), 2-Hz electrical stimulation in the absence of Mg2+ (blue open triangles) or 100 Hz electrical stimulation in the presence of Mg2+ (blue closed triangles). Matsuzaki et al., 2004,

21. Spine size and synaptic plasticity Time courses of spine-head volume (V, open symbols) and maximal AMPA currents (I, filled symbols) normalized to the original values. The data were derived from all the small spines that showed enlargement immediately after pairing stimulation. Circles and diamonds represent stimulated and neighbouring spines, respectively. Matsuzaki et al., 2004,

22. Are spines stable over time? (no) Trachtenberg et al., 2002, Pyramidal neuron, barrel cortex; Scale bar, 5 μm. 17% of spines are transient 23% of spines are semi-transient 60% of spines are stable

23. Even ‘stable’ spines are unstable Trachtenberg et al., 2002, Pyramidal neuron, barrel cortex; Scale bar, 5 μm. 15% of spines are disappear within 30 days

24. Sensory deprivation enhances spine turnover Trachtenberg et al., 2002, Pyramidal neuron, barrel cortex

25. Are spines stable over time? (yes) Grutzendler et al., 2002, Pyramidal neuron, visual cortex

26. Spine turnover decreases with animal age Grutzendler et al., 2002, Pyramidal neuron, visual cortex

27. Spine turnover depends on sensory input Holtmaat et al., 2006, Pyramidal neuron, barrel cortex

28. Are spines stable over time? Imaging results from Karel Svoboda’s lab indicate that the answer is ‘no’ Imaging results from Wen-Biao Gan’s lab indicate that the answer is ‘yes’ Some differences can be attributed to the cortical area and animal age. Two additional possible differences are: 1.Imaging approach: skull thinning (Gan) vs. no-skull window (Svoboda) 2. Data analysis: (are filopodia mistakenly considered as spines)

29. Is the size of stable spines stable over time? Holtmaat et al., 2005, spine volume and spine brightness are tightly correlated

30. Persistence of spines depends on their volume Holtmaat et al., 2005 persistent spines transient spines >1d

31. Persistence of spines depends on their volume Holtmaat et al., 2006, Pyramidal neuron, barrel cortex NPLPAP

32. Spine size changes over time The mean deviation (the average of the absolute values of all the deviations) from the mean percent change in spine head diameter increases progressively over time (solid circles). Both the mean (open squares) and mean deviation (open circles) of random change in spine head diameter (randomly pairing different spines between two views) remain relatively constant over different intervals. The mean deviation corresponding to randomly paired spines is comparable to the paired mean deviation over 18 months, suggesting that extensive changes in spine morphology occur during this period. Zuo et al., 2005, barrel cortex