Figure 8.

Experience driven synaptic insertion of GluR1 is required to permit stable spine enlargement in vivo. A, B, Two days of experience from P12 to P14 results in an increase in spine size. Spine size is defined as (integrated spine fluorescence)/(mean dendritic fluorescence). A, Cumulative distribution of spine size on cells expressing eGFP at P12 and P14. P12, n = 270 spines, 12 dendrites, 2 animals, median spine size, 41.3; P14, n = 374 spines, 12 dendrites, 2 animals, median spine size, 48.4. p < 0.01. B, Mean dendritic green fluorescence from cells in A. C–F, Expression of GluR1 mutants that block synaptic insertion prevent spine enlargement occurring from P12 to P14 resulting in smaller spines when compared with cells expressing wt GluR1. C, Cumulative distribution of spine size on cells expressing td-Tomato along with either SEP-GluR1 (wt) or (3A) at P14 for 2 d. wt, n = 436 spines, 21 dendrites, 2 animals, median spine size, 59.3; 3A, n = 695 spines, 29 dendrites, 2 animals, median spine size, 51.8; p < 0.02. D, Mean dendritic red fluorescence from cells in C, E, Cumulative distribution of spine size on cells expressing td-Tomato along with either SEP-GluR1 (wt) or (T887A) at P14 for 2 d. wt, n = 494 spines, 23 dendrites, 2 animals, median spine size, 75.2; T887A, n = 396 spines, 18 dendrites, 2 animals, median spine size, 51.5; p < 0.01. F, Mean dendritic red fluorescence from cells in E. G, Example images of red channel from cells expressing td-Tomato along with either SEP-GluR1 wt, 3A, or T887A. Spines are indicated by blue triangles. Error bars represent SEM. Scale bar, 1 μm. H, Model, LTP stimulus activates two pathways: one leading to a functional increase in synaptic strength through exocytosis and synaptic insertion of GluR1; the second leads to stable increase in spine size through actin remodeling. The synaptic incorporation of GluR1 and the increase of actin filaments in the spine costabilize one another, thus ensuring the balance between spine size and synapse strength is maintained. Solid arrows indicate “causes,” and dashed arrows indicate “stabilize.”