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Brief Communications

SYNGAP1 Links the Maturation Rate of Excitatory Synapses to the Duration of Critical-Period Synaptic Plasticity

James P. Clement, Emin D. Ozkan, Massimiliano Aceti, Courtney A. Miller and Gavin Rumbaugh
Journal of Neuroscience 19 June 2013, 33 (25) 10447-10452; https://doi.org/10.1523/JNEUROSCI.0765-13.2013
James P. Clement
1Departments of Neuroscience and
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Emin D. Ozkan
1Departments of Neuroscience and
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Massimiliano Aceti
1Departments of Neuroscience and
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Courtney A. Miller
1Departments of Neuroscience and
2Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida 33458
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Gavin Rumbaugh
1Departments of Neuroscience and
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    Figure 1.

    syngap1 inactivation induces early maturation of TC synapses through a precocious accumulation of synaptic AMAPRs that directly restricts the duration of a critical-period plasticity window. A, Low-magnification image of TC fixed WT P9 slice showing the placement of stimulating electrode and recording electrode. B, Representative traces and summary data of A/N ratios evoked in VPM and patch clamp recorded in layer IV WT stellate cells at P4 (n = 6), P6 (n = 8), and P9 (n = 6). C, Same as B but in Het P4 [P4 (n = 6), P6 (n = 7), and P9 (n = 8)]. **p < 0.01 between genotypes; #p < 0.01 within genotypes (2-way ANOVA; Bonferroni's pairwise comparison). Arrows and dark gray bars indicate the time point at which measurement was obtained from all the experiments. D, Sequential measurement of isolated AMPAR-mediated (gray) and NMDAR-mediated (black) currents from neurons recorded in P5 TC slices (WT, n = 10; Het, n = 6). **p < 0.01, Student's t test. The A/N ratio was calculated for each cell by measuring the peak of each component at −70 mV. E, Representative recording and summary population data of LTPs evoked in VPM and perforated patch clamp recorded in layer IV stellate cells in P5 WT (n = 4) and Het (n = 4) animals. **p < 0.01, repeated-measures ANOVA. F, Same as E but in P8 (WT, n = 4; Het, n = 5). G, Top, An example recording of a minimal stimulation protocol designed to uncover silent synapses in TC slices derived from WT or Het mice at P5. Bottom, Summary of population data demonstrating a reduction in the number of silent synapses in P5 Het animals (WT, n = 4; Het = n = 4). ***p < 0.001, Student's t test. PND, Postnatal day.

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    Figure 2.

    syngap1 mutations accelerate GluN2A incorporation into developing TC synapses. A, Representative traces and summary data of GluN2B sensitivity to 3 μm ifenprodil recorded from layer IV stellate cells in P4–P5 WT and Het mice. B, Same as A but in P8–P9. **p < 0.01 within genotypes (wg) and #p < 0.01 between genotypes (2-way ANOVA, Bonferroni's pairwise comparison). Gray bar indicates the point at which measurement was obtained from all the cells. PND, Postnatal day.

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    Figure 3.

    Early excitatory synaptic maturation in mPFC layer II/III pyramidal neurons. A, A coronal section through the mouse brain illustrating the mPFC. Low-magnification image shows the prelimbic and cingulate cortices, in which recordings were obtained. High-magnification image (rotated 90° counterclockwise for clarity) shows an example of a layer II/III neuron. Cg1, Cingulate cortex area 1; PrL, prelimbic cortex; IL, infralimbic cortex. B, Representative traces and summary data of A/N ratios evoked locally and recorded in layer II/III pyramidal cells in P4–P15 WT. Calibration: 100 pA, 300 ms. C, Same as B but in Het mice. *p < 0.05 between genotypes; #,&p < 0.05 within genotypes [2-way ANOVA (data from B and C were included in analysis), Bonferroni's pairwise comparison]. Arrows and dark gray bars indicate the time point at which measurement was obtained from all the experiments. D, Golgi-stained mPFC layer II/III neurons from P8 WT or HET mice. Scale bar, 50 μm. E, Higher magnification of Golgi-stained neurons demonstrating a lack of spines present in both genotypes at this age. Scale bar, 10 μm. F, Adult WT mouse allows a frame of reference for Golgi-stained neurons and dendritic spine labeling. PND, Postnatal day.

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The Journal of Neuroscience: 33 (25)
Journal of Neuroscience
Vol. 33, Issue 25
19 Jun 2013
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SYNGAP1 Links the Maturation Rate of Excitatory Synapses to the Duration of Critical-Period Synaptic Plasticity
James P. Clement, Emin D. Ozkan, Massimiliano Aceti, Courtney A. Miller, Gavin Rumbaugh
Journal of Neuroscience 19 June 2013, 33 (25) 10447-10452; DOI: 10.1523/JNEUROSCI.0765-13.2013

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SYNGAP1 Links the Maturation Rate of Excitatory Synapses to the Duration of Critical-Period Synaptic Plasticity
James P. Clement, Emin D. Ozkan, Massimiliano Aceti, Courtney A. Miller, Gavin Rumbaugh
Journal of Neuroscience 19 June 2013, 33 (25) 10447-10452; DOI: 10.1523/JNEUROSCI.0765-13.2013
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