Skip to main content

Multifaceted Changes in Synaptic Composition and Astrocytic Involvement in a Mouse Model of Fragile X Syndrome.

Publication ,  Journal Article
Simhal, AK; Zuo, Y; Perez, MM; Madison, DV; Sapiro, G; Micheva, KD
Published in: Scientific reports
September 2019

Fragile X Syndrome (FXS), a common inheritable form of intellectual disability, is known to alter neocortical circuits. However, its impact on the diverse synapse types comprising these circuits, or on the involvement of astrocytes, is not well known. We used immunofluorescent array tomography to quantify different synaptic populations and their association with astrocytes in layers 1 through 4 of the adult somatosensory cortex of a FXS mouse model, the FMR1 knockout mouse. The collected multi-channel data contained approximately 1.6 million synapses which were analyzed using a probabilistic synapse detector. Our study reveals complex, synapse-type and layer specific changes in the neocortical circuitry of FMR1 knockout mice. We report an increase of small glutamatergic VGluT1 synapses in layer 4 accompanied by a decrease in large VGluT1 synapses in layers 1 and 4. VGluT2 synapses show a rather consistent decrease in density in layers 1 and 2/3. In all layers, we observe the loss of large inhibitory synapses. Lastly, astrocytic association of excitatory synapses decreases. The ability to dissect the circuit deficits by synapse type and astrocytic involvement will be crucial for understanding how these changes affect circuit function, and ultimately defining targets for therapeutic intervention.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Scientific reports

DOI

EISSN

2045-2322

ISSN

2045-2322

Publication Date

September 2019

Volume

9

Issue

1

Start / End Page

13855

Related Subject Headings

  • Vesicular Glutamate Transport Protein 2
  • Vesicular Glutamate Transport Protein 1
  • Tomography
  • Synapses
  • Somatosensory Cortex
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Magnetic Resonance Imaging
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Simhal, A. K., Zuo, Y., Perez, M. M., Madison, D. V., Sapiro, G., & Micheva, K. D. (2019). Multifaceted Changes in Synaptic Composition and Astrocytic Involvement in a Mouse Model of Fragile X Syndrome. Scientific Reports, 9(1), 13855. https://doi.org/10.1038/s41598-019-50240-x
Simhal, Anish K., Yi Zuo, Marc M. Perez, Daniel V. Madison, Guillermo Sapiro, and Kristina D. Micheva. “Multifaceted Changes in Synaptic Composition and Astrocytic Involvement in a Mouse Model of Fragile X Syndrome.Scientific Reports 9, no. 1 (September 2019): 13855. https://doi.org/10.1038/s41598-019-50240-x.
Simhal AK, Zuo Y, Perez MM, Madison DV, Sapiro G, Micheva KD. Multifaceted Changes in Synaptic Composition and Astrocytic Involvement in a Mouse Model of Fragile X Syndrome. Scientific reports. 2019 Sep;9(1):13855.
Simhal, Anish K., et al. “Multifaceted Changes in Synaptic Composition and Astrocytic Involvement in a Mouse Model of Fragile X Syndrome.Scientific Reports, vol. 9, no. 1, Sept. 2019, p. 13855. Epmc, doi:10.1038/s41598-019-50240-x.
Simhal AK, Zuo Y, Perez MM, Madison DV, Sapiro G, Micheva KD. Multifaceted Changes in Synaptic Composition and Astrocytic Involvement in a Mouse Model of Fragile X Syndrome. Scientific reports. 2019 Sep;9(1):13855.

Published In

Scientific reports

DOI

EISSN

2045-2322

ISSN

2045-2322

Publication Date

September 2019

Volume

9

Issue

1

Start / End Page

13855

Related Subject Headings

  • Vesicular Glutamate Transport Protein 2
  • Vesicular Glutamate Transport Protein 1
  • Tomography
  • Synapses
  • Somatosensory Cortex
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Magnetic Resonance Imaging