The Autism Related Protein Contactin-Associated Protein-Like 2 (CNTNAP2) Stabilizes New Spines: An In Vivo Mouse Study.

The establishment and maintenance of neuronal circuits depends on tight regulation of synaptic contacts. We hypothesized that CNTNAP2, a protein associated with autism, would play a key role in this process. Indeed, we found that new dendritic spines in mice lacking CNTNAP2 were formed at normal rates, but failed to stabilize. Notably, rates of spine elimination were unaltered, suggesting a specific role for CNTNAP2 in stabilizing new synaptic circuitry

Hotspots of dendritic spine turnover facilitate clustered spine addition and learning and memory.

Modeling studies suggest that clustered structural plasticity of dendritic spines is an efficient mechanism of information storage in cortical circuits. However, why new clustered spines occur in specific locations and how their formation relates to learning and memory (L&M) remain unclear. Using in vivo two-photon microscopy, we track spine dynamics in retrosplenial cortex before, during, and after two forms of episodic-like learning and find that spine turnover before learning predicts future L&M performance, as well as the localization and rates of spine clustering. Consistent with the idea that these measures are causally related, a genetic manipulation that enhances spine turnover also enhances both L&M and spine clustering. Biophysically inspired modeling suggests turnover increases clustering, network sparsity, and memory capacity. These results support a hotspot model where spine turnover is the driver for localization of clustered spine formation, which serves to modulate network function, thus influencing storage capacity and L&M

Correction: The Autism Related Protein Contactin-Associated Protein-Like 2 (CNTNAP2) Stabilizes New Spines: An In Vivo Mouse Study

The establishment and maintenance of neuronal circuits depends on tight regulation of synaptic contacts. We hypothesized that CNTNAP2, a protein associated with autism, would play a key role in this process. Indeed, we found that new dendritic spines in mice lacking CNTNAP2 were formed at normal rates, but failed to stabilize. Notably, rates of spine elimination were unaltered, suggesting a specific role for CNTNAP2 in stabilizing new synaptic circuitry

The Autism Related Protein Contactin-Associated Protein-Like 2 (CNTNAP2) Stabilizes New Spines: An In Vivo Mouse Study.

The establishment and maintenance of neuronal circuits depends on tight regulation of synaptic contacts. We hypothesized that CNTNAP2, a protein associated with autism, would play a key role in this process. Indeed, we found that new dendritic spines in mice lacking CNTNAP2 were formed at normal rates, but failed to stabilize. Notably, rates of spine elimination were unaltered, suggesting a specific role for CNTNAP2 in stabilizing new synaptic circuitry

Understanding the neurovascular unit at multiple scales: Advantages and limitations of multi-photon and functional ultrasound imaging

Developing efficient brain imaging technologies by combining a high spatiotemporal resolution and a large penetration depth is a key step for better understanding the neurovascular interface that emerges as a main pathway to neurodegeneration in many pathologies such as dementia. This review focuses on the advances in two complementary techniques: multi-photon laser scanning microscopy (MPLSM) and functional ultrasound imaging (fUSi). MPLSM has become the gold standard for in vivo imaging of cellular dynamics and morphology, together with cerebral blood flow. fUSi is an innovative imaging modality based on Doppler ultrasound, capable of recording vascular brain activity over large scales (i.e., tens of cubic millimeters) at unprecedented spatial and temporal resolution for such volumes (up to 10μm pixel size at 10kHz). By merging these two technologies, researchers may have access to a more detailed view of the various processes taking place at the neurovascular interface. MPLSM and fUSi are also good candidates for addressing the major challenge of real-time delivery, monitoring, and in vivo evaluation of drugs in neuronal tissue.status: publishe

Loss of Cntnap2-/- decreases spine density.

<p><b>a.</b> Low magnification images of dendrites and spines in WT mouse (<b>left)</b>, and in Cntnap2-/- mouse <b>(right)</b>. <b>b.</b> Quantification of spine-density. <b>Top plot</b> analysis per mouse (n = 10 Cntnap2-/- mice, n = 8 WT mice). <b>Bottom plot</b> analysis per cell (n = 23 Cntnap2-/- neurons, n = 18 WT neurons). Note the significant decrease in spine density in Cntnap2-/- mice (right) relative to WT (left).(Error bars indicate standard error (SEM), * P<0.05; **P<0.01; t-Test).</p

Loss of Cntnap2 decreases specifically stabilization of new spines.

<p><b>a.</b> From left to right: Chronic imaging through a cranial window of L5 pyramidal neuron. The 3 images on the right show the dynamics of spines on a dendrite segment followed for 11 days. <b>b-e. Top</b> a spine (red) on a dendrite (black) at the indicated imaging days. <b>Left plots</b> analysis per mouse (n = 10 Cntnap2-/- mice, n = 8 WT mice). <b>Right plots</b> analysis per cell (n = 23 Cntnap2-/- neurons, n = 18 WT neurons). <b>b.</b> The fraction of spines lost during 4 days. Note the significant increase in spine loss in Cntnap2-/- mice. <b>c.</b> The fraction of spines gain. Note the absence of a significant difference between WT and Cntnap2-/- animals. <b>d.</b> The fraction of maintained spines out of the spines which were stable during the first 4 days. Note the absence of a significant difference between WT and Cntnap2-/- animals. <b>e.</b> The fraction of stable spines out of the spines gained in the first 4 days. Note the significant decrease in Cntnap2-/- mice. (Error bars indicate standard error (SEM), NS non significant; * P<0.05; **P<0.01; t-Tests).</p

Hotspots of dendritic spine turnover facilitate clustered spine addition and learning and memory.

Modeling studies suggest that clustered structural plasticity of dendritic spines is an efficient mechanism of information storage in cortical circuits. However, why new clustered spines occur in specific locations and how their formation relates to learning and memory (L&amp;M) remain unclear. Using in vivo two-photon microscopy, we track spine dynamics in retrosplenial cortex before, during, and after two forms of episodic-like learning and find that spine turnover before learning predicts future L&amp;M performance, as well as the localization and rates of spine clustering. Consistent with the idea that these measures are causally related, a genetic manipulation that enhances spine turnover also enhances both L&amp;M and spine clustering. Biophysically inspired modeling suggests turnover increases clustering, network sparsity, and memory capacity. These results support a hotspot model where spine turnover is the driver for localization of clustered spine formation, which serves to modulate network function, thus influencing storage capacity and L&amp;M