Tsuneya Ikezu
Oct 2, 2024; 44:e1170242024-e1170242024
Symposium

α-Neurexins are essential and highly expressed presynaptic cell-adhesion molecules that are frequently linked to neuropsychiatric and neurodevelopmental disorders. Despite their importance, how the elaborate extracellular sequences of α-neurexins contribute to synapse function is poorly understood. We recently characterized the presynaptic gain-of-function phenotype caused by a missense mutation in an evolutionarily conserved extracellular sequence of neurexin-3α (A687T) that we identified in a patient diagnosed with profound intellectual disability and epilepsy. The striking A687T gain-of-function mutation on neurexin-3α prompted us to systematically test using mutants whether the presynaptic gain-of-function phenotype is a consequence of the addition of side-chain bulk (i.e., A687V) or polar/hydrophilic properties (i.e., A687S). We used multidisciplinary approaches in mixed-sex primary hippocampal cultures to assess the impact of the neurexin-3α^A687 residue on synapse morphology, function and ligand binding. Unexpectedly, neither A687V nor A687S recapitulated the neurexin-3α A687T phenotype. Instead, distinct from A687T, molecular replacement with A687S significantly enhanced postsynaptic properties exclusively at excitatory synapses and selectively increased binding to neuroligin-1 and neuroligin-3 without changing binding to neuroligin-2 or LRRTM2. Importantly, we provide the first experimental evidence supporting the notion that the position A687 of neurexin-3α and the N-terminal sequences of neuroligins may contribute to the stability of α-neurexin–neuroligin-1 trans-synaptic interactions and that these interactions may specifically regulate the postsynaptic strength of excitatory synapses.

The brain's extracellular matrix (ECM) regulates neuronal plasticity and animal behavior. ECM staining shows a net-like structure around a subset of neurons, a ring-like structure at the nodes of Ranvier, and diffuse staining in the interstitial matrix. However, understanding the structural features of ECM deposition across various neuronal types and subcellular compartments remains limited. To visualize the organization pattern and assembly process of the hyaluronan-scaffolded ECM in the brain, we fused a HaloTag to hyaluronan proteoglycan link protein 1, which links hyaluronan and proteoglycans. Expression or application of the probe in primary rat neuronal cultures enables us to identify spatial and temporal regulation of ECM deposition and heterogeneity in ECM aggregation among neuronal populations. Dual-color birthdating shows the ECM assembly process in culture and in vivo. Sparse expression in mouse brains of either sex reveals detailed ECM architectures around excitatory neurons and developmentally regulated dendritic ECM. Our study uncovers extensive structural features of the brain's ECM, suggesting diverse roles in regulating neuronal plasticity.

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Hi,

I am looking to perform a net trace in a CDL file.

There is a net at a lower level and would like to know the net it is connected to at the top level.

Please let me know if there is a way to analyze the CDL file to perform this net trace.

Thanks,

Mallikarjun.

This blog explores how Virtuoso Studio Net Tracer can help you perform a design review.

We’ll use the net connectivity option, which allows the user to get a clean highlighted net. You can use the Net Tracer tool to highlight the nets. You can find the Net Tracer command under the connectivity pulldown menu in the layout window.

Trace manager and the ability to display different islands on the same net with other colors, you can identify and connect the unconnected islands as you wish.

The Net Tracer utility traces the nets in the physical view (layout). The trace is a highlighted net, which is a non-selectable object. The Net Tracer utility is available from Virtuoso Layout Suite XL onwards. You can use this utility based on your specific needs and preferences.

For a better understanding of the Net Tracer feature, let’s see one scenario between the circuit designer and layout engineer for a layout design review.

Circuit designer: Can we go through the routed input nets “inm” and “inp”?

Layout engineer: From the below layout view where they are highlighted using the XL connectivity, today I will use Net Tracer utility for the design review.

Circuit designer: I have never heard of this feature. Let's see how it works.

Layout engineer: Sure, now we turn on the Net Tracer toolbar using the below option.

You see the Net Tracer options form here:

As you can see on my screen, I have opened the layout view and engaged the Net Tracer utility.

Net Tracer allows shapes to be traced on a net in two tracing modes, namely, physical and logical, where shapes on the same net are physically or logically connected.

Physical tracing gathers all the shapes physically connected on the same net.

Logical tracing gathers all the shapes assigned to the same net. It highlights the net as in the source design (schematic). It will highlight shapes on the same net, even if they are isolated shapes that are not physically connected.

For this scenario, let us use physical tracing for input nets “inm” and “inp."

Highlighted nets are shown below:

Net “inm”                    Net “inp”                   Nets “inm” and “inp” 

Net Tracer has features like physical and logical tracing, preview, step-by-step mode, ease of tracing a net on a shape out of multiple underlying shapes, and so on.

Let us explore logical tracing for output nets “outm” and “outp”:

Here, you can see how to enable true color and halo before enabling logical tracing to identify the metal route. After enabling the true color halo, enable the logical trace.

Here, I am opening the trace manager to search “outm” and “outp” and click trace. That will trace the particular nets as shown.

Net Tracer has a preview feature, which is helpful in terms of the number of previewed objects. This preview capability hints at how the trace would appear when you create it. This useful feature in Virtuoso Studio highlights both completed and incomplete nets, helping the user better understand the status of the highlighted nets.

Circuit designer: Thanks for the design review. You have done good work. Net Tracer clearly shows both types of tracing, and it was even easy for the circuit designer to understand.

Layout engineer: Let me share the link to the Net Tracer RAK, where other layout engineers can explore many more amazing features of the Net Tracer.

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Sandhya.

On behalf of the Cadence Training team

Hello

i did a sp-Analysis and now i want to extract the maximum value of the s11 trace and the corresponding frequency.

I already tried ymax() in the calculator but i am suspecting it only works on transient Signals.

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Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.