Loss-of-function variants in the human Zdhhc9 gene are identified in 2% of patients diagnosed with X-linked intellectual disability. These patients exhibit striking reductions in white matter volume and altered microstructure of white matter tracts. To further understand the role of Zdhhc9 in the brain and to elucidate how disrupting Zdhhc9 function contributes to phenotypes observed in patients, we have characterized a Zdhhc9 knockout mouse line. We demonstrate that Zdhhc9 is enriched in oligodendrocytes and is approximately two-fold higher in the corpus callosum than in any other region of the mouse brain. Zdhhc9 knockout mice exhibit significant reduction in myelin/oligodendrocyte associated markers, as well as reductions in the palmitoylation of these proteins, suggesting palmitoylation of myelin proteins may be required for their stability. RNA sequencing of different brain regions from control and Zdhhc9 knockout mice demonstrate differential expression of oligodendrocyte marker genes, suggesting a larger population of immature oligodendrocytes and fewer mature oligodendrocytes in knockout brains. This work provides a new perspective into the role of Zdhhc9 in oligodendrocytes and provides evidence that palmitoylation contributes to the development of white matter.

The role of palmitoylating enzyme, zDHHC9, in intellectual disability

The formation and remodeling of synaptic contacts require the precise distribution and trafficking of proteins to specialized compartments. This dynamic trafficking of synaptic proteins is partly controlled by S-palmitoylation, which is the most common form of post-translational lipid modification in the brain. Notably, several studies have shown that synaptic proteins can be differentially palmitoylated in response to synaptic activity. However, it is unclear how changes in synaptic activity alters protein palmitoylation. Here we show that increasing synaptic activity in primary rat hippocampal cultures using a well-established chemical LTP (cLTP) paradigm leads to post-translational modifications in ZDHHC enzymes which in turn impact enzyme stability, protein interaction and function. Notably, we observe the same post-translational modifications following the acquisition of contextual fear memory in vivo. In contrast to that observed for palmitoylating enzymes, we observed no activity-induced changes in the activity of thioesterases nor post-translational modifications of the thioesterase, ABHD17. These findings suggest that the differential palmitoylation of synaptic proteins following synaptic stimulation is mediated through post-translational modifications of ZDHHC enzymes that in turn regulate enzyme stability and function, and not through changes in depalmitoylating thioesterases.

Dynamic regulation of palmitoyltransferases by synaptic activity

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PS-2-C -  Disorders of the Nervous System

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Colleagues and Friends:

I am very happy to welcome you to the 14th annual Canadian Neuroscience Meeting, and to the first virtual edition of our meeting. I want to highlight the important work the CAN meeting chair, **Roger Thompson** and co-chair, **Alyson Fournier**, did to put together the great program we are offering this year. Moving to a virtual format required a complete re-design of the program, and both Roger and Alyson did a splendid job in providing us with an appealing and well adapted program for our first virtual event. I wish to thank them for this very important effort.

Highlights of this year’s scientific meeting include invited speakers **Michael Hausser, Franck Polleux, Gwyneth Card, Magdalena Götz**and Brain Prize winner **Huda Zoghbi**. Plenary and parallel symposia, proposed by our members complete our diverse [scientific program.](https://can-acn.org/meeting-2021/program-2021/)

The 2021 Advocacy session, chaired and organized by CAN advocacy committee chair **Karun Singh**, will feature a special lecture and question period with Member of Parliament and past Science Minister **Kirsty Duncan**. This will be followed by a short overview of CAN’s advocacy activities over the last year. We invite you to participate in this session for insight from Dr. Duncan on the workings of Parliament Hill, and to learn more about what CAN has been doing to promote neuroscience research in Canada.

We are also excited to host **Lisa Willis** in the Equity Diversity and Inclusion session, organized by EDI committee chair **Jibran Khokhar**.

A special highlight of our meeting will be the lectures by award-winning young neuroscientists. We are please to host the CAN 2020 Young Investigator Award winner **Mihaela Iordanova**, and CAN 2021 Young Investigator Award winners **Aaron Phillips** and **Tabrez Siddiqui**. Highlights will also include presentation by the top three winners of the CAN-CIHR-INMHA Brain Star Award winners, **Claire Gizowski, Nuria Daviu Abant** and **Lukas Tamayo-Orrego**.

Independently organized satellite symposia complement and complete this exciting program, check them out here: https://can-acn.org/meeting-2021/2021-satellite-symposia/

Some of the most engaging sessions are always the poster sessions featuring the work of our trainees, so make sure to log in to Gather Town during the poster sessions to chat with the presenters.
We hope you enjoy this program, and look forward to welcoming you, virtually.

Shernaz Bamji

President of the Canadian Association for Neuroscience

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Please head to https://can-acn.org/meeting-2021/registration-2021/ to register. 

CAN-ACN 2021

14th Canadian Neuroscience Meeting from August 23rd-25th

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Shernaz Bamji

4

SHORT BIO

Presentations

The role of palmitoylating enzyme, zDHHC9, in intellectual disability

Dynamic regulation of palmitoyltransferases by synaptic activity

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