Research Lab

Circular RNAs in synaptic plasticity

Circular RNAs (circRNAs) are regulatory noncoding RNAs abundantly found in brain tissue. Their synaptically-enriched, activity-inducible, and developmentally-regulated properties suggest a role in experience-dependent synaptic plasticity. However, functional investigation of circRNAs in neurons is still in its infancy. Relatively little is known about their role in experience-dependent plasticity. Our work identified unique activity-dependent circRNAs upon plasticity induction. We found that circRNAs are robustly and differentially regulated. We demonstrated the changes of circRNAs in cortical and hippocampal synaptic plasticity. Our ongoing work will provide evidence of an experience-dependent circRNA that is a crucial regulator of synaptic development and plasticity as well as learning and memory.

Functional and molecular dissection of neurological disorders

Cortical visual impairment occurs in more than 75% of patients with CDKL5 deficiency disorder (CDD), a type of monogenic neurodevelopmental disorders. Although cortical visual impairment has been reported, how deficits in CDKL5 function leads to circuit-specific sensory processing impairment remain to be elucidated. Our ongoing work employs in vivo two-photon calcium imaging to examine how impaired neuronal activities in the primary visual cortex leads to circuit deficits. We also aim to identify the molecular mechanisms underlying cortical visual impairment. Through a phospho-proteomics screen, we identified novel substrates of CDKL5, which contains the CDKL5 phosphorylation consensus motif. Ongoing work aims to dissect the underlying molecular mechanism. All in all, our findings showed circuit-specific cortical impairment in CDD, and identified a novel mechanism mediated by CDKL5.

Corticohippocampal circuit in spatial learning and memory

The formation of memories requires the brain to encode, store, and retrieve information. This seemingly linear process involves different brain subregions to act in concert for memory formation. The hippocampus is located within the medial temporal lobe and serves crucial roles in spatial navigation and episodic memory. In particular, the dorsal CA1 (dCA1) is a key hippocampal subregion that encodes the organism’s location in space and time, and links specific behavioral events to the spatiotemporal framework. With the recent development of trans-synaptic tracing technology and whole-brain imaging, it is now possible to identify and examine novel or understudied circuitry. Therefore, we aim to identify novel or understudied brain regions that target the dCA1 and dissect their functional importance by performing cell-type-specific tracing in combination with in vivo miniscope imaging.

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2. Chai, Y., Lee, S.S.Y., Shillington, A., Du, X., Fok, C.K.M., Yeung, K.C., Siu, G.K.Y., Yuan, S., Zheng, Z., Tsang, H.W.S., Gu, S., Chen, Y., Ye, T. & Ip, J.P. (2023) Non-canonical C-terminal variant of MeCP2 R344W exhibits enhanced degradation rate. IBRO Neuroscience Reports. 22;15:218-224. doi: 10.1016/j.ibneur.2023.09.007.
3. El-Boustani, S.*, Ip, J.P.*, Breton-Provencher, V., Knott, G., Okuno, H., Bito, H., Sur, M. (2018) “Locally coordinated synaptic plasticity shapes cell-wide plasticity of visual cortex neurons in vivo” Science, Vol. 360, Issue 6395, pp. 1349-1354. *equal contribution
4. Ip, J.P., Mellios, N., Sur, M. (2018) “Rett Syndrome: genetic, molecular and functional insights into multi-stage dysfunction” Nature Review Neuroscience, Jun; 19(6): 368-382. Review.
5. Ip, J.P.*, Shi, L.*, Chen, Y., Itoh, Y., Fu, A. W., Betz, A., Yung, W. H., Gotoh, Y., Fu, A. K., Ip, N. Y. (2012) “α2-chimaerin controls neuronal migration and functioning of cerebral cortex through CRMP-2” Nature Neuroscience, (15) 39–47 (F1000 3 stars) *equal contribution