knockdown

The synaptic functions of Alpha Synuclein and Lrrk2

Alpha synuclein and Lrrk2 are key players in Parkinson's disease and related disorders, but their normal role has been confusing and controversial. Data from acute gene-editing based knockdown, followed by functional assays, will be presented.

NOTE: DUE TO A CYBER ATTACK OUR UNIVERSITY WEB SYSTEM IS SHUT DOWN - TALK WILL BE RESCHEDULED

The size and structure of the dendritic arbor play important roles in determining how synaptic inputs of neurons are converted to action potential output and how neurons are integrated in the surrounding neuronal network. Accordingly, neurons with aberrant morphology have been associated with neurological disorders. Dysmorphic, enlarged neurons are, for example, a hallmark of focal epileptogenic lesions like focal cortical dysplasia (FCDIIb) and gangliogliomas (GG). However, the regulatory mechanisms governing the development of dendrites are insufficiently understood. The evolutionary conserved Ste20/Hippo kinase pathway has been proposed to play an important role in regulating the formation and maintenance of dendritic architecture. A key element of this pathway, Ste20-like kinase (SLK), regulates cytoskeletal dynamics in non-neuronal cells and is strongly expressed throughout neuronal development. Nevertheless, its function in neurons is unknown. We found that during development of mouse cortical neurons, SLK has a surprisingly specific role for proper elaboration of higher, ≥ 3rd, order dendrites both in cultured neurons and living mice. Moreover, SLK is required to maintain excitation-inhibition balance. Specifically, SLK knockdown causes a selective loss of inhibitory synapses and functional inhibition after postnatal day 15, while excitatory neurotransmission is unaffected. This mechanism may be relevant for human disease, as dysmorphic neurons within human cortical malformations exhibit significant loss of SLK expression. To uncover the signaling cascades underlying the action of SLK, we combined phosphoproteomics, protein interaction screens and single cell RNA seq. Overall, our data identifies SLK as a key regulator of both dendritic complexity during development and of inhibitory synapse maintenance.

Locked nucleic acid antisense oligonucleotides: a new genetic tool to knockdown the gene encoding Nav1.7 in human induced-pluripotent stem cell-derived peripheral sensory neurons

Knockdown of Primary Ciliary Component Gene in Hypothalamic Paraventricular Nucleus Oxytocin Neurons Impairs Social Behavior

Microglia-specific knockdown of core clock gene Bmal1 leads to an altered behavioural phenotype and increased susceptibility to seizures in mice

Restoration of dopamine D2 receptors in the sensorimotor striatum of D2R knockdown mice selectively ameliorates deficits in motor skill learning

CRISPR-mediated approaches for ATXN2 knockdown in SCA2 models of disease

FENS Forum 2024

Knockdown of DMPK in myotonic dystrophy type 1 using Cas13

FENS Forum 2024

In vitro Rett syndrome model based on MeCP2 knockdown in iPSC-derived neurons

FENS Forum 2024