Kcns3-KO Mouse

Kcns3, encoding the Kv9.3 potassium channel α-subunit, is crucial for the function of voltage-gated potassium channels. These channels contribute to the precise detection of coincident excitatory synaptic inputs in parvalbumin (PV) neurons and are involved in the synchronization of cortical neural networks in γ-oscillations [2,3].

In Kcns3-deficient mice, Kcns3 mRNA levels were ~50% lower in cortical PV neurons compared to wild-type mice. Computational models and electrophysiology experiments showed that reduced Kv9.3 levels led to irregular spike trains, or stuttering, in PV basket cells (PVBCs), depressing their firing. Kcns3 deficiency also impaired the recruitment of PVBC firing at gamma frequency by stimuli mimicking synaptic input during cortical UP states, indicating that Kv9.3 subunits are critical for PVBC physiology [1].

In conclusion, Kcns3 is essential for the normal physiology of PV neurons, especially in maintaining the proper firing patterns and synchronization of cortical neural networks. The study of Kcns3-deficient mouse models has provided insights into the potential role of Kcns3 deficiency in schizophrenia, suggesting it could contribute to deficits in cortical gamma oscillations and cognitive impairments associated with the illness [1,2].

References:

1. Miyamae, Takeaki, Hashimoto, Takanori, Abraham, Monica, Lewis, David A, Gonzalez-Burgos, Guillermo. 2021. Kcns3 deficiency disrupts Parvalbumin neuron physiology in mouse prefrontal cortex: Implications for the pathophysiology of schizophrenia. In Neurobiology of disease, 155, 105382. doi:10.1016/j.nbd.2021.105382. https://pubmed.ncbi.nlm.nih.gov/33940180/

2. Georgiev, Danko, Arion, Dominique, Enwright, John F, Lewis, David A, Hashimoto, Takanori. . Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex in schizophrenia. In The American journal of psychiatry, 171, 62-71. doi:10.1176/appi.ajp.2013.13040468. https://pubmed.ncbi.nlm.nih.gov/24170294/

3. Georgiev, Danko, González-Burgos, Guillermo, Kikuchi, Mitsuru, Lewis, David A, Hashimoto, Takanori. 2012. Selective expression of KCNS3 potassium channel α-subunit in parvalbumin-containing GABA neurons in the human prefrontal cortex. In PloS one, 7, e43904. doi:10.1371/journal.pone.0043904. https://pubmed.ncbi.nlm.nih.gov/22937123/