Investigating the regulation of a voltage-gated potassium channel in the cerebellum of a pharmacological mouse model of schizophrenia
Schizophrenia is a debilitating neurodevelopmental disorder affecting 1% of the global population. The glutamate hypothesis poses that the N-methyl-D-aspartate receptor (NMDAR) hypofunction is the key player in the development of different domains of schizophrenia symptoms. Phencyclidine (PCP) is a non-competitive NMDAR antagonist, which is widely used to generate animal models of schizophrenia1. The cerebellum has long been known for its motor related functions. Recently, an increasing body of evidence associates cerebellar structural and functional abnormalities with schizophrenia2. Voltage-gated potassium channels (Kv) play intricate roles in neuronal excitability and firing frequency. The Kv2.1 is a type of Kv which has been shown to regulate the excitability of neurons in the brain. Limited evidence suggests that the Kv2.1 gene is a schizophrenia vulnerability risk gene and the dysregulation of Kv2.1 in the brain is associated with schizophrenia3,4,5. This study aims to: 1) characterise the cellular and subcellular expression of Kv2.1 in the cerebellum; 2) investigate the regulation of Kv2.1 in a PCP mouse model of schizophrenia. Our preliminary data shows that Kv2.1 is expressed in the cerebellar Purkinje cells and granule cells and its expression is significantly downregulated in the cerebellum of the PCP mouse model (Figure 2).
Citation : Lagojda, L and Zhu, L.(2019) Investigating the regulation of a voltage-gated potassium channel in the cerebellum of a pharmacological mouse model of schizophrenia. BNA 2019 British Neuroscience Association , Festival of Neuroscience, Dublin, Ireland, April 2019.
Research Institute : Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)