IntroductionSchizophrenia is an incurable psychological disorder. It affects 1% of the population and accounts for a heavy healthcare burden worldwide. The current treatment paradigm has nearly 70% failure and is accompanied by severe side effects, indicating an unmet medical need that needs to be addressed. Reduced sleep spindles (cortical oscillations in the range of 8-16 Hz) have been robustly found not only in patients suffering from schizophrenia but also in their first-degree relatives. Since sleep spindles are generated from a neural circuit involving the cortical pyramidal neurons and the reticular thalamic nucleus (RTN) in the thalamus, it suggests that altered connectivity of thalamocortical pathways may be a predisposing factor contributing to the pathogenesis of schizophrenia. However, the involvement of connectivity between thalamic circuits and cortex in schizophrenia is largely unclear.Experimental MethodsStereotactic surgeryMice were anesthetized with isoflurane (3% induction, 1.5 % maintenance) and placed in a stereotaxic apparatus (David Kopf Instruments), and the height of Bregma and Lambda was adjusted to be within a difference of 0.1 mm. A warming pad maintained the core body temperature of mice. The EEG was recorded through four stainless steel screws implanted epidurally over the olfactory bulb (ground), frontal cortex (frontal EEG), parietal cortex (parietal EEG), and cerebellum (reference). The EMG was recorded through two stainless steel FEP-coated wires inserted bilaterally into the nuchal muscle. The electrodes were fixed to the skull using dental cement. For ablation of VM neurons, AAV10-CMV-CRE and AAV10-CMV-Flex-mCherry/DTA were microinjected into the VM (ML, ±0.88 mm; AP, -1.46 mm; DV, -4.21 mm) of C57BL/6J WT mice using a glass capillary and a syringe pump. For ablation of VMCalb1 neurons, AAV10-EF1α-DIO-EGFP, as well as AAV10-EF1α-flex-taCasp3-TEVp or AAV10-EF1α-mCherry, were microinjected. Trimethoprim (0.25 g/kg) was intraperitoneally injected for three consecutive days to maintain stable expression of Cre recombinase.Chih-Yao Liu2022. 4 ～ 2024. 5Masashi Yanagisawa, DirectorInternational Institute for Integrative Sleep Medicine, University of Tsukuba― 256 ―Elucidation of the neural mechanisms underlying schizophrenia towards therapeutics development
元のページ ../index.html#258