title: Altered intrinsic properties and bursting activities of neurons in layer IV of somatosensory cortex from Fmr-1 knockout mice.
abstract: Neuroadaptations and alterations in neuronal excitability are critical in brain maturation and many neurological diseases. Fragile X syndrome (FXS) is a pervasive neurodevelopmental disorder characterized by extensive synaptic and circuit dysfunction. It is still unclear about the alterations in intrinsic excitability of individual neurons and their link to hyperexcitable circuitry. In this study, whole cell patch-clamp recordings were employed to characterize the membrane and firing properties of layer IV cells in slices of the somatosensory cortex of Fmr-1 knockout (KO) mice. These cells generally exhibited a regular spiking (RS) pattern, while there were significant increases in the number of cells that adopted intrinsic bursting (IB) compared with age-matched wild type (WT) cells. The cells subgrouped according to their firing patterns and maturation differed significantly in membrane and discharge properties between KO and WT. The changes in the intrinsic properties were consistent with highly facilitated discharges in KO cells induced by current injection. Spontaneous activities of RS neurons driven by local network were also increased in the KO cells, especially in neonate groups. Under an epileptiform condition mimicked by omission of Mg(2+) in extracellular solution, these RS neurons from KO mice were more likely to switch to burst discharges. Analysis on bursts revealed that the KO cells tended to form burst discharges and even severe events manifested as seizure-like ictal discharges. These results suggest that alterations in intrinsic properties in individual neurons are involved in the abnormal excitability of cortical circuitry and possibly account for the pathogenesis of epilepsy in FXS.
authors.affiliation: Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China; Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Linming
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China.
authors.forename: Zhanrong
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Yi
authors.affiliation: Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Liao
authors.affiliation: Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. Electronic address: su@gzneurosci.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Su
mesh_terms: D000200:Action Potentials / Q000235:genetics / Q000502:physiology*; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D004558:Electric Stimulation; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D013003:Somatosensory Cortex / Q000166:cytology*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse
keywords: Epilepsy; Excitability; Firing pattern; Fragile X syndrome; Intrinsic membrane properties