» Articles » PMID: 31920555

Alterations of Electrophysiological Properties and Ion Channel Expression in Prefrontal Cortex of a Mouse Model of Schizophrenia

Overview
Specialty Cell Biology
Date 2020 Jan 11
PMID 31920555
Citations 7
Authors
Affiliations
Soon will be listed here.
Abstract

Maternal immune activation (MIA) and juvenile social isolation (SI) are two most prevalent and widely accepted environmental insults that could increase the propensity of psychiatric illnesses. Using a two-hit mouse model, we examined the impact of the combination of these two factors on animal behaviors, neuronal excitability and expressions of voltage-gated sodium (Nav) and small conductance calcium-activated potassium (SK) channels in the prefrontal cortex (PFC). We found that MIA-SI induced a number of schizophrenia-related behavioral deficits. Patch clamp recordings revealed alterations in electrophysiological properties of PFC layer-5 pyramidal cells, including hyperpolarized resting membrane potential (RMP), increased input resistance and enhanced medium after-hyperpolarization (mAHP). MIA-SI also increased the ratio of the maximal slope of somatodendritic potential to the peak slope of action potential upstroke, indicating a change in perisomatic Nav availability. Consistently, MIA-SI significantly increased the expression level of Nav1.2 and SK3 channels that contribute to the somatodendritic potential and the mAHP, respectively. Together, these changes may alter neuronal signaling in the PFC and behavioral states, representing a molecular imprint of environmental insults associated with neuropsychiatric illnesses.

Citing Articles

D-serine reconstitutes synaptic and intrinsic inhibitory control of pyramidal neurons in a neurodevelopmental mouse model for schizophrenia.

Zhang X, Xu L, Zhu X, Tang Z, Dong Y, Yu Z Nat Commun. 2023; 14(1):8255.

PMID: 38086803 PMC: 10716516. DOI: 10.1038/s41467-023-43930-8.


Contribution of Axon Initial Segment Structure and Channels to Brain Pathology.

Garrido J Cells. 2023; 12(8).

PMID: 37190119 PMC: 10137252. DOI: 10.3390/cells12081210.


Hyperoxygenation During Mid-Neurogenesis Accelerates Cortical Development in the Fetal Mouse Brain.

Markert F, Storch A Front Cell Dev Biol. 2022; 10:732682.

PMID: 35372333 PMC: 8969024. DOI: 10.3389/fcell.2022.732682.


Reduced expression of the psychiatric risk gene DLG2 (PSD93) impairs hippocampal synaptic integration and plasticity.

Griesius S, ODonnell C, Waldron S, Thomas K, Dwyer D, Wilkinson L Neuropsychopharmacology. 2022; 47(7):1367-1378.

PMID: 35115661 PMC: 9117295. DOI: 10.1038/s41386-022-01277-6.


Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.

Dwivedi D, Bhalla U Front Mol Neurosci. 2021; 14:658435.

PMID: 34149352 PMC: 8209339. DOI: 10.3389/fnmol.2021.658435.


References
1.
Jones C, Watson D, Fone K . Animal models of schizophrenia. Br J Pharmacol. 2011; 164(4):1162-94. PMC: 3229756. DOI: 10.1111/j.1476-5381.2011.01386.x. View

2.
Lukasz B, OSullivan N, Loscher J, Pickering M, Regan C, Murphy K . Peripubertal viral-like challenge and social isolation mediate overlapping but distinct effects on behaviour and brain interferon regulatory factor 7 expression in the adult Wistar rat. Brain Behav Immun. 2012; 27(1):71-9. DOI: 10.1016/j.bbi.2012.09.011. View

3.
Hashimoto H, Shintani N, Tanaka K, Mori W, Hirose M, Matsuda T . Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP). Proc Natl Acad Sci U S A. 2001; 98(23):13355-60. PMC: 60875. DOI: 10.1073/pnas.231094498. View

4.
Vukadinovic Z, Rosenzweig I . Abnormalities in thalamic neurophysiology in schizophrenia: could psychosis be a result of potassium channel dysfunction?. Neurosci Biobehav Rev. 2011; 36(2):960-8. DOI: 10.1016/j.neubiorev.2011.11.005. View

5.
Chen L, Huang J, Zhao P, Persson A, Dib-Hajj F, Cheng X . Conditional knockout of Na1.6 in adult mice ameliorates neuropathic pain. Sci Rep. 2018; 8(1):3845. PMC: 5832877. DOI: 10.1038/s41598-018-22216-w. View