Effects of Antipsychotic Drugs and Potassium Channel Modulators on Cognition-related Local Field Potential Spectral Properties in Mouse Hippocampus and Frontal Cortex

Effects of Antipsychotic Drugs and Potassium Channel Modulators on Cognition-related Local Field Potential Spectral Properties in Mouse Hippocampus and Frontal Cortex

Publication date: May 25, 2020

Local field potentials (LFPs) recorded intracranially display a range of location specific oscillatory spectra which have been related to cognitive processes. Although the exact mechanisms producing LFPs are not completely understood, it is likely that voltage-gated ion channels which produce action potentials and patterned discharges play a significant role. It is also known that antipsychotic drugs (APDs) affect LFPs spectra and a direct inhibitory effect on voltage-gated potassium (K_v) channels has been reported. Additionally, K_v channels have been implicated in the pathophysiology of schizophrenia, a disorder for which APDs are primary therapies. In this study we sought to: i) better characterise the effects of two APDs on LFPs and connectivity measures and ii) examine the effects of potassium channel modulators on LFPs and potential overlap of effects with APDs. Intracranial electrodes were implanted in the hippocampus (HIP) and pre-frontal cortex (PFC) of C57BL/6 mice; power spectra, coherence and phase-amplitude cross frequency coupling were measured. Drugs tested were the APDs haloperidol and clozapine as well as voltage-gated potassium channel modulators (KVMs) 4-aminopyridine(4AP), tetraethylammonium (TEA), E-4031 and retigabine. All drugs and vehicle controls were administered intraperitoneally. Both APDs and KVMs significantly reduced gamma power with the exception of 4AP, which conversely increased slow-gamma power. Clozapine and retigabine additionally reduced coherence between HIP and PFC. Phase-amplitude coupling between theta and gamma oscillations in HIP was significantly reduced by the administration of haloperidol and retigabine. These results provide previously undescribed effects of APDs on LFP properties and demonstrate novel modulation of LFP characteristics by KVMs that intriguingly overlaps with the effects of APDs. The possibility of a common mechanism of action deserves further study.

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Concepts Keywords
Acetic Acid Aged weeks 26g
Action Potentials Dental cement
AEC Vehicle control solutions
Amplifier Epoch bandwidth product
Amplitude Acetic acid solution
Analgesic Psychotic illness
Antipsychotic Incision
Antipsychotic Drugs Implantation surgery
APDs Branches of biology
Bandpass Filter Electrophysiology
Betadine Retigabine
Brain Electroencephalography
CA1 Potassium channel
Cerebellum Channel modulator
CHN Action potential
Clozapine Neuroscience
Cognitive
Cohort
Connective Tissue
Coupling
Cross
Cyanoacrylate
Dimethyl Sulfoxide
DMSO
EEG
Electrode
Electronic Engineering
Ethanol
Faraday Cage
Frequency
Frontal Cortex
Functional Connectivity
Gamma Oscillations
Habituation
Haloperidol
Hippocampus
Hydrogen Peroxide
Hz
Implantation
Intraperitoneally
Isoflurane
LFP
Lucite
Melbourne
Mice
Modulation
Oxygen
Pathophysiology
Peritoneal
Potassium
Potassium Channels
Protocol
Psychosis
Psychotic Illness
Recording
Rectifier
Rodent
Royal Melbourne Hospital
Saline
Scalp
Schizophrenia
Sigma Aldrich
Silent
Skull
Spectra
Subcutaneously Injected
Synaptic
Tetraethylammonium
Tungsten
USB
Vivo
Voltage

Semantics

Type Source Name
drug DRUGBANK Potassium
disease MESH schizophrenia
drug DRUGBANK Tropicamide
drug DRUGBANK Haloperidol
drug DRUGBANK Clozapine
drug DRUGBANK Dalfampridine
drug DRUGBANK Tetraethylammonium
drug DRUGBANK Ezogabine
disease MESH psychosis
drug DRUGBANK Water
drug DRUGBANK Dimethyl sulfoxide
drug DRUGBANK Acetic acid
drug DRUGBANK Isoflurane
drug DRUGBANK Oxygen
drug DRUGBANK Carprofen
drug DRUGBANK Povidone-iodine
drug DRUGBANK Ethanol
drug DRUGBANK Hydrogen peroxide
drug DRUGBANK Pirenzepine
drug DRUGBANK Albendazole

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