Impairment of cognitive function by chemotherapy: Association with the disruption of phase-locking and synchronization in anterior cingulate cortex

Li Mu, Jun Wang, Bing Cao, Beth Jelfs, Rosa H.M. Chan, Xiaoxiang Xu, Mahadi Hasan, Xu Zhang, Ying Li

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Background: Patients following prolonged cancer chemotherapy are at high risk of emotional and cognitive deficits. Research indicates that the brain neuronal temporal coding and synaptic long-term potentiation (LTP) are critical in memory and perception. We studied the effects of cisplatin on induction of LTP in the basolateral amygdala (BLA)-anterior cingulate cortex (ACC) pathway, characterized the coordination of spike timing with local theta oscillation, and identified synchrony in the BLA-ACC network integrity. Results: In the study presented, the impacts of cisplatin on emotional and cognitive functions were investigated by elevated plus-maze test, Morris water maze test, and rat Iowa gambling task (RGT). Electrophysiological recordings were conducted to study long-term potentiation. Simultaneous recordings from multi-electrodes were performed to characterize the neural spike firing and ongoing theta oscillation of local field potential (LFP), and to clarify the synchronization of large scale of theta oscillation in the BLA-ACC pathway. Cisplatin-treated rats demonstrated anxiety- like behavior, exhibited impaired spatial reference memory. RGT showed decrease of the percentage of good decision-makers, and increase in the percentage of maladaptive behavior (delay-good decision-makers plus poor decision-makers). Cisplatin suppressed the LTP, and disrupted the phase-locking of ACC single neural firings to the ongoing theta oscillation; further, cisplatin interrupted the synchrony in the BLA-ACC pathway. Conclusions: We provide the first direct evidence that the cisplatin interrupts theta-frequency phase-locking of ACC neurons. The block of LTP and disruption of synchronized theta oscillations in the BLA-ACC pathway are associated with emotional and cognitive deficits in rats, following cancer chemotherapy.

Original languageEnglish
Article number32
JournalMolecular Brain
Volume8
Issue number1
DOIs
Publication statusPublished - 23 May 2015
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Research Grants Council of Hong Kong [reference number: CityU 11100914, 160811, 160812, and 160713 to Y. Li; CityU 123312 to R. Chan], the National Science Foundation of China [81170353 to Y. Li], Health and Medical Research Fund of Hong Kong [reference number: CityU 01122006 to Y. Li] and City University of Hong Kong Neuroscience Research Infrastructure Grant [9610211 to Y. Li]. This work was also supported by the City University of Hong Kong Centre for Biosystems, Neuroscience, and Nanotechnology Grant [9360148 to S. Pang and Y. Li]. We thank Dr. Georges M. Halpern for editing manuscript.

Publisher Copyright:
© 2015 Mu et al.; licensee BioMed Central.

Keywords

  • Cisplatin
  • Decision-making
  • Learning and memory
  • Synaptic plasticity
  • Theta oscillation

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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