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

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

doi:10.1186/s13041-015-0125-y

Abstract

BackgroundPatients 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.ResultsIn 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.ConclusionsWe 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.

Highlights

The ‘chemobrain’ refers to a range of cognitive deficits caused by prolonged chemotherapy
We sought to characterize if chemotherapy disrupts long-term potentiation (LTP) in the amygdala-anterior cingulate cortex (ACC) network integrity, which is associated with mood disorder and deficits of learning and memory
Cisplatin suppressed spontaneous exploratory activity To examine if cisplatin-treated rats develop anxiety-like behavior we performed open field test (OFT)

Summary

Introduction

The ‘chemobrain’ refers to a range of cognitive deficits caused by prolonged chemotherapy. The anterior cingulated cortex (ACC) is a major cortical area of the limbic loop system, integrating emotion and cognition. The synaptic metaplasticity in the amygdala-ACC circuitry following prolonged chemotherapy has not been fully explored. We sought to characterize if chemotherapy disrupts LTP in the amygdala-ACC network integrity, which is associated with mood disorder and deficits of learning and memory. 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

Methods

Results

Conclusion