title: Impairment of cognitive function by chemotherapy: association with the disruption of phase-locking and synchronization in anterior cingulate cortex.
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.
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong. limu22@cityu.edu.hk.|Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Kowloon, Hong Kong. limu22@cityu.edu.hk.
authors.forename: Li
authors.initials: L
authors.lastname: Mu
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong. juwang9-c@my.cityu.edu.hk.|Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Kowloon, Hong Kong. juwang9-c@my.cityu.edu.hk.|Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. juwang9-c@my.cityu.edu.hk.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong. bingcao1984@gmail.com.|Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Kowloon, Hong Kong. bingcao1984@gmail.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Cao
authors.affiliation: Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Kowloon, Hong Kong. Beth.Jelfs@cityu.edu.hk.|Department of Electronic Engineering, City University of Hong Kong, Kowloon, Hong Kong. Beth.Jelfs@cityu.edu.hk.
authors.forename: Beth
authors.initials: B
authors.lastname: Jelfs
authors.affiliation: Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Kowloon, Hong Kong. rosachan@cityu.edu.hk.|Department of Electronic Engineering, City University of Hong Kong, Kowloon, Hong Kong. rosachan@cityu.edu.hk.
authors.forename: Rosa H M
authors.initials: RH
authors.lastname: Chan
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong. xiaoxixu@cityu.edu.hk.|Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Kowloon, Hong Kong. xiaoxixu@cityu.edu.hk.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong. mhmshahed2@cityu.edu.hk.|Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Kowloon, Hong Kong. mhmshahed2@cityu.edu.hk.
authors.forename: Mahadi
authors.initials: M
authors.lastname: Hasan
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong. xuzhang1637@gmail.com.|Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Kowloon, Hong Kong. xuzhang1637@gmail.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong. yingli@cityu.edu.hk.|Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Kowloon, Hong Kong. yingli@cityu.edu.hk.|Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. yingli@cityu.edu.hk.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000503:physiopathology; D002945:Cisplatin / Q000009:adverse effects*; D003071:Cognition / Q000187:drug effects*; D003344:Cortical Synchronization / Q000187:drug effects*; D003657:Decision Making; D004358:Drug Therapy; D005106:Exploratory Behavior; D005715:Gambling; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects; D013826:Theta Rhythm / Q000187:drug effects
chemical_list: D002945:Cisplatin