Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking

Both episodic memory and executive function are impaired in amnestic mild cognitive impairment (aMCI) subjects, but it is unclear if these impairments are independent or interactive. The present study aimed to explore the relationship between episodic memory deficits and executive function deficits, and the underlying functional mechanisms in aMCI subjects. Thirty-one aMCI subjects and 27 healthy subjects underwent neuropsychological tests and multimodal magnetic resonance imaging (MRI) scans. Hippocampal networks and medial prefrontal cortex (MPFC) networks were identified based on resting-sate functional MRI (fMRI) data. AMCI subjects displayed lower episodic memory scores and executive function scores than control subjects, and the episodic memory scores were positively correlated with the executive function scores in aMCI subjects. Brain network analyses showed an interaction between the hippocampal networks and the MPFC networks, and the interaction was significantly associated with the episodic memory scores and the executive function scores. Notably, aMCI subjects displayed higher functional connectivity (FC) of the right hippocampal network with the right prefrontal cortex than did control subjects, but this difference disappeared when controlling for the MPFC networks. Furthermore, the effects of the MPFC networks on the hippocampal networks were significantly associated with the episodic memory scores in aMCI subjects. The present findings suggested that the episodic memory deficits in aMCI subjects could be partially underpinned by the modulation of the MPFC networks on the hippocampal networks.

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Encoding of the Intent to Drink Alcohol by the Prefrontal Cortex is blunted in Rats with a Family History of Excessive Drinking

10.1101/490664 ◽

2018 ◽

Cited By ~ 1

Author(s):

David N. Linsenbardt ◽

Nicholas M. Timme ◽

Christopher C. Lapish

Keyword(s):

Prefrontal Cortex ◽

Neural Activity ◽

Alcohol Drinking ◽

Wistar Rats ◽

Alcohol Intake ◽

Activity Patterns ◽

Excessive Drinking ◽

Lack Of Control ◽

History Of ◽

Excessive Alcohol

The prefrontal cortex plays a central role in guiding decision-making, and its function is altered by alcohol use and an individual’s innate risk for excessive alcohol drinking. The primary goal of this work was to determine how neural activity in the prefrontal cortex guides the decision to drink. Towards this goal, the within-session changes in neural activity were measured from medial prefrontal cortex (mPFC) of rats performing a drinking procedure that allowed them to consume or abstain from alcohol in a self-paced manner. Recordings were obtained from rats that either lacked or expressed an innate risk for excessive alcohol intake - Wistar or Alcohol Preferring ‘P’ rats, respectively. Wistar rats exhibited patterns of neural activity consistent with the intention to drink or abstain from drinking, whereas these patterns were blunted or absent in P rats. Collectively, these data indicate that neural activity patterns in mPFC associated with the intention to drink alcohol are influenced by innate risk for excessive alcohol drinking. This observation may indicate a lack of control over the decision to drink by this otherwise well-validated supervisory brain region.

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Enhancement of Oxytocin in the Medial Prefrontal Cortex Reverses Behavioral Deficits Induced by Repeated Ketamine Administration in Mice

Frontiers in Neuroscience ◽

10.3389/fnins.2021.723064 ◽

2021 ◽

Vol 15 ◽

Author(s):

Weili Zhu ◽

Zengbo Ding ◽

Zhihui Zhang ◽

Xiao Wu ◽

Xiaoya Liu ◽

...

Keyword(s):

Cognitive Impairment ◽

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Drugs Of Abuse ◽

Social Avoidance ◽

Behavioral Disturbances ◽

Behavioral Deficits ◽

Behavioral Abnormalities ◽

Tnf Α ◽

The Social

Ketamine is a popular recreational substance of abuse that induces persistent behavioral deficits. Although disrupted oxytocinergic systems have been considered to modulate vulnerability to developing drugs of abuse, the involvement of central oxytocin in behavioral abnormalities caused by chronic ketamine has remained largely unknown. Herein, we aimed to investigate the potential role of oxytocin in the medial prefrontal cortex (mPFC) in social avoidance and cognitive impairment resulting from repeated ketamine administration in mice. We found that ketamine injection (5 mg/kg, i.p.) for 10 days followed by a 6-day withdrawal period induced behavioral disturbances in social interaction and cognitive performance, as well as reduced oxytocin levels both at the periphery and in the mPFC. Repeated ketamine exposure also inhibited mPFC neuronal activity as measured by a decrease in c-fos-positive cells. Furthermore, direct microinjection of oxytocin into the mPFC reversed the social avoidance and cognitive impairment following chronic ketamine exposure. In addition, oxytocin administration normalized ketamine-induced inflammatory cytokines including TNF-α, IL-6, and IL-1β levels. Moreover, the activation of immune markers such as neutrophils and monocytes, by ketamine was restored in oxytocin-treated mice. Finally, the reversal effects of oxytocin on behavioral performance were blocked by pre-infusion of the oxytocin receptor antagonist atosiban into the mPFC. These results demonstrate that enhancing oxytocin signaling in the mPFC is a potential pathway to reverse social avoidance and cognitive impairment caused by ketamine, partly through inhibition of inflammatory stimulation.

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