Dataset Information

Compulsive-like Behaviors in Amyloid-β 1-42-Induced Alzheimer's Disease in Mice Are Associated With Hippocampo-cortical Neural Circuit Dysfunction.

ABSTRACT:

Background

In addition to memory deficits, patients with Alzheimer's disease (AD) experience neuropsychiatric disturbances. Recent studies have suggested the association of obsessive-compulsive disorder with the early stages of AD. However, there is a lack of understanding of the neurobiological underpinnings of compulsive-like behaviors at the neuronal circuit level and their relationship with AD.

Methods

We have addressed this issue in an amyloid-β 1-42-induced mouse model of AD by studying compulsive-like behaviors. Next, we compared the hippocampal and medial prefrontal cortex (mPFC) local field potential pattern and coherence between these regions of control and AD mice. We also assessed the expression pattern of acetylcholine and glutamatergic signaling in these regions, using quantitative polymerase chain reaction.

Results

Our findings show that AD mice exhibit compulsive-like behaviors, as evidenced by enhanced marble burying, nest building, and burrowing. Furthermore, AD mice exhibited hippocampo-cortical circuit dysfunction demonstrated by decreased power of rhythmic oscillations at the theta (4-12 Hz) and gamma (25-50 Hz) frequencies in the hippocampus and mPFC, two functionally interconnected brain regions involved both in AD and compulsive behaviors. Importantly, coherence between the hippocampus and mPFC in the theta band of AD animals was significantly reduced. Furthermore, we found reduced cholinergic and glutamatergic neurotransmission in the hippocampus and mPFC of AD mice.

Conclusions

We conclude that the hippocampo-cortical functional alterations may play a significant role in mediating the compulsive-like behaviors observed in AD mice. These findings may help in understanding the underlying circuit mechanisms of obsessive-compulsive disorder-like phenotypes associated with AD.

SUBMITTER: Shivakumar AB

PROVIDER: S-EPMC10593884 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Compulsive-like Behaviors in Amyloid-β 1-42-Induced Alzheimer's Disease in Mice Are Associated With Hippocampo-cortical Neural Circuit Dysfunction.

Shivakumar Apoorva Bettagere AB Kumari Sparsha S Mehak Sonam Fathima SF Gangadharan Gireesh G

Biological psychiatry global open science 20230307 4

<h4>Background</h4>In addition to memory deficits, patients with Alzheimer's disease (AD) experience neuropsychiatric disturbances. Recent studies have suggested the association of obsessive-compulsive disorder with the early stages of AD. However, there is a lack of understanding of the neurobiological underpinnings of compulsive-like behaviors at the neuronal circuit level and their relationship with AD.<h4>Methods</h4>We have addressed this issue in an amyloid-β 1-42-induced mouse model of AD ...[more]

PMID: 37881551

Similar Datasets

Project description:Emotional events are usually better remembered than neutral ones. This effect is mediated in part by a modulation of the hippocampus by the amygdala. Sleep plays a role in the consolidation of declarative memory. We examined the impact of sleep and lack of sleep on the consolidation of emotional (negative and positive) memories at the macroscopic systems level. Using functional MRI (fMRI), we compared the neural correlates of successful recollection by humans of emotional and neutral stimuli, 72 h after encoding, with or without total sleep deprivation during the first post-encoding night. In contrast to recollection of neutral and positive stimuli, which was deteriorated by sleep deprivation, similar recollection levels were achieved for negative stimuli in both groups. Successful recollection of emotional stimuli elicited larger responses in the hippocampus and various cortical areas, including the medial prefrontal cortex, in the sleep group than in the sleep deprived group. This effect was consistent across subjects for negative items but depended linearly on individual memory performance for positive items. In addition, the hippocampus and medial prefrontal cortex were functionally more connected during recollection of either negative or positive than neutral items, and more so in sleeping than in sleep-deprived subjects. In the sleep-deprived group, recollection of negative items elicited larger responses in the amygdala and an occipital area than in the sleep group. In contrast, no such difference in brain responses between groups was associated with recollection of positive stimuli. The results suggest that the emotional significance of memories influences their sleep-dependent systems-level consolidation. The recruitment of hippocampo-neocortical networks during recollection is enhanced after sleep and is hindered by sleep deprivation. After sleep deprivation, recollection of negative, potentially dangerous, memories recruits an alternate amygdalo-cortical network, which would keep track of emotional information despite sleep deprivation.

Dataset Information

Compulsive-like Behaviors in Amyloid-β 1-42-Induced Alzheimer's Disease in Mice Are Associated With Hippocampo-cortical Neural Circuit Dysfunction.

Background

Methods

Results

Conclusions

Publications

Compulsive-like Behaviors in Amyloid-β 1-42-Induced Alzheimer's Disease in Mice Are Associated With Hippocampo-cortical Neural Circuit Dysfunction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets