The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic-pituitary-adrenal responses to stress

Background: Neuropathological features of Alzheimer’s disease are characterized by the deposition of amyloid-β (Aβ) plaques and impairments in synaptic activity and memory. However, we know little about the physiological role of amyloid-β protein precursor (AβPP) from which Aβ derives. Objective: Evaluate APP deficiency induced alterations in neuronal electrical activity and mitochondrial protein expression. Methods: Utilizing electrophysiological, biochemical, pharmacological, and behavioral tests, we revealed aberrant local field potential (LFP), extracellular neuronal firing and levels of mitochondrial proteins. Result: We show that APP knockout (APP -/- ) leads to increased gamma oscillations in the medial prefrontal cortex (mPFC) at 1-2 months old, which can be restored by baclofen (Bac), a γ-aminobutyric acid type B receptor (GABABR) agonist. A higher dose and longer exposure time is required for Bac to suppress neuronal firing in APP -/- mice than in wild type animals, indicating enhanced GABABR mediated activity in the mPFC of APP -/- mice. In line with increased GABABR function, the glutamine synthetase inhibitor, L-methionine sulfonate, significantly increases GABABR levels in the mPFC of APP -/- mice and this is associated with a significantly lower incidence of death. The results suggest that APP -/- mice developed stronger GABABR mediated inhibition. Using HEK 293 as an expression system, we uncover that AβPP functions to suppress GABABR expression. Furthermore, APP -/- mice show abnormal expression of several mitochondrial proteins. Conclusion: APP deficiency leads to both abnormal network activity involving defected GABABR and mitochondrial dysfunction, suggesting critical role of AβPP in synaptic and network function.

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The Role of the Medial Prefrontal Cortex in Moderating Neural Representations of Self and Other in Primates

Annual Review of Neuroscience ◽

10.1146/annurev-neuro-101420-011820 ◽

2021 ◽

Vol 44 (1) ◽

Author(s):

Masaki Isoda

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Critical Role ◽

Autism Spectrum ◽

Annual Review ◽

Publication Date ◽

Self And Other ◽

Neural Representations ◽

The Social

As a frontal node in the primate social brain, the medial prefrontal cortex (MPFC) plays a critical role in coordinating one's own behavior with respect to that of others. Current literature demonstrates that single neurons in the MPFC encode behavior-related variables such as intentions, actions, and rewards, specifically for self and other, and that the MPFC comes into play when reflecting upon oneself and others. The social moderator account of MPFC function can explain maladaptive social cognition in people with autism spectrum disorder, which tips the balance in favor of self-centered perspectives rather than taking into consideration the perspective of others. Several strands of evidence suggest a hypothesis that the MPFC represents different other mental models, depending on the context at hand, to better predict others’ emotions and behaviors. This hypothesis also accounts for aberrant MPFC activity in autistic individuals while they are mentalizing others. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Transcranial Magnetic Stimulation of the Medial Prefrontal Cortex Decreases Emotional Memory Schemas

Cerebral Cortex ◽

10.1093/cercor/bhz329 ◽

2020 ◽

Vol 30 (6) ◽

pp. 3608-3616 ◽

Cited By ~ 1

Author(s):

Leonore Bovy ◽

Ruud M W J Berkers ◽

Julia C M Pottkämper ◽

Rathiga Varatheeswaran ◽

Guillén Fernández ◽

...

Keyword(s):

Prefrontal Cortex ◽

Transcranial Magnetic Stimulation ◽

Medial Prefrontal Cortex ◽

Magnetic Stimulation ◽

Mood Induction ◽

Recognition Performance ◽

Memory Task ◽

Emotional Memory ◽

Memory Bias

Abstract Mood-congruent memory bias is a critical characteristic of depression, but the underlying neural mechanism is largely unknown. Negative memory schemas might enhance encoding and consolidation of negative experiences, thereby contributing to the genesis and perpetuation of depressive pathology. To investigate this relationship, we aimed to perturb medial prefrontal cortex (mPFC) processing, using neuronavigated transcranial magnetic stimulation (TMS) targeting the mPFC. Forty healthy volunteers first underwent a negative mood induction to activate negative schema processing after which they received either active inhibitory (N = 20) or control (N = 20) stimulation to the mPFC. Then, all participants performed the encoding of an emotional false memory task. Recall and recognition performance was tested the following morning. Polysomnographic data were recorded continuously during the night before and after encoding. We observed a significantly lower false recognition of negative critical lures following mPFC inhibition, but no differences in veridical memory. These findings were supported by reaction time data, showing a relative slower response to negative compared with positive critical lures. The current findings support previous causal evidence for a role of the mPFC in schema memory processing and further suggest a role of the mPFC in memory bias.

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