Entorhinal Cortex Inhibits Medial Prefrontal Cortex and Modulates the Activity States of Electrophysiologically Characterized Pyramidal Neurons In Vivo

Combination antiretroviral therapy (cART) suppresses HIV-1 replication, improves immune function, and prolongs the life of people living with HIV (PLWH). However, cART also induces neurotoxicity that could complicate HIV-induced neurodegeneration while reduce its therapeutic efficacy in treating HIV/AIDS. Triumeq is a first-line cART regimen, which is co-formulated by three antiretroviral drugs (ARVs), lamivudine (3TC), abcavir (ABC), and dolutegravir (DTG). Little is known about potential side effects of ARVs on the brain (including those co-formulating Triumeq), and their mechanisms impacting neuronal activity. We assessed acute (in vitro) and chronic (in vivo) effects of Triumeq and co-formulating ARVs on pyramidal neurons in rat brain slices containing the medial prefrontal cortex (mPFC) using patch-clamp recording approaches. We found that acute Triumeq or 3TC in vitro significantly increased firing of mPFC neurons in a concentration- and time-dependent manner. This neuronal hyperactivity was associated with enhanced Ca2+ influx through voltage-gated Ca2+ channels (VGCCs). Additionally, chronic treatment with Triumeq in vivo for 4 weeks (4 wks) also significantly increased firing and Ca2+ influx via VGCCs in mPFC neurons, which was not shown after 2 wks treatment. Such mPFC neuronal hyperexcitability was not found after 4 weeks treatments of individual ARVs. Further, chronic Triumeq exposure in vivo significantly enhanced mRNA expression of low voltage-activated (LVA) L-type Ca2+ channels (Cav1.3 L-channels), while changes in high voltage-activated (HVA) Cav1.2 L-channels were not observed. Collectively, these novel findings demonstrate that chronic cART induces hyperexcitability of mPFC pyramidal neurons by abnormally promoting VGCC overactivation/overexpression of VGCCs (including, but may not limited to, LVA-Cav1.3 L-channels), which could complicate HIV-induced neurotoxicity, and ultimately may contribute to HIV-associated neurocognitive disorders (HAND) in PLWH. Determining additional target(s) of cART in mPFC pyramidal neurons may help to improve the therapeutic strategies by minimizing the side effects of cART for treating HIV/AIDS.

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β1- and β2-Adrenergic activations enhance excitatory synaptic transmission in layer V/VI pyramidal neurons of the medial prefrontal cortex of rats

Neuroscience Research ◽

10.1016/j.neures.2010.07.1989 ◽

2010 ◽

Vol 68 ◽

pp. e449

Author(s):

Zejun Feng

Keyword(s):

Prefrontal Cortex ◽

Synaptic Transmission ◽

Medial Prefrontal Cortex ◽

Pyramidal Neurons ◽

Excitatory Synaptic Transmission ◽

Layer V

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In Vivo Effective Connectivity Between Mouse Ventral Hippocampal Projections and Medial Prefrontal Cortex Microcircuits

Biological Psychiatry ◽

10.1016/j.biopsych.2021.02.314 ◽

2021 ◽

Vol 89 (9) ◽

pp. S121-S122

Author(s):

David Kupferschmidt ◽

Thomas Clarity ◽

Rachel Mikofsky ◽

Kirsten Gilchrist ◽

Maxym Myroshnychenko ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Effective Connectivity

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D1 receptor antagonist-induced long-term depression in the medial prefrontal cortex of rat, in vivo: an animal model of psychiatric hypofrontality

Journal of Psychopharmacology ◽

10.1177/0269881108091256 ◽

2008 ◽

Vol 23 (6) ◽

pp. 672-685 ◽

Cited By ~ 7

Author(s):

RD Coppa-Hopman ◽

J Galle ◽

D Pimkine

Keyword(s):

Animal Model ◽

Prefrontal Cortex ◽

Receptor Antagonist ◽

Medial Prefrontal Cortex ◽

D1 Receptor ◽

Long Term Depression ◽

D1 Receptor Antagonist

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Novel Inferences in a Multidimensional Social Network Use a Grid-like Code

10.1101/2020.05.29.124651 ◽

2020 ◽

Author(s):

Seongmin A. Park ◽

Douglas S. Miller ◽

Erie D. Boorman

Keyword(s):

Decision Making ◽

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Entorhinal Cortex ◽

Brain Regions ◽

Cognitive Map ◽

General Mechanism ◽

Temporoparietal Junction ◽

Flexible Behavior ◽

Discrete Problems

ABSTRACTGeneralizing experiences to guide decision making in novel situations is a hallmark of flexible behavior. It has been hypothesized such flexibility depends on a cognitive map of an environment or task, but directly linking the two has proven elusive. Here, we find that discretely sampled abstract relationships between entities in an unseen two-dimensional (2-D) social hierarchy are reconstructed into a unitary 2-D cognitive map in the hippocampus and entorhinal cortex. We further show that humans utilize a grid-like code in several brain regions, including entorhinal cortex and medial prefrontal cortex, for inferred direct trajectories between entities in the reconstructed abstract space during discrete decisions. Moreover, these neural grid-like codes in the entorhinal cortex predict neural decision value computations in the medial prefrontal cortex and temporoparietal junction area during choice. Collectively, these findings show that grid-like codes are used by the human brain to infer novel solutions, even in abstract and discrete problems, and suggest a general mechanism underpinning flexible decision making and generalization.

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