scholarly journals Identification of the Hippocampal Input to Medial Prefrontal Cortex In Vitro

2009 ◽  
Vol 20 (2) ◽  
pp. 393-403 ◽  
Author(s):  
M. A. Parent ◽  
L. Wang ◽  
J. Su ◽  
T. Netoff ◽  
L.-L. Yuan
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex

scholarly journals Triumeq Increases Excitability of Pyramidal Neurons in the Medial Prefrontal Cortex by Facilitating Voltage-Gated Ca2+ Channel Function

2021 ◽  
Vol 11 ◽  
Author(s):  
Lihua Chen ◽  
Lena Al-Harthi ◽  
Xiu-Ti Hu
Keyword(s):  
Prefrontal Cortex ◽  
Side Effects ◽  
Medial Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Voltage Gated ◽  
Hiv Aids

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.

Multiple Forms of Short-Term Plasticity at Excitatory Synapses in Rat Medial Prefrontal Cortex

2000 ◽  
Vol 83 (5) ◽  
pp. 3031-3041 ◽  
Author(s):  
Chris M. Hempel ◽  
Kenichi H. Hartman ◽  
X.-J. Wang ◽  
Gina G. Turrigiano ◽  
Sacha B. Nelson
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Dynamic Properties ◽  
Specific Property ◽  
Pyramidal Cells ◽  
Excitatory Synapses ◽  
Short Term ◽  
Short Term Plasticity ◽  
Layer V

Short-term synaptic plasticity, in particular short-term depression and facilitation, strongly influences neuronal activity in cerebral cortical circuits. We investigated short-term plasticity at excitatory synapses onto layer V pyramidal cells in the rat medial prefrontal cortex, a region whose synaptic dynamic properties have not been systematically examined. Using intracellular and extracellular recordings of synaptic responses evoked by stimulation in layers II/III in vitro, we found that short-term depression and short-term facilitation are similar to those described previously in other regions of the cortex. In additition, synapses in the prefrontal cortex prominently express augmentation, a longer lasting form of short-term synaptic enhancement. This consists of a 40–60% enhancement of synaptic transmission which lasts seconds to minutes and which can be induced by stimulus trains of moderate duration and frequency. Synapses onto layer III neurons in the primary visual cortex express substantially less augmentation, indicating that this is a synapse-specific property. Intracellular recordings from connected pairs of layer V pyramidal cells in the prefrontal cortex suggest that augmentation is a property of individual synapses that does not require activation of multiple synaptic inputs or neuromodulatory fibers. We propose that synaptic augmentation could function to enhance the ability of a neuronal circuit to sustain persistent activity after a transient stimulus. This idea is explored using a computer simulation of a simplified recurrent cortical network.

Neuroprotective and anti-amnestic effects of a combination therapy in a model of photochemical ischemic damage in the prefrontal cortex

2018 ◽  
pp. 39-45
Author(s):  
Ф.М. Шакова ◽  
Т.И. Калинина ◽  
М.В. Гуляев ◽  
Г.А. Романова
Keyword(s):  
Prefrontal Cortex ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Combination Therapy ◽  
Neuroprotective Effect ◽  
Regulatory Protein ◽  
Human Growth ◽  
Neuroprotective Effects ◽  
Nerve Growth

Цель исследования - изучение влияния комбинированной терапии (мутантные молекулы эритропоэтина (EPO) и дипептидный миметик фактора роста нервов ГК-2H) на воспроизведение условного рефлекса пассивного избегания (УРПИ) и объем поражения коры мозга у крыс с двусторонним ишемическим повреждением префронтальной коры. Методика. Мутантные молекулы EPO (MЕРО-TR и MЕPО-Fc) с значительно редуцированной эритропоэтической и выраженной цитопротекторной активностью созданы методом генной инженерии. Используемый миметик фактора роста нервов человека, эндогенного регуляторного белка, в экспериментах in vitro проявлял отчетливые нейропротективные свойства. Двустороннюю фокальную ишемию префронтальной коры головного мозга крыс создавали методом фотохимического тромбоза. Выработку и оценку УРПИ проводили по стандартной методике. Объем повреждения мозга оценивался при помощи МРТ. MEPO-TR и MEPO-Fc (50 мкг/кг) вводили интраназально однократно через 1 ч после фототромбоза, ГК-2Н (1 мг/кг) - внутрибрюшинно через 4 ч после фототромбоза и далее в течение 4 послеоперационных суток. Результаты. Выявлено статистически значимое сохранение выработанного до ишемии УРПИ, а также значимое снижение объема повреждения коры при комплексной терапии. Полученные данные свидетельствуют об антиамнестическом и нейропротекторном эффектах примененной комбинированной терапии, которые наиболее отчетливо выражены в дозах: МEPO-Fc (50 мкг/кг) и ГК-2Н (1 мг/кг). Заключение. Подтвержден нейропротекторный эффект и усиление антиамнестического эффекта при сочетанном применении мутантных производных эритропоэтина - MEPO-TR и MEPO-Fc и дипептидного миметика фактора роста нервов человека ГК-2H. The aim of this study was to investigate the effect of combination therapy, including mutant erythropoietin molecules (EPO) and a dipeptide mimetic of the nerve growth factor, GK-2H, on the conditioned passive avoidance (PA) reflex and the volume of injury induced by bilateral ischemia of the prefrontal cortex in rats. Using the method of genetic engineering the mutant molecules of EPO, MERO-TR and MEPO-Fc, with strongly reduced erythropoietic and pronounced cytoprotective activity were created. The used human nerve growth factor mimetic, an endogenous regulatory protein based on the b-bend of loop 4, which is a dimeric substituted dipeptide of bis- (N-monosuccinyl-glycyl-lysine) hexamethylenediamine, GK-2 human (GK-2H), has proven neuroprotective in in vitro experiments. Methods. Bilateral focal ischemic infarction was modeled in the rat prefrontal cortex by photochemically induced thrombosis. The PA test was performed according to a standard method. Volume of brain injury was estimated using MRI. MEPO-TR, and MEPO-Fc (50 mg/kg, intranasally) were administered once, one hour after the injury. GK-2Н (1 mg/kg, i.p.) was injected four hours after the injury and then for next four days. Results. The study showed that the complex therapy provided statistically significant retention of the PA reflex developed prior to ischemia and a significant decrease in the volume of injury. The anti-amnestic and neuroprotective effects of combination therapy were most pronounced at doses of MEPO-Fc 50 mg/kg and GK-2H 1 mg/kg. Conclusion. This study has confirmed the neuroprotective effect and enhancement of the anti-amnestic effect exerted by the combination of mutant erythropoietin derivatives, MEPO-TR and MEPO-Fc, and the dipeptide mimetic of human growth factor GK-2H.

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