NMDA receptor antagonist induced c-Fos expression in the medial entorhinal cortex during postnatal development.

IF 3 3区 医学 Q2 NEUROSCIENCES
Frontiers in Neural Circuits Pub Date : 2025-07-29 eCollection Date: 2025-01-01 DOI:10.3389/fncir.2025.1619534
Feng Liang, Hong Wang, Robert Konrad Naumann
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引用次数: 0

Abstract

N-methyl-D-aspartate receptor (NMDAR) antagonists, including ketamine, phencyclidine (PCP), and dizocilpine (MK-801), are an important class of drugs that can produce antidepressant, hallucinogenic, dissociative, psychotomimetic, and anesthetic effects in humans and animal models. To understand the effects of NMDAR antagonists on the brain, it is essential to map their actions at cellular resolution. We quantified c-Fos expressing cells in the mouse telencephalon after systemic injection of the potent NMDAR antagonist MK-801 and found a 10-fold higher density of c-Fos in the medial entorhinal cortex (MEC) compared to other regions of the telencephalon. c-Fos density was high in layer 3 of the dorsal MEC but low in other parts of the MEC. Since previous studies have shown that parvalbumin (PV) staining shows a strong dorsal-ventral gradient in the MEC, we investigated the spatial correlation between c-Fos and PV staining. We classified PV neurons based on their level of immunoreactivity and found that high and medium PV neurons were positively correlated with c-Fos density, while low PV neurons were negatively correlated. To understand the temporal correlation of c-Fos and PV staining, we examined their expression patterns after MK-801 injections during postnatal development. PV expression emerged on postnatal day 12, preceding c-Fos expression, which emerged on postnatal day 16. Our results suggest that local circuits comprising specific subtypes of inhibitory and excitatory neurons are critical for generating a sustained neuronal response to NMDAR antagonists. Furthermore, a high density of PV neuron input may be a prerequisite for the induction of c-Fos expression observed in MEC principal neurons. This study contributes to our understanding of how the brain responds to NMDAR antagonists in the developing and adult brain and reveals cell types in the dorsal MEC that are highly sensitive to this class of drugs.

NMDA受体拮抗剂诱导出生后发育过程中内嗅皮层c-Fos表达。
n -甲基- d -天冬氨酸受体(NMDAR)拮抗剂,包括氯胺酮、苯环利定(PCP)和二唑西平(MK-801),是一类重要的药物,可在人类和动物模型中产生抗抑郁、致幻、解离、拟精神和麻醉作用。为了了解NMDAR拮抗剂对大脑的影响,有必要在细胞分辨率上绘制它们的作用。我们在全身注射强效NMDAR拮抗剂MK-801后,对小鼠端脑中的c-Fos表达细胞进行了量化,发现内侧内嗅皮层(MEC)的c-Fos密度比端脑其他区域高10倍。c-Fos密度在背侧MEC第3层较高,而在MEC其他部位较低。由于先前的研究表明,小白蛋白(PV)染色在MEC中显示出强烈的背腹梯度,因此我们研究了c-Fos和PV染色之间的空间相关性。我们根据PV神经元的免疫反应性水平对其进行分类,发现高、中等PV神经元与c-Fos密度呈正相关,而低PV神经元与c-Fos密度呈负相关。为了了解c-Fos和PV染色的时间相关性,我们检测了在出生后发育过程中注射MK-801后c-Fos和PV染色的表达模式。PV在出生后第12天表达,c-Fos在出生后第16天表达。我们的研究结果表明,由特定亚型的抑制性和兴奋性神经元组成的局部回路对于产生对NMDAR拮抗剂的持续神经元反应至关重要。此外,PV神经元输入的高密度可能是在MEC主神经元中观察到的c-Fos表达诱导的先决条件。这项研究有助于我们理解大脑在发育和成人大脑中对NMDAR拮抗剂的反应,并揭示了对这类药物高度敏感的背侧MEC细胞类型。
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来源期刊
CiteScore
6.00
自引率
5.70%
发文量
135
审稿时长
4-8 weeks
期刊介绍: Frontiers in Neural Circuits publishes rigorously peer-reviewed research on the emergent properties of neural circuits - the elementary modules of the brain. Specialty Chief Editors Takao K. Hensch and Edward Ruthazer at Harvard University and McGill University respectively, are supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics and the public worldwide. Frontiers in Neural Circuits launched in 2011 with great success and remains a "central watering hole" for research in neural circuits, serving the community worldwide to share data, ideas and inspiration. Articles revealing the anatomy, physiology, development or function of any neural circuitry in any species (from sponges to humans) are welcome. Our common thread seeks the computational strategies used by different circuits to link their structure with function (perceptual, motor, or internal), the general rules by which they operate, and how their particular designs lead to the emergence of complex properties and behaviors. Submissions focused on synaptic, cellular and connectivity principles in neural microcircuits using multidisciplinary approaches, especially newer molecular, developmental and genetic tools, are encouraged. Studies with an evolutionary perspective to better understand how circuit design and capabilities evolved to produce progressively more complex properties and behaviors are especially welcome. The journal is further interested in research revealing how plasticity shapes the structural and functional architecture of neural circuits.
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