Consciousness loss during epileptogenesis: implication for VLPO-PnO circuits

Abstract

There is a growing concern about consciousness loss during epileptic seizures. Understanding neural mechanisms could lead to a better comprehension of cerebral circuit function in the control of consciousness loss in intractable epilepsy. We propose that ventrolateral preoptic area (VLPO)- PnO (nucleus pontis oralis) circuits may serve a major role in the loss of consciousness in drug-refractory epilepsy. Future behavioural and neuroimaging studies are clearly needed to understand the functional connectivity between the VLPO and PnO during loss of consciousness in drug-refractory epilepsy, to greatly prevent unconsciousness in this disorder and improve the quality of life in patients with intractable epilepsy.

Keywords: Consciousness loss; drug-refractory epilepsy; nucleus pontis oralis; ventrolateral preoptic area.

Figure 1

MC4R-GFP-positive neurons in the VLPO-PnO circuits. Injection of PRV-614 into the left kidney resulted in retrograde infection of neurons in the VLPO (A), NPO (B and C) by the sympathetic pathway. PRV-614/MC4R-GFP dual-labeled neurons were detected in the VLPO (A3) and NPO (C3). PRV-614/TH dual-labeled neurons were detected in the PPTg (B3). (A1, B1 and C1) show PRV-614-labeled cells; (A2 and C2) show MC4R-GFP-positive cells; (B2) shows TH-positive cells; and (A3, B3 and C3) show overlaid images of (A1, B1, and C1) plus (A2, B2, and C2), respectively. MC4R, melanocortin-4 receptor; PnO, pontine reticular formation; TH, tyrosine hydroxylase; VLPO, ventrolateral preoptic area. Arrows indicate double-labeled neurons. Scale bars, 50 μm. Some photomicrographs were taken from [28,29,42,43].

Figure 2

Schematic representation showing the VLPO-PnO circuits. This figure has been updated according to that reported in previous studies. Greee line: The Cre-dependent adeno-associated virus (AAV) encoding humanized Renilla green fluorescent protein was injected into the the nucleus accumbens in A2AR-Cre mice. Immunohistochemistry was then used to visualize hrGFP, highlighting the perikarya of the A2AR neurons in the injection sites, and their axons in projection regions, suggesting that VLPO neurons that project to the PnO were revealed by retrograde labeling. Red line: injection of PRV-614 into the kidney resulted in retrograde infection of neurons in the IML, PnO, and VLPO by the sympathetic pathway. PRV-614/MC4R-GFP duallabeled neurons were detected in the IML, PnO, and VLPO. IML, intermediolateral cell column. PnO, pontine reticular formation; VLPO, ventrolateral preoptic area. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article). Some drawings were taken from [14,28,29].