Parkinson’s Disease (PD) is a neurodegenerative disorder affecting the motor system. It is primarily due to substantial loss of midbrain dopamine (mDA) neurons in the substantia nigra pars compacta and to decreased innervation to the striatum. Although existing drug therapy available can relieve the symptoms in early-stage PD patients, it cannot reverse the pathogenic progression of PD. Thus, regenerating functional mDA neurons in PD patients may be a cure to the disease. The proof-of-principle clinical trials showed that human fetal graft-derived mDA neurons could restore the release of dopamine neurotransmitters, could reinnervate the striatum, and could alleviate clinical symptoms in PD patients. The invention of human-induced pluripotent stem cells (hiPSCs), autologous source of neural progenitors with less ethical consideration, and risk of graft rejection can now be generated in vitro. This advancement also prompts extensive research to decipher important developmental signaling in differentiation, which is key to successful in vitro production of functional mDA neurons and the enabler of mass manufacturing of the cells required for clinical applications. In this review, we summarize the biology and signaling involved in the development of mDA neurons and the current progress and methodology in driving efficient mDA neuron differentiation from pluripotent stem cells.

At present, the sparse representation-based classification (SRC) methods of electroencephalograph (EEG) signal analysis have become an important approach for studying brain science. SRC methods mean that the target data is sparsely represented on the basis of a fixed dictionary or learned dictionary, and classified based on the reconstruction criteria or the corresponding features extracted. SRC methods have been used to analyze the EEG signals of epilepsy, mild cognitive impairment (MCI) and Alzheimer's disease (AD) as well as brain computer interface (BCI), which yield some important achievements, including the improvement in computational accuracy, efficiency and robustness. However, when analyzing the EEG signals, these methods have deficiencies in real-time performance, generalization ability and the dependence of labeled sample. This paper analyzed the advantages and disadvantages of the SRC methods in the EEG signal analysis with the expectation that these methods can provide the better selection for analyzing EEG signals of preclinical mild cognitive impairment (Pre-MCI) patients.

γ oscillations are associated with higher brain functions such as memory, perception and consciousness. Disruption of γ oscillations occur in various neuro-psychological disorders such as schizophrenia. Nicotinic acetylcholine receptors (nAChR) are highly expressed in the hippocampus, however, little is known about the role on hippocampal persistent γ oscillation. This study examined the effects of nicotine and selective nAChR agonists and antagonists on kainate-induced persistent γ oscillation in rat hippocampal slices. Nicotine enhanced γ oscillation at concentrations of 0.1–10 μM, but reduced it at a higher concentration of 100 μM. The enhancement on γ oscillation can be best mimicked by co-application of α4β2- and α7- nAChR agonist and reduced by a combination of nAChR antagonists, DhβE and MLA. However, these nAChR antagonists failed to block the suppressing role of nicotine on γ. Furthermore, we found that the NMDA receptor antagonist D-AP5 completely blocked the effect of nicotine. These results demonstrate that nicotine modulates γ oscillations via α7 and α4β2 nAChR as well as NMDA activation, suggesting that nAChR activation may have a therapeutic role for the clinical disorder such as schizophrenia, which is known to have impaired γ oscillation and hypo-NMDA receptor function.

Near-death experiences (NDE) are episodes of enhanced perception with impending death, which have been associated with increased high-frequency (13–100 Hz) synchronization of neuronal activity, which is implicated in cognitive processes like perception, attention and memory. To test whether the NDE-associated high-frequency oscillations surge is related to cardiac arrest, recordings were made from the hippocampus of anesthetized rats dying from an overdose of the sedative chloral hydrate (CH). At a lethal dose, CH caused a surge in beta band power in CA3 and CA1 and a surge in gamma band power in CA1. CH increased the inter-regional coherence of high-frequency oscillations within and between hippocampi. Whereas the surge in beta power developed at non-lethal chloral hydrate doses, the surge in gamma power was specific for impending death. In contrast, CH strongly suppressed theta band power in both CA1 and CA3 and reduced inter-regional coherence in the theta band. The simultaneously recorded electrocardiogram showed a small decrease in heart rate but no change in waveform during the high-frequency oscillation surge, with cardiac arrest only developing after the cessation of breathing and collapse of all oscillatory activity. These results demonstrate that the high-frequency oscillation surge just before death is not limited to cardiac arrest and that especially the increase in gamma synchronization in CA1 may contribute to NDE observed both with and without cardiac arrest.

Hippocampal network oscillations at gamma band frequency (γ, 30-80 Hz) are closely associated with higher brain functions such as learning and memory. Acute ethanol exposure at intoxicating concentrations (≥50mM) impairs cognitive function. This study aimed to determine the effects and the mechanisms of acute ethanol exposure on γ oscillations in an in vitro model. Ethanol (25-100 mM) suppressed kainate-induced γ oscillations in CA3 area of the rat hippocampal slices, in a concentration-dependent, reversible manner. The ethanol-induced suppression was reduced by the D1R antagonist SCH23390 or the PKA inhibitor H89, was prevented by the Akt inhibitor Triciribine or the GSk3β inhibitor SB415286, was enhanced by the NMDA receptor antagonist D-AP5, but was not affected by the MAPK inhibitor U0126 or PI3K inhibitor wortmanin. Our results indicate the intracellular kinases Akt and GSk3β play a critical role in the ethanol-induced suppression of γ oscillations and reveal new cellular pathways involved in the ethanol-induced cognitive impairment.