Sexually dimorphic dopaminergic circuits determine sex preference.

Sociosexual preference is critical for reproduction and survival. However, neural mechanisms encoding social decisions on sex preference remain unclear. In this study, we show that both male and female mice exhibit female preference but shift to male preference when facing survival threats; their preference is mediated by the dimorphic changes in the excitability of ventral tegmental area dopaminergic (VTA) neurons.

Action Potential Firing Patterns Regulate Dopamine Release via Voltage-Sensitive Dopamine D2 Autoreceptors in Mouse Striatum In Vivo.

Dopamine (DA) in the striatum is vital for motor and cognitive behaviors. Midbrain dopaminergic neurons generate both tonic and phasic action potential (AP) firing patterns in behavior mice. Besides AP numbers, whether and how different AP firing patterns per se modulate DA release remain largely unknown.

STED Imaging of Vesicular Endocytosis in the Synapse.

Endocytosis is a fundamental biological process that couples exocytosis to maintain the homeostasis of the plasma membrane and sustained neurotransmission. Super-resolution microscopy enables optical imaging of exocytosis and endocytosis in live cells and makes an essential contribution to understanding molecular mechanisms of endocytosis in neuronal somata and other types of cells. However, visualization of exo-endocytic events at the single vesicular level in a synapse with optical imaging remains a great challenge to reveal mechanisms governing the synaptic exo-endocytotic coupling.

Zinc oxide nanoparticles damage the prefrontal lobe in mouse: Behavioral impacts and key mechanisms.

Zinc Oxide nanoparticles (ZnO NPs) have dualistic properties due to their advantage and toxicity. However, the impact and mechanisms of ZnO NPs on the prefrontal lobe have limited research. This study investigates the behavioral changes following exposure to ZnO NPs (34 mg/kg, 30 days), integrating multiple behaviors and bioinformatics analysis to identify critical factors and regulatory mechanisms.

An ACC-VTA-ACC positive-feedback loop mediates the persistence of neuropathic pain and emotional consequences.

The central mechanisms underlying pain chronicity remain elusive. Here, we identify a reciprocal neuronal circuit in mice between the anterior cingulate cortex (ACC) and the ventral tegmental area (VTA) that mediates mutual exacerbation between hyperalgesia and allodynia and their emotional consequences and, thereby, the chronicity of neuropathic pain. ACC glutamatergic neurons (ACC) projecting to the VTA indirectly inhibit dopaminergic neurons (VTA) by activating local GABAergic interneurons (VTA), and this effect is reinforced after nerve injury.

Single-cell RNA sequencing of murine hearts for studying the development of the cardiac conduction system.

The development of the cardiac conduction system (CCS) is essential for correct heart function. However, critical details on the cell types populating the CCS in the mammalian heart during the development remain to be resolved. Using single-cell RNA sequencing, we generated a large dataset of transcriptomes of ~0.

Synaptotagmin-1 is a bidirectional Ca sensor for neuronal endocytosis.

Exocytosis and endocytosis are tightly coupled. In addition to initiating exocytosis, Ca2+ plays critical roles in exocytosis–endocytosis coupling in neurons and nonneuronal cells. Both positive and negative roles of Ca2+ in endocytosis have been reported; however, Ca2+ inhibition in endocytosis remains debatable with unknown mechanisms.

Macrophage-mediated regulation of catecholamines in sympathetic neural remodeling after myocardial infarction.

Sympathetic neural remodeling, which involves the inflammatory response, plays an important role in ventricular arrhythmias (VAs) after myocardial infarction (MI). Adrenergic receptors on macrophages potentially modulate the inflammatory response. We hypothesized that the increased level of catecholamines activates macrophages and regulates sympathetic neural remodeling after MI.

Author Correction: Reversing a model of Parkinson's disease with in situ converted nigral neurons.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Reversing a model of Parkinson's disease with in situ converted nigral neurons.

Parkinson's disease is characterized by loss of dopamine neurons in the substantia nigra. Similar to other major neurodegenerative disorders, there are no disease-modifying treatments for Parkinson's disease. While most treatment strategies aim to prevent neuronal loss or protect vulnerable neuronal circuits, a potential alternative is to replace lost neurons to reconstruct disrupted circuits.

Synaptotagmins: Beyond Presynaptic Neurotransmitter Release.

Synaptotagmins (Syts) are well-established primary Ca sensors to initiate presynaptic neurotransmitter release. They also play critical roles in the docking, priming, and fusion steps of exocytosis, as well as the tightly coupled exo-endocytosis, in presynapses. A recent study by Awasthi and others (2019) shows that Syt3 Ca-dependently modulates the postsynaptic receptor endocytosis and thereby promotes the long-term depression (LTD) and the decay of long-term potentiation (LTP).

Differential Co-release of Two Neurotransmitters from a Vesicle Fusion Pore in Mammalian Adrenal Chromaffin Cells.

Co-release of multiple neurotransmitters from secretory vesicles is common in neurons and neuroendocrine cells. However, whether and how the transmitters co-released from a single vesicle are differentially regulated remains unknown. In matrix-containing dense-core vesicles (DCVs) in chromaffin cells, there are two modes of catecholamine (CA) release from a single DCV: quantal and sub-quantal.

α-Synuclein: A Multifunctional Player in Exocytosis, Endocytosis, and Vesicle Recycling.

α-synuclein (α-Syn) is a presynaptic enriched protein involved in the pathogenesis of Parkinson's disease. However, the physiological roles of α-Syn remain poorly understood. Recent studies have indicated a critical role of α-Syn in the sensing and generation of membrane curvature during vesicular exocytosis and endocytosis.

Intrastriatal transplantation of stem cells from human exfoliated deciduous teeth reduces motor defects in Parkinsonian rats.

Background: This study explored the neural differentiation and therapeutic effects of stem cells from human exfoliated deciduous teeth (SHED) in a rat model of Parkinson's disease (PD).

Methods: The SHED were isolated from fresh dental pulp and were induced to differentiate to neurons and dopamine neurons by inhibiting similar mothers against dpp (SMAD) signaling with Noggin and increase conversion of dopamine neurons from SHED with CHIR99021, Sonic Hedgehog (SHH) and FGF8 in vitro. The neural-primed SHED were transplanted to the striatum of 6-hydroxydopamine (6-OHDA)-induced PD rats to evaluate their neural differentiation and functions in vivo.

Synaptotagmin-11 is a critical mediator of parkin-linked neurotoxicity and Parkinson's disease-like pathology.

Loss-of-function mutations in Parkin are the most common causes of autosomal recessive Parkinson's disease (PD). Many putative substrates of parkin have been reported; their pathogenic roles, however, remain obscure due to poor characterization, particularly in vivo. Here, we show that synaptotagmin-11, encoded by a PD-risk gene SYT11, is a physiological substrate of parkin and plays critical roles in mediating parkin-linked neurotoxicity.

Molecular Mechanisms for the Coupling of Endocytosis to Exocytosis in Neurons.

Neuronal communication and brain function mainly depend on the fundamental biological events of neurotransmission, including the exocytosis of presynaptic vesicles (SVs) for neurotransmitter release and the subsequent endocytosis for SV retrieval. Neurotransmitters are released through the Ca- and SNARE-dependent fusion of SVs with the presynaptic plasma membrane. Following exocytosis, endocytosis occurs immediately to retrieve SV membrane and fusion machinery for local recycling and thus maintain the homeostasis of synaptic structure and sustained neurotransmission.

Striatal dopamine release in a schizophrenia mouse model measured by electrochemical amperometry in vivo.

Schizophrenia is a severely devastating mental disorder, the pathological process of which is proposed to be associated with the dysfunction of dopaminergic transmission. Our previous results have demonstrated slower kinetics of transmitter release (glutamate release in hippocampus and norepinephrine release in adrenal slice) in a schizophrenia model, dysbindin null-sandy mice. However, whether dopaminergic transmission in the nigrostriatal pathway contributes to the pathology of dysbindin-/- mice remains unknown.

Calcium influx activates adenylyl cyclase 8 for sustained insulin secretion in rat pancreatic beta cells.

Aims/hypothesis: Insulin is a key metabolic regulator in health and diabetes. In pancreatic beta cells, insulin release is regulated by the major second messengers Ca(2+) and cAMP: exocytosis is triggered by Ca(2+) and mediated by the cAMP/protein kinase A (PKA) signalling pathway. However, the causal link between these two processes in primary beta cells remains undefined.

Dopamine release from transplanted neural stem cells in Parkinsonian rat striatum in vivo.

Embryonic stem cell-based therapies exhibit great potential for the treatment of Parkinson's disease (PD) because they can significantly rescue PD-like behaviors. However, whether the transplanted cells themselves release dopamine in vivo remains elusive. We and others have recently induced human embryonic stem cells into primitive neural stem cells (pNSCs) that are self-renewable for massive/transplantable production and can efficiently differentiate into dopamine-like neurons (pNSC-DAn) in culture.

Extracellular Ca²⁺ per se inhibits quantal size of catecholamine release in adrenal slice chromaffin cells.

Classic calcium hypothesis states that depolarization-induced increase in intracellular Ca(2+) concentration ([Ca(2+)]i) triggers vesicle exocytosis by increasing vesicle release probability in neurons and neuroendocrine cells. The extracellular Ca(2+), in this calcium hypothesis, serves as a reservoir of Ca(2+) source. Recently we find that extracellular Ca(2+)per se inhibits the [Ca(2+)]i dependent vesicle exocytosis, but it remains unclear whether quantal size is regulated by extracellular, or intracellular Ca(2+) or both.

Temporal components of cholinergic terminal to dopaminergic terminal transmission in dorsal striatum slices of mice.

Striatal dopamine (DA) is critically involved in major brain functions such as motor control and deficits such as Parkinson's disease. DA is released following stimulation by two pathways: the nigrostriatal pathway and the cholinergic interneuron (ChI) pathway. The timing of synaptic transmission is critical in striatal circuits, because millisecond latency changes can reverse synaptic plasticity from long-term potentiation to long-term depression in a DA-dependent manner.