Optogenetics and electron microscopy reveal an ultrafast mode of synaptic vesicle recycling, adding a new twist to a 40-year-old controversy

Optogenetics and electron microscopy reveal an ultrafast mode of synaptic vesicle recycling, adding a new twist to a 40-year-old controversy. - See more at: http://elifesciences.org/content/2/e01233#sthash.K8kQedyo.dpu

To the Question of Psychological Well-Being and Greed in a Person

The article examines the relationship between the idea of self-greed as a personality trait that contributes to the best results for themselves, at the expense of others, or by ignoring their needs, and psychological well-being, which is determined from the standpoint of eudemonistic approach. The survey method was used to determine the attitude of the subjects to their own well-being and greed; K. Riff's scale of psychological well-being (adaptation by T. Shevelenkova, P. Fesenko, 2005) to measure actual psychological well-being; methods of studying the semantic space of the concept of "greed" (Yanovska S., Lyutenko R., 2017), methods of statistical data processing. The sample (N = 141) aged 25 to 35 years, residents of Kharkiv, including 83 women and 58 men who had a job during the study, but 31 people worked part-time due to the coronavirus pandemic situation. It was determined that most of the subjects have an average level of psychological well-being and greed. Their ideas about psychological well-being are primarily related to health, material security, opportunities for self-development, independence and confidence in the future. Subjects are characterized as frugal, frugal people who understand moderation. They can share with others if it does not conflict with their own needs. The attitude to greed is ambiguous: most respondents consider greed a negative human trait, but there is also the opinion that greed is a motivating force of society. Significant links have been established between perceptions of one's own greed and a person's psychological well-being. A high level of greed reduces the number of trusting relationships, destroys interpersonal relationships and makes a person dependent. A person's moderate greed helps to increase his control over what is happening around him, creates the conditions and circumstances that are necessary to meet personal needs and achieve goals in problematic and uncertain conditions. The less a person uses others to meet his own needs, the greater his psychological well-being

Neurocalcin Delta Knockout Impairs Adult Neurogenesis Whereas Half Reduction Is Not Pathological

Neurocalcin delta (NCALD) is a brain-enriched neuronal calcium sensor and its reduction acts protective against spinal muscular atrophy (SMA). However, the physiological function of NCALD and implications of NCALD reduction are still elusive. Here, we analyzed the ubiquitous Ncald knockout in homozygous (NcaldKO/KO) and heterozygous (NcaldKO/WT) mice to unravel the physiological role of NCALD in the brain and to study whether 50% NCALD reduction is a safe option for SMA therapy. We found that NcaldKO/KO but not NcaldKO/WT mice exhibit significant changes in the hippocampal morphology, likely due to impaired generation and migration of newborn neurons in the dentate gyrus (DG). To understand the mechanism behind, we studied the NCALD interactome and identified mitogen-activated protein kinase kinase kinase 10 (MAP3K10) as a novel NCALD interacting partner. MAP3K10 is an upstream activating kinase of c-Jun N-terminal kinase (JNK), which regulates adult neurogenesis. Strikingly, the JNK activation was significantly upregulated in the NcaldKO/KO brains. Contrary, neither adult neurogenesis nor JNK activation were altered by heterozygous Ncald deletion. Taken together, our study identifies a novel link between NCALD and adult neurogenesis in the hippocampus, possibly via a MAP3K10-JNK pathway and emphasizes the safety of using NCALD reduction as a therapeutic option for SMA

Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1

Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure. Loss of Cadm1 protected mice from obesity, and tract-tracing analysis revealed Cadm1-positive innervation of POMC neurons via afferent projections originating from beyond the arcuate nucleus. Reducing Cadm1 expression in the hypothalamus and hippocampus promoted a negative energy balance and weight loss. These data identify essential roles for Cadm1-mediated neuronal input in weight regulation and provide insight into the central pathways contributing to human obesity.</p

Lysosomes convene to keep the synapse clean

In neurons, lysosomes regulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor levels at the plasma membrane, although their presence at distal dendrites is controversial. In this issue, Goo et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201704068) show for the first time that neuronal activity positions lysosomes at the dendritic spines to facilitate synaptic remodeling through local protein degradation

The tortoise and the hare revisited

Optogenetics and electron microscopy reveal an ultrafast mode of synaptic vesicle recycling, adding a new twist to a 40-year-old controversy. RESEARCH ORGANISM: C. elegan

Brain-specific functions of the endocytic machinery

Endocytosis is an essential cellular process required for multiple physiological functions, including communication with the extracellular environment, nutrient uptake, and signaling by the cell surface receptors. In a broad sense, endocytosis is accomplished through either constitutive or ligand-induced invagination of the plasma membrane, which results in the formation of the plasma membrane-retrieved endocytic vesicles, which can either be sent for degradation to the lysosomes or recycled back to the PM. This additional function of endocytosis in membrane retrieval has been adopted by excitable cells, such as neurons, for membrane equilibrium maintenance at synapses. The last two decades were especially productive with respect to the identification of brain-specific functions of the endocytic machinery, which additionally include but not limited to regulation of neuronal differentiation and migration, maintenance of neuron morphology and synaptic plasticity, and prevention of neurotoxic aggregates spreading. In this review, we highlight the current knowledge of brain-specific functions of endocytic machinery with a specific focus on three brain cell types, neuronal progenitor cells, neurons, and glial cells

Mechanisms of neuronal survival safeguarded by endocytosis and autophagy

Multiple aspects of neuronal physiology crucially depend on two cellular pathways, autophagy and endocytosis. During endocytosis, extracellular components either unbound or recognized by membrane-localized receptors (termed cargo) become internalized into plasma membrane-derived vesicles. These can serve to either recycle the material back to the plasma membrane or send it for degradation to lysosomes. Autophagy also uses lysosomes as a terminal degradation point, although instead of degrading the plasma membrane-derived cargo, autophagy eliminates detrimental cytosolic material and intracellular organelles, which are transported to lysosomes by means of double-membrane vesicles, referred to as autophagosomes. Neurons, like all non-neuronal cells, capitalize on autophagy and endocytosis to communicate with the environment and maintain protein and organelle homeostasis. Additionally, the highly polarized, post-mitotic nature of neurons made them adopt these two pathways for cell-specific functions. These include the maintenance of the synaptic vesicle pool in the pre-synaptic terminal and the long-distance transport of signaling molecules. Originally discovered independently from each other, it is now clear that autophagy and endocytosis are closely interconnected and share several common participating molecules. Considering the crucial role of autophagy and endocytosis in cell type-specific functions in neurons, it is not surprising that defects in both pathways have been linked to the pathology of numerous neurodegenerative diseases. In this review, we highlight the recent knowledge of the role of endocytosis and autophagy in neurons with a special focus on synaptic physiology and discuss how impairments in genes coding for autophagy and endocytosis proteins can cause neurodegeneration

Lysosomes convene to keep the synapse clean

In neurons, lysosomes regulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor levels at the plasma membrane, although their presence at distal dendrites is controversial. In this issue, Goo et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201704068) show for the first time that neuronal activity positions lysosomes at the dendritic spines to facilitate synaptic remodeling through local protein degradation

A population of descending tyraminergic/octopaminergic projection neurons of the insect deutocerebrum

In this study, we describe a cluster of tyraminergic/octopaminergic neurons in the lateral dorsal deutocerebrum of desert locusts (Schistocerca gregaria) with descending axons to the abdominal ganglia. In the locust, these neurons synthesize octopamine from tyramine stress-dependently. Electrophysiological recordings in locusts reveal that they respond to mechanosensory touch stimuli delivered to various parts of the body including the antennae. A similar cluster of tyraminergic/octopaminergic neurons was also identified in the American cockroach (Periplaneta americana) and the pink winged stick insect (Sipyloidea sipylus). It is suggested that these neurons release octopamine in the ventral nerve cord ganglia and, most likely, convey information on arousal and/or stressful stimuli to neuronal circuits thus contributing to the many actions of octopamine in the central nervous system