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Trends in Neurosciences

Alessandra Perugini, Jochen Ditterich, Aasef G Shaikh, Barbara J Knowlton, Michele A Basso
People with Parkinson's disease (PD) show impaired decision-making when sensory and memory information must be combined. This recently identified impairment results from an inability to accumulate the proper amount of information needed to make a decision and appears to be independent of dopamine tone and reinforcement learning mechanisms. Although considerable work focuses on PD and decisions involving risk and reward, in this Opinion article we propose that the emerging findings in perceptual decision-making highlight the multisystem nature of PD, and that unraveling the neuronal circuits underlying perceptual decision-making impairment may help in understanding other cognitive impairments in people with PD...
May 7, 2018: Trends in Neurosciences
Erik Svensson, Michael J Williams, Helgi B Schiöth
Many neuronal circuits contain, or are influenced by, colocalized neurotransmitters, which are suggested to fine-tune circuit function. Much of our knowledge about cotransmission derives from studies in non-mammalian model systems, although a growing number of studies have provided insights into the physiological role of cotransmission in more complex mammalian circuits, including the spinal cord. Here we discuss the current picture of colocalized neurotransmitters in spinal circuits of non-mammalian and mammalian systems, as well as the progression towards understanding of their functional roles...
May 7, 2018: Trends in Neurosciences
Freek van Ede, Andrew J Quinn, Mark W Woolrich, Anna C Nobre
Frequency-specific patterns of neural activity are increasingly interpreted as transient bursts of isolated events rather than as rhythmically sustained oscillations. This has potentially far-reaching implications for theories of how such oscillations originate and how they shape neural computations. As this debate unfolds, we explore alternative interpretations and ask how best to distinguish between them.
May 5, 2018: Trends in Neurosciences
Suhan Senova, Antoine Chaillet, Andres M Lozano
Pharmacological neuromodulation strategies have shown limited efficacy in treating memory deficits related to Alzheimer's disease (AD). Despite encouraging results from a few preclinical studies, clinical trials investigating open-loop deep brain stimulation (DBS) for AD have not been successful. Recent refinements in understanding the various phases of memory processes, animal studies investigating phase-specific modulation of hippocampal activity during memorization, and clinical studies using closed-loop DBS strategies to treat patients with movement disorders, all point to the need to investigate closed-loop fornical DBS strategies to better understand memory dynamics and potentially treat memory deficits in AD preclinical models...
May 4, 2018: Trends in Neurosciences
Yeliz Yuva-Aydemir, Sandra Almeida, Fen-Biao Gao
GGGGCC (G4 C2 ) repeat expansion in C9ORF72 is the most common genetic cause of ALS and FTD. An important issue is how repeat RNAs and their translation products, various dipeptide repeat (DPR) proteins, cause neurodegeneration. Drosophila has been widely used to model G4 C2 repeat RNA and DPR protein toxicity. Overexpression of disease molecules in flies has revealed important molecular insights. These have been validated and further explored in human neurons differentiated from induced pluripotent stem cells (iPSCs), a disease-relevant model in which expanded G4 C2 repeats are expressed in their native molecular context...
May 2, 2018: Trends in Neurosciences
Stephan J Sanders, Arthur J Campbell, Jeffrey R Cottrell, Rikke S Moller, Florence F Wagner, Angie L Auldridge, Raphael A Bernier, William A Catterall, Wendy K Chung, James R Empfield, Alfred L George, Joerg F Hipp, Omar Khwaja, Evangelos Kiskinis, Dennis Lal, Dheeraj Malhotra, John J Millichap, Thomas S Otis, Steven Petrou, Geoffrey Pitt, Leah F Schust, Cora M Taylor, Jennifer Tjernagel, John E Spiro, Kevin J Bender
Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder, and intellectual disability. SCN2A encodes the neuronal sodium channel NaV 1.2. Functional assays demonstrate strong correlation between genotype and phenotype. This insight can help guide therapeutic decisions and raises the possibility that ligands that selectively enhance or diminish channel function may improve symptoms. The well-defined function of sodium channels makes SCN2A an important test case for investigating the neurobiology of neurodevelopmental disorders more generally...
April 22, 2018: Trends in Neurosciences
Albert K Lee, Michael Brecht
Intracellular recording allows measurement and perturbation of the membrane potential of identified neurons with sub-millisecond and sub-millivolt precision. This gives intracellular recordings a unique capacity to provide rich information about individual cells (e.g., high-resolution characterization of inputs, outputs, excitability, and structure). Hence, such recordings can elucidate the mechanisms that underlie fundamental phenomena, such as brain state, sparse coding, gating, gain modulation, and learning...
April 20, 2018: Trends in Neurosciences
Eva K Fischer, Lauren A O'Connell
Parental care is a key evolutionary innovation that influences the fitness of parents and offspring. How the brain coordinates such a complex behavior remains poorly understood. Kohl and colleagues recently uncovered the organizational principles of hypothalamic galanin neurons and their connections in mice. Their findings revealed a striking picture in which discrete neuronal pools control distinct aspects of parental behavior.
April 20, 2018: Trends in Neurosciences
Kristine A Wilckens, Fabio Ferrarelli, Matthew P Walker, Daniel J Buysse
Slow-wave activity (SWA), and its coupling with other sleep features, reorganizes cortical circuitry, supporting cognition. This raises the question: can cognition be improved through SWA enhancement? SWA enhancement techniques range from behavioral interventions (such as exercise), which have high feasibility but low specificity, to laboratory-based techniques (such as transcranial stimulation), which have high specificity but are less feasible for widespread use. In this review we describe the pathways through which SWA is enhanced...
April 5, 2018: Trends in Neurosciences
Tetsuji Sekiya, Matthew C Holley
Cell transplantation is an ambitious, but arguably realistic, therapy for repair of the nervous system. Cell delivery is a major challenge for clinical translation, especially given the apparently inhibitory astrogliotic environment in degenerated tissue. However, astrogliotic tissue also contains endogenous structural and biochemical cues that can be harnessed for functional repair. Minimizing damage to these cues during cell delivery could enhance cell integration. This theory is supported by studies with an auditory astrocyte scar model, in which cells delivered onto the surface of the damaged nerve were more successfully integrated in the host than those injected into the tissue...
April 3, 2018: Trends in Neurosciences
Liam G Coulthard, Owen A Hawksworth, Trent M Woodruff
Complement activation products have long been associated with roles in the innate immune system, linking the humoral and cellular responses. However, among their recently described non-inflammatory roles, complement proteins also have multiple emerging novel functions in brain development. Within this context, separate proteins and pathways of complement have carved out physiological niches in the formation, development, and refinement of neurons. They demonstrate actions that are both reminiscent of peripheral immune actions and removed from them...
March 29, 2018: Trends in Neurosciences
Mea M Holm, Julia Kaiser, Martin E Schwab
The physiology of the central nervous system (CNS) is built on a foundation of connection, integration, and the exchange of complex information among brain cells. Emerging evidence indicates that extracellular vesicles (EVs) are key players in the intercellular communication that underlies physiological processes such as synaptic plasticity and the maintenance of myelination. Furthermore, upon injury to the CNS, EVs may propagate inflammation across the blood-brain barrier and beyond, and also appear to mediate neuroprotection and modulate regenerative processes...
March 28, 2018: Trends in Neurosciences
Karim Fifel, Aleksandar Videnovic
A growing body of work is investigating the safety and efficacy of light in Parkinson's disease (PD). Here we discuss the potential of this emerging therapy to improve both motor and non-motor symptoms of PD. We also highlight directions for future basic, translational, and clinical research that are critical for the development of mechanism-based protocols of light therapy in PD.
March 24, 2018: Trends in Neurosciences
Mark S Cembrowski, Vilas Menon
The brain is an organ of immense complexity. Next-generation RNA sequencing (RNA-seq) is becoming increasingly popular in the deconstruction of this complexity into distinct classes of 'cell types'. Notably, in addition to revealing the organization of this distinct cell-type landscape, the technology has also begun to illustrate that continuous variation can be found within narrowly defined cell types. Here we summarize the evidence for graded transcriptomic heterogeneity being present, widespread, and functionally relevant in the nervous system...
March 22, 2018: Trends in Neurosciences
Sara N Burke, Leslie S Gaynor, Carol A Barnes, Russell M Bauer, Jennifer L Bizon, Erik D Roberson, Lee Ryan
A predominant view of perirhinal cortex (PRC) and postrhinal/parahippocampal cortex (POR/PHC) function contends that these structures are tuned to represent objects and spatial information, respectively. However, known anatomical connectivity, together with recent electrophysiological, neuroimaging, and lesion data, indicate that both brain areas participate in spatial and nonspatial processing. Instead of content-based organization, the PRC and PHC/POR may participate in two computationally distinct cortical-hippocampal networks: one network that is tuned to process coarse information quickly, forming gist-like representations of scenes/environments, and a second network tuned to process information about the specific sensory details that are necessary for discrimination across sensory modalities...
March 16, 2018: Trends in Neurosciences
Lakshmi Sundararajan, David M Miller
Two recent studies by Meltzer et al. and Ziegler et al. use Drosophila larvae to demonstrate that cell-autonomous regulation of lipid biosynthesis defines the complexity and function of highly branched nociceptive neurons. Their findings show that lipid biosynthesis in the neuron is fine-tuned for optimal dendrite morphology and sensitivity.
March 13, 2018: Trends in Neurosciences
David A Gallegos, Urann Chan, Liang-Fu Chen, Anne E West
Neurons are dynamic cells that respond and adapt to stimuli throughout their long postmitotic lives. The structural and functional plasticity of neurons requires the regulated transcription of new gene products, and dysregulation of transcription in either the developing or adult brain impairs cognition. We discuss how mechanisms of chromatin regulation help to orchestrate the transcriptional programs that underlie the maturation of developing neurons and the plasticity of adult neurons. We review how chromatin regulation acts locally to modulate the expression of specific genes and more broadly to coordinate gene expression programs during transitions between cellular states...
March 9, 2018: Trends in Neurosciences
Jeremy M Henley, Ruth E Carmichael, Kevin A Wilkinson
Post-translational modification of substrate proteins by SUMO conjugation regulates a diverse array of cellular processes. While predominantly a nuclear protein modification, there is a growing appreciation that SUMOylation of proteins outside the nucleus plays direct roles in controlling synaptic transmission, neuronal excitability, and adaptive responses to cell stress. Furthermore, alterations in protein SUMOylation are observed in a wide range of neurological and neurodegenerative diseases, and several extranuclear disease-associated proteins have been shown to be directly SUMOylated...
March 9, 2018: Trends in Neurosciences
Jean M Hébert, Jan Vijg
Current antiaging strategies focusing on druggable targets have met with relatively limited success to date. Replacement of cells, tissues, and organs could provide an alternative means for targeting age-induced damage and potentially eliminating some of it. However, before this is a viable option, numerous challenges need to be addressed. Most notably, whether the brain, which defines our self-identity, is amenable to replacement therapies is unclear. Here, we consider whether progressive cell replacement is a potential approach to reverse brain aging without grossly altering function...
March 8, 2018: Trends in Neurosciences
Richard D Palmiter
The parabrachial nucleus (PBN), which is located in the pons and is dissected by one of the major cerebellar output tracks, is known to relay sensory information (visceral malaise, taste, temperature, pain, itch) to forebrain structures including the thalamus, hypothalamus, and extended amygdala. The availability of mouse lines expressing Cre recombinase selectively in subsets of PBN neurons and viruses for Cre-dependent gene expression is beginning to reveal the connectivity and functions of PBN component neurons...
May 2018: Trends in Neurosciences
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