Trends in Neurosciences
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TiNS Special Issue: Circuit Development and Remodeling.
Exercise, APOE genotype, and the evolution of the human lifespan.
We propose the hypothesis that the evolution of increased physical activity approximately 2 million years ago served to reduce the amyloid plaque and vascular burden of APOE ɛ4, relaxing genetic constraints on aging. This multidisciplinary approach links human evolution with health and provides a co...
Kaleidoscopic protein-protein interactions in the life and death of ataxin-1: new strategies against protein aggregation.
We discuss the paradigmatic example of ataxin-1 (Atx1), the protein responsible for neurodegenerative spinocerebellar ataxia type 1 (SCA1). This disease is part of the increasing family of pathologies caused by protein aggregation and misfolding. We discuss the importance of protein-protein interact...
Opening paths to novel analgesics: the role of potassium channels in chronic pain.
We review salient findings from expression, pharmacological, and genetic studies that have untangled a hitherto undervalued contribution of K⁺ channels in maladaptive pain signaling. These emerging data provide a framework to explain enigmatic pain syndromes and to design novel pharmacological treat...
A de novo convergence of autism genetics and molecular neuroscience.
We review recent studies and suggest that they have led to a convergence on three functional pathways: (i) chromatin remodeling; (ii) wnt signaling during development; and (iii) synaptic function. These pathways and genes significantly expand the neurobiological targets for study, and suggest a path...
Blurring the boundaries: developmental and activity-dependent determinants of neural circuits.
The human brain comprises approximately 100 billion neurons that express a diverse, and often subtype-specific, set of neurotransmitters and voltage-gated ion channels. Given this enormous complexity, a fundamental question is how is this achieved? The acquisition of neurotransmitter phenotype was v...
Neuronal circuits that regulate feeding behavior and metabolism.
Neurons within the central nervous system receive humoral and central (neurotransmitter or neuropeptide) signals that ultimately regulate ingestive behavior and metabolism. Recent advances in mouse genetics combined with neuroanatomical and electrophysiological techniques have contributed to a bette...
Interview with Edward S. Boyden.
Pain-related changes in the brain: diagnostic and therapeutic potentials.
Emerging evidence suggests that chronic pain is a disease that can alter brain function. Imaging studies have demonstrated structural remapping and functional reorganization of brain circuits under various pain conditions. In parallel, preclinical models have demonstrated that chronic pain causes lo...
Serotonin transporter gene, stress and raphe-raphe interactions: a molecular mechanism of depression.
We draw on recent discoveries in the functional neuroanatomy of the serotonergic dorsal raphe nucleus (DR) to propose such a mechanistic account. We argue that genetically produced variability in serotonin reuptake during stressor-induced raphe-raphe interactions alters the balance in the amygdala-v...