Nature Reviews. Neuroscience

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Acetylcholine plays an essential role in fundamental aspects of cognition. Studies that have mapped the activity and functional connectivity of cholinergic neurons have shown that the axons of basal forebrain cholinergic neurons innervate the pallium with far more topographical and functional organization than was historically appreciated. Together with the results of studies using new probes that allow release of acetylcholine to be detected with high spatial and temporal resolution, these findings have implicated cholinergic networks in 'binding' diverse behaviours that contribute to cognition...

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The brain of modern humans has evolved remarkable computational abilities that enable higher cognitive functions. These capacities are tightly linked to an increase in the size and connectivity of the cerebral cortex, which is thought to have resulted from evolutionary changes in the mechanisms of cortical development. Convergent progress in evolutionary genomics, developmental biology and neuroscience has recently enabled the identification of genomic changes that act as human-specific modifiers of cortical development...

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Spectrins are cytoskeletal proteins that are expressed ubiquitously in the mammalian nervous system. Pathogenic variants in SPTAN1, SPTBN1, SPTBN2 and SPTBN4, four of the six genes encoding neuronal spectrins, cause neurological disorders. Despite their structural similarity and shared role as molecular organizers at the cell membrane, spectrins vary in expression, subcellular localization and specialization in neurons, and this variation partly underlies non-overlapping disease presentations across spectrinopathies...

With sweeping advances in precision delivery systems and manipulation of the genomes and transcriptomes of various cell types, medical biotechnology offers unprecedented selectivity for and control of a wide variety of biological processes, forging new opportunities for therapeutic interventions. This perspective summarizes state-of-the-art gene therapies enabled by recent innovations, with an emphasis on the expanding universe of molecular targets that govern the activity and function of primary sensory neurons and which might be exploited to effectively treat chronic pain...

The midbrain dopamine (mDA) system is composed of molecularly and functionally distinct neuron subtypes that mediate specific behaviours and are linked to various brain diseases. Considerable progress has been made in identifying mDA neuron subtypes, and recent work has begun to unveil how these neuronal subtypes develop and organize into functional brain structures. This progress is important for further understanding the disparate physiological functions of mDA neurons and their selective vulnerability in disease, and will ultimately accelerate therapy development...

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