Nature Reviews Neuroscience最新文献

The polarized and domain-specific distribution of membrane ion channels is essential for neuronal homeostasis, but delivery of these proteins to distal neuronal compartments (such as the axonal ends of peripheral sensory neurons) presents a logistical challenge. Recent developments have enabled the real-time imaging of single protein trafficking and the investigation of the life cycle of ion channels across neuronal compartments. These studies have revealed a highly regulated process involving post-translational modifications, vesicular sorting, motor protein-driven transport and targeted membrane insertion. Emerging evidence suggests that neuronal activity and disease states can dynamically modulate ion channel localization, directly influencing excitability. This Review synthesizes current knowledge on the spatiotemporal regulation of ion channel trafficking in both central and peripheral nervous system neurons. Understanding these processes not only advances our fundamental knowledge of neuronal excitability, but also reveals potential therapeutic targets for disorders involving aberrant ion channel distribution, such as chronic pain and neurodegenerative diseases.

In addition to their more studied cognitive and motor effects, neurodegenerative diseases are also associated with impairments in autonomic function — the regulation of involuntary physiological processes. These autonomic impairments manifest in different ways and at different stages depending on the specific disease. The neural networks responsible for autonomic regulation in the brain and body have characteristics that render them particularly susceptible to the prion-like spread of protein aggregation involved in neurodegenerative diseases. Specifically, the axons of these neurons — in both peripheral and central networks — are long and poorly myelinated axons, which make them preferential targets for pathological protein aggregation. Moreover, cortical regions integrating information about the internal state of the body are highly connected with other brain regions, which increases the likelihood of intersection with pathological pathways and prion-like spread of abnormal proteins. This leads to an autonomic ‘signature’ of dysfunction, characteristic of each neurodegenerative disease, that is linked to the affected networks and regions undergoing pathological aggregation.

Neuropathic pain is a debilitating condition caused by damage to the nervous system that results in changes along the pain pathway that lead to persistence of the pain sensation. Unremitting pain conditions are associated with maladaptive plasticity, disruption of neuronal activity that favours excitation over inhibition, and engagement of immune cells. The substantial progress made over the last two decades in the neuroimmune interaction research area points to a mechanistic role of spinal cord microglia, which are resident immune cells of the CNS. Microglia respond to and modulate neuronal activity during establishment and persistence of neuropathic pain states, and microglia–neuron pathways provide targets that can be exploited to attenuate abnormal neuronal activity and provide pain relief.

Even the most highly-trained observers presented with identical choice-relevant stimuli will reliably exhibit substantial trial-to-trial variability in the timing and accuracy of their choices. Despite being a pervasive feature of choice behaviour and a prominent phenotype for numerous clinical disorders, the capability to disentangle the sources of such intra-individual variability (IIV) remains limited. In principle, computational models of decision-making offer a means of parsing and estimating these sources, but methodological limitations have prevented this potential from being fully realized in practice. In this Review, we first discuss current limitations of algorithmic models for understanding variability in decision-making behaviour. We then highlight recent advances in behavioural paradigm design, novel analyses of cross-trial behavioural and neural dynamics, and the development of neurally grounded computational models that are now making it possible to link distinct components of IIV to well-defined neural processes. Taken together, we demonstrate how these methods are opening up new avenues for systematically analysing the neural origins of IIV, paving the way for a more refined, holistic understanding of decision-making in health and disease.

A great deal of research in the neuroscience of music suggests that neural oscillations synchronize with musical stimuli. Although neural synchronization is a well-studied mechanism underpinning expectation, it has even more far-reaching implications for music. In this Perspective, we survey the literature on the neuroscience of music, including pitch, harmony, melody, tonality, rhythm, metre, groove and affect. We describe how fundamental dynamical principles based on known neural mechanisms can explain basic aspects of music perception and performance, as summarized in neural resonance theory. Building on principles such as resonance, stability, attunement and strong anticipation, we propose that people anticipate musical events not through predictive neural models, but because brain–body dynamics physically embody musical structure. The interaction of certain kinds of sounds with ongoing pattern-forming dynamics results in patterns of perception, action and coordination that we collectively experience as music. Statistically universal structures may have arisen in music because they correspond to stable states of complex, pattern-forming dynamical systems. This analysis of empirical findings from the perspective of neurodynamic principles sheds new light on the neuroscience of music and what makes music powerful.