Volume 26 Issue 6, June 2023

As Nature Neuroscience celebrates its 25th anniversary, we are having conversations with both established leaders in the field and those earlier in their careers to discuss how neuroscience has evolved and where it is heading. This month, we are talking to Lucina Q. Uddin, professor-in-residence at Psychiatry and Biobehavioral Sciences at the University of California Los Angeles and the 2022–2023 Chair of the Diversity & Inclusivity Committee for the Organization for Human Brain Mapping. She uses neuroimaging to study brain networks that support behavior in typically developing children and children with autism. She spoke with me about how she became interested in neuroscience, her career trajectory, and personal experiences that led to her efforts in promoting diversity, equity and inclusion.

A study by Holstein-Rønsbo, Gan et al. published in this issue of Nature Neuroscience adds another dimension to the ‘glymphatic’ story — the role of functional hyperemia facilitating perivascular flow of cerebrospinal fluid along pial arteries.

Psychedelics induce fast and long-lasting antidepressant effects and neuronal plasticity, but their hallucinogenic effects limit their use. We show that, in mice, psychedelics bind directly to TrkB (the brain-derived neurotrophic factor (BDNF) receptor) with high affinity and promote BDNF-mediated plasticity and antidepressant-like effects, whereas their hallucinogenic-like effects are independent of TrkB binding.

Using long-term brain recordings in patients with chronic pain, we identified objective biomarkers of real-world subjective pain intensity over many months. Spontaneous chronic pain states were predicted most reliably by sustained changes in the activity of the orbitofrontal cortex, whereas acute pain was most associated with signals from the anterior cingulate cortex.

Sleep helps to stabilize long-term memories, possibly through the temporal synchronization of neuronal activity in different brain regions. Intracranial stimulation during sleep using prefrontal electric pulses, precisely timed with slow-wave activities in the medial temporal lobe, enhanced the coupling of neuronal oscillations across regions of the human brain and improved memory performance.

Genome-wide association studies for brain and behavioral traits have provided insights but also present challenges related to privacy and misuse. We discuss these ethical issues and how to mitigate potential negative consequences.

The immune system plays a critical role in neurodegenerative diseases. Resident and peripheral immune cells contribute to disease progression. Here, the authors review the role of peripheral immune cells both when infiltrating the CNS or when remaining in the periphery.

The authors associate a novel genomic risk score with a broad set of psychiatric symptoms in children. They trace the impact of associated genes on cerebellar developmental processes that originate in fetal life and endure through early adolescence.

Sun et al. analyzed 22,514 human brain vascular single-nucleus transcriptomes from 428 individuals and uncovered AD-related gene expression and cell–cell interaction linked to genetics, as well as vascular dysfunction in APOE-associated cognitive decline.

Reconstitution of TDP-43 filaments that exhibit sequence and morphological features similar to those found in the brain helps to uncover a new mechanism for the formation and propagation of pathology in amyotrophic lateral sclerosis and other neurodegenerative diseases.

Endocannabinoids are important modulators of synaptic transmission, although their mechanism of release is unknown. In this study, the authors found that endocannabinoid postsynaptic release is mediated by synucleins via a synuclein-dependent and SNARE-dependent mechanism.

The molecular diversity of microglia has been described. Here the authors show that ARG1-expressing microglia are enriched in phagocytic inclusions and are involved in hippocampal innervation and spine maturation in mice. ARG1-expressing microglia also modulate cognition in a sex-dependent manner.

Increased neuronal activity and reduced sleep quality emerge in the early stages of Alzheimer’s disease (AD). Calafate et al. show that the sleep–active hypothalamic MCH system is involved in neuronal homeostasis but fails in the early stages of AD.

Moliner et al. show that psychedelics directly bind to the BDNF receptor TrkB with high affinity and promote BDNF-mediated plasticity and antidepressant-like effects, whereas their hallucinogenic-like effects are independent of TrkB binding.

Holstein-Rønsbo et al. show that functional hyperemia increases glymphatic CSF inflow and clearance. Direct stimulation of vascular smooth muscle cells, in the absence of neuronal activation, similarly enhances glymphatic flow.

Behaviors often consist of sequences of component actions. Cury and Axel identify distinct classes of sensory neurons that control the transitions between the components of egg laying in the fly that afford this behavior an adaptive flexibility.

This study tests a key hypothesis of cerebellar motor correction, showing that inputs to the cerebellum that drive errors during skilled movements are rapidly adjusted over trials to enhance motor accuracy.

Hahamy et al. demonstrate that, at the transitions between narrative events, the human brain reactivates past information that is relevant for the understanding of the current narrative stage.

Using the chronic brain recordings in the anterior cingulate cortex and orbitofrontal cortex in four participants with intractable chronic pain, this study identified objective neural biomarkers of subjective pain experience.

Geva-Sagiv et al. performed real-time closed-loop intracranial stimulation in human sleep. Brief prefrontal pulses, precisely timed with MTL slow-wave active periods, led to correlated enhancements in sleep oscillation coupling and memory accuracy.

By reconstructing the complete dendrites and axons for nearly 2,000 neurons in PFC, Gao et al. comprehensively classified dendrite morphology, revealed the relationship between dendrites and axons and mapped the mesoscopic PFC neural network.