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Hierarchical Assembly of Fluorinated BODIPY-Based Nanoribbons for Highly Efficient Metal-Free Photocatalytic Hydrogen Production

Major Turing computing award goes to quantum science for first time

Organic Cation Influence on Organic–Inorganic Thermal Equilibration within 2D Metal Halide Perovskites

Botanical mystery solved: how plants make a crucial malaria drug

A Photoactivatable Glycoenzyme Platform for Spatiotemporally Controlled, Protein-Selective, and In Vivo Glycan Editing

Upcycling of Vulcanized Rubber via Controlled Backbone Cleavage and Functionalization

Mystery of how plants make a family of medicinal molecules has been solved

Delayed, Reduced, and Redundant: Information Processing of Prediction Errors during Human Sleep

During sleep, the human brain transitions to a “sentinel processing mode,” enabling the continued processing of environmental stimuli despite the absence of consciousness. We employed advanced information-theoretic analyses, including mutual information (MI) and co-information (co-I), alongside event-related potential (ERP) and temporal generalization analyses (TGA), to characterize auditory prediction error processing across wakefulness and sleep. We hypothesized that a shared neural code would be present across sleep stages, with deeper sleep being associated with reduced information content and increased information redundancy. Twenty-nine participants (15 women) underwent an auditory “local–global” oddball paradigm during wakefulness and an 8 h sleep opportunity monitored via polysomnography. We focused on “local” mismatch responses to a deviating fifth tone after four standards. ERP analyses showed that prediction error processing continued throughout all sleep stages (N1–N3, REM). Mutual information analyses revealed a substantial reduction in encoded prediction error information particularly during N3 and REM, although ERP amplitudes increased with deeper NREM sleep. We also observed delayed information encoding during sleep, and co-information analyses showed neural dynamics became increasingly redundant with increasing sleep depth. TGA revealed a largely shared neural code between N2 and N3, though it differed between wakefulness and sleep. We demonstrate how the neural code of the “sentinel processing mode” changes from wake to light to deep sleep and REM, characterized by delayed processing, more redundant and less rich neural information in the human cortex as consciousness wanes. This altered stimulus processing reveals how neural information evolves with variations in consciousness across the night.

One-Dimensional and Pseudo-Two-Dimensional Helicene Covalent Organic Frameworks

Ultrasound-Activated Prodrugs for Tumor-Specific Immunotherapy

Differential Coding of Associative Memory Information in the Macaque Lateral Prefrontal Cortex and Hippocampus

The prefrontal cortex (PFC) and hippocampus (HPC) reportedly play crucial roles in the flexible use of stored information according to context. However, it remains unclear whether and how their neural representations differ during the context-guided retrieval. To solve this problem, we examined neural activity in the lateral PFC (lPFC, 470 neurons), medial PFC (mPFC, 322 neurons), and HPC (456 neurons) of three male macaques performing an item-location association memory task. The task required the animals to remember the location of a firstly presented item-cue relative to a background image that was later shown with a tilt as a context-cue. Population decoding analyses using all recorded neurons suggested that the lPFC and HPC (but not the mPFC) represented substantial task-related information. However, the represented contents differed between the two areas, both before and after the context-cue. Before the context-cue, the lPFC represented only the location retrieved from the item-cue, while the HPC also represented the item-cue itself. After the context-cue, the lPFC demonstrated a selective representation of the target-location regardless of the context-cue. In contrast, the HPC represented the three task-related pieces of information equivalently. These results suggest that the lPFC selectively represents goal-directed information at that moment among task-related information, while the HPC automatically represents a task event and its mnemonically linked information, implying complementary functional roles of the two brain regions as “regulator” and “supplier” in the context-guided memory process.

Evolution

Vesicular Glutamate Release Is Necessary for Neural Tube Formation

The brain and spinal cord originate from a neural tube that is preceded by a flat structure known as the neural plate during early embryogenesis. In humans, failure of the neural plate to convert into a tube by the fourth week of pregnancy leads to neural tube defects (NTDs), birth defects with serious neurological consequences. The signaling mechanisms governing the process of neural tube morphogenesis are unclear. Here we show that in Xenopus laevis embryos, glutamate is released during neural plate folding in a Ca 2+ and vesicular glutamate transporter-1 (VGluT1)-dependent manner. Vesicular release of glutamate elicits Ca 2+ transients in neural plate cells that correlate with activation of Erk1/2. Knocking down or out VGluT1, globally or neural tissue-specifically, leads to NTDs and increased expression of Sox2, neural stem cell transcription factor, and neural plate cell proliferation. Exposure during early pregnancy to neuroactive drugs that disrupt these signaling mechanisms might increase the risk of NTDs in offspring.

Neural Representations of Reward-Related Memories Shift across Development

Rewards signal information in the environment that is valuable and thus useful to remember. Rewards benefit memory across development, but how reward-associated memories are represented in the brain has not been well characterized. Here we conducted pattern similarity analyses of fMRI data in male and female participants aged 8–25 to elucidate how neural representations in key memory-related brain areas are influenced by reward and how these relationships change across childhood and adolescence. We found that reward information was reflected in pattern similarity during encoding in the ventral temporal cortex and in changes in similarity from encoding to retrieval in anterior hippocampus (aHC). Strikingly, aHC reward-sensitive representations also varied with age such that adults’ memory benefitted from stability of hippocampal representations, whereas younger participants’ memory improvements were associated with greater drift in representations over time. Moreover, across all participants, reward-related univariate activation in the ventral tegmental area was associated with a greater tendency toward representational drift in aHC. Taken together, our findings demonstrate that reward modulates neural memory representations and that the representational patterns supporting reward-motivated memory shift with age.

Dynamic Modulation of Beta-Band Oscillations in the LGN and Their Role in Visual Processing

Neuronal oscillations are a ubiquitous feature of thalamocortical networks and can be dynamically modulated across processing states, enabling thalamocortical communication to flexibly adapt to varying environmental and behavioral demands. The lateral geniculate nucleus (LGN), like all thalamic nuclei, engages in reciprocal synaptic interactions with the cortex, relaying retinal information to and receiving feedback input from primary visual cortex (V1). While retinal excitation is the primary driver of LGN activity, retinal synapses represent a minority of the total synaptic input onto LGN neurons, allowing for both retinogeniculate and geniculocortical signals to be influenced by nonretinal sources. To gain a holistic view of network processing in the geniculocortical pathway, we performed simultaneous extracellular recordings from the LGN and V1 of behaving macaque monkeys (two male, four female), measuring local field potentials (LFPs) and spiking activity. These recordings revealed prominent beta-band oscillations coherent between the LGN and V1 that influenced spike timing in the LGN and were statistically consistent with a feedforward process from the LGN to V1. These thalamocortical oscillations were suppressed by visual stimulation, spatial attention, and behavioral arousal, strongly suggesting that these oscillations are not a feature of active visual processing. Instead, they appear analogous to occipital lobe, alpha oscillations recorded in humans and may represent a signature of signal suppression that occurs during periods of low engagement or active distractor suppression.

Circuit Organization of the Forelimb-Related M2-to-M1 Corticocortical Pathway in the Mouse

Communication from secondary (M2, premotor) to primary (M1) motor cortex is implicated in forelimb motor control. We investigated the underlying synaptic circuits in this corticocortical pathway in male and female mice using cell-type-specific optogenetic-electrophysiology methods, focusing on identifying the cell-type-specific synaptic connections in the excitatory and feedforward inhibitory circuits impinging on cervically projecting M1 corticospinal neurons. In forelimb M1 brain slices, recordings from layer (L)5B corticospinal neurons during brief photostimulation of M2 axons showed strong monosynaptic excitatory currents that, although accompanied by potent feedforward inhibitory currents, were capable of evoking action potentials (APs) in most neurons. In contrast, responses in L2/3 pyramidal neurons were generally much weaker. Parvalbumin (PV)-expressing neurons, particularly in deeper layers, showed direct excitation from M2 axons without feedforward inhibition and could fire APs robustly. Somatostatin (SST) neurons received generally weak inputs, whereas vasoactive intestinal protein (VIP) and neuron-derived neurotrophic factor (Ndnf) neurons received stronger excitation and inhibition from M2 axons. Corticospinal neurons received little or no local inhibition from Ndnf and VIP interneurons but relatively strong soma-targeting PV and dendrite-targeting SST inhibitory inputs, as functionally imaged by laser-scanning synaptic input mapping (“sCRACM”). The domains of PV and SST inputs were partly overlapping around the corticospinal somata but broader for PV and more vertical for SST inputs. Collectively, the results provide a working model for the cell-type-specific synaptic circuits of this “top–down” corticocortical pathway, organized around direct M2 excitation and PV-mediated inhibition of M1 corticospinal neurons.

Rapid Motor Inhibition as a Mechanism to Prevent Outdated Movements

Sudden environmental changes can render planned hand movements suboptimal or even counterproductive. To prevent the execution of outdated motor plans, the motor system may transiently inhibit actions following salient changes, allowing time to evaluate alternatives. While such a mechanism is well established for eye movements, its applicability to hand movements remains unclear. Here, we present findings from three online behavioral experiments and two lab-based replications designed to probe key features of this mechanism in manual responses: reflexive inhibition, temporal precedence, complete movement updating, and sensitivity to saliency. Participants of either sex performed rapid sequential tapping movements toward onscreen targets. At an unpredictable time, either a relevant change (a target displacement) or an irrelevant change (a brief luminance flash) occurred. We measured movement initiation rates following these changes and compared them with a no-change baseline. A significant transient inhibition of movement initiation followed both relevant and irrelevant changes. This inhibition preceded observable updates to the movement plan. At the time of inhibition release, the update to a movement plan was complete. Across experiments, we observed stronger inhibitory effects for more salient changes. The lab-based replication confirmed that the latency of this inhibitory response aligns with visuomotor reaction times. These results support the existence of a general-purpose, rapid inhibitory mechanism in hand movements analogous to inhibition in the oculomotor system. We propose that such inhibition provides a reflexive, domain-general safeguard against obsolete actions following unexpected changes.

Attenuated Single Neuron and Network Hyperexcitability Following MicroRNA-134 Inhibition in Mice with Drug-Resistant Temporal Lobe Epilepsy

The multifactorial pathophysiology of acquired epilepsies lends itself to a multitargeting therapeutic approach. MicroRNAs (miRNA) are short noncoding RNAs that individually can negatively regulate dozens of protein-coding transcripts. Previously, we reported that central injection of antisense oligonucleotides targeting microRNA-134 (Ant-134) shortly after status epilepticus potently suppressed the development of recurrent spontaneous seizures in rodent models of temporal lobe epilepsy. The mechanism(s) of these antiseizure effects remain, however, incompletely understood. Here we show that intracerebroventricular microinjection of Ant-134 in male mice with preexisting epilepsy caused by intra-amygdala kainic acid-induced status epilepticus potently reduces the occurrence of spontaneous seizures. Recordings from ex vivo brain slices collected 2–4 d after Ant-134 injection in epileptic mice detected a number of electrophysiological phenotypic changes consistent with reduced excitability. Specifically, Ant-134 reduced action potential bursts after current injection in CA1 neurons and reduced excitatory postsynaptic current frequencies in CA1 neurons. Ant-134 also reduced general network excitability, including attenuating proexcitatory CA1 responses to Schaffer collateral stimulation in hippocampal slices from epileptic mice. Together, the present study demonstrates inhibiting miR-134 reduces single neuron and network hyperexcitability in mice and extends support for this approach to treat drug-resistant epilepsies.

Human Beta Oscillations Reflect Magnitude and Fidelity of Priority Shifts in Working Memory

Flexible prioritization in working memory (WM) is supported by neural oscillations in frontal and sensory brain areas, but the roles of different oscillations remain poorly understood. Recordings in humans suggest an interplay between prefrontal slow frequency (2–8 Hz) and posterior alpha-band (10 Hz) oscillations regulating top-down control and retrieval of WM representations, respectively. Complementary work, primarily in nonhuman primates, suggests an additional role for beta (15–30 Hz) oscillations in clearing or inhibiting stimuli from entering WM. Here we investigated the role of neural oscillations in prioritizing WM content using electroencephalography (EEG) as participants (humans of any sex) performed a task requiring frequent priority switches between two memorized oriented bars. Behavioral performance revealed switch costs, which scaled with the angular distance between the two items, suggesting that priority shifts are modulated by shift magnitude. Time–frequency analyses revealed increased frontal theta (4–8 Hz) and decreased central-parietal beta (15–25 Hz) power during switches. Crucially, only beta power scaled with the magnitude of the priority shift and predicted the fidelity of neural decoding of the newly prioritized item during subsequent recall. Theta power, in contrast, was elevated on switch trials but did not vary with update magnitude or decoding strength, suggesting a more general role in signaling control demands. Our findings highlight a particular and previously overlooked role for beta-band oscillations in the flexible prioritization of WM content.

Controlled Retrieval Relies on Directed Interactions between Semantic Control Regions and Visual Cortex: MEG Evidence from Oscillatory Dynamics

To navigate the world, we store knowledge about relationships between concepts and retrieve this information flexibly to suit our goals. The semantic control network, comprising left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG), is thought to orchestrate this flexible retrieval by modulating sensory inputs. However, interactions between semantic control and input regions are not sufficiently understood. Moreover, pMTG's well-formed structural connections to IFG and visual cortex suggest it as a candidate region to integrate control and input processes. We used magnetoencephalography to investigate oscillatory dynamics during semantic decisions to pairs of words, when participants (both sexes) did or did not know the type of semantic relation between them. IFG showed increases and decreases in oscillatory activity to prior task knowledge, while pMTG only showed positive task knowledge effects. Furthermore, IFG provided sustained feedback to pMTG when task goals were known, while in the absence of goals this feedback was delayed until receiving bottom-up input from the second word. This goal-dependent feedback coincided with an earlier onset of feedforward signaling from visual cortex to pMTG, indicating rapid retrieval of task-relevant features. This pattern supports a model of semantic cognition in which pMTG integrates top-down control from IFG with bottom-up input from visual cortex to activate task-relevant semantic representations. Our findings elucidate the separate roles of anterior and posterior components of the semantic control network and reveal the spectro-temporal cascade of interactions between semantic and visual regions that underlie our ability to flexibly adapt cognition to the current goals.