Search

Frontal area MOs (secondary motor area) is a key brain structure in rodents for making decisions based on sensory evidence and on reward value. In behavioral tasks, its neurons can encode sensory stimuli, upcoming choices, expected rewards, ongoing actions, and recent outcomes. However, the information encoded, and the nature of the resulting code, may depend on the task being performed. We recorded MOs population activity using two-photon calcium imaging, in a task requiring mice to integrate sensory evidence with reward value. Mice turned a wheel to report the location of a visual stimulus following a delay period, to receive a reward whose size varied over trial blocks. MOs neurons encoded multiple task variables, but not all of those seen in other tasks. In the delay period, the MOs population strongly encoded the stimulus side but did not significantly encode the reward-size block. A correlation of MOs activity with upcoming choice could be explained by a common effect of stimulus on those two correlates. After the wheel turn and the feedback, the MOs population encoded choice side and choice outcome jointly and nonlinearly according to an exclusive-or (XOR) operation. This nonlinear operation would allow a downstream linear decoder to infer the correct choice side (i.e., the side that would have been rewarded) even on zero contrast trials, when there had been no visible stimulus. These results indicate that MOs neurons flexibly encode some but not all variables that determine behavior, depending on task. Moreover, they reveal that MOs activity can reflect a nonlinear combination of these behavioral variables, allowing simple linear inference of task events that would not have been directly observable.

The striatum plays critical roles in visually-guided decision-making and receives dense axonal projections from midbrain dopamine neurons. However, the roles of striatal dopamine in visual decision-making are poorly understood. We trained male and female mice to perform a visual decision task with asymmetric reward payoff, and we recorded the activity of dopamine axons innervating striatum. Dopamine axons in the dorsomedial striatum (DMS) responded to contralateral visual stimuli and contralateral rewarded actions. Neural responses to contralateral stimuli could not be explained by orienting behavior such as eye movements. Moreover, these contralateral stimulus responses persisted in sessions where the animals were instructed to not move to obtain reward, further indicating that these signals are stimulus-related. Lastly, we show that DMS dopamine signals were qualitatively different from dopamine signals in the ventral striatum (VS), which responded to both ipsilateral and contralateral stimuli, conforming to canonical prediction error signaling under sensory uncertainty. Thus, during visual decisions, DMS dopamine encodes visual stimuli and rewarded actions in a lateralized fashion, and could facilitate associations between specific visual stimuli and actions. SIGNIFICANCE STATEMENT While the striatum is central to goal-directed behavior, the precise roles of its rich dopaminergic innervation in perceptual decision-making are poorly understood. We found that in a visual decision task, dopamine axons in the dorsomedial striatum (DMS) signaled stimuli presented contralaterally to the recorded hemisphere, as well as the onset of rewarded actions. Stimulus-evoked signals persisted in a no-movement task variant. We distinguish the patterns of these signals from those in the ventral striatum (VS). Our results contribute to the characterization of region-specific dopaminergic signaling in the striatum and highlight a role in stimulus-action association learning.

Near-neutral aqueous electrolytes are to be preferred for the development of sustainable electrochemical energy conversion and storage devices. Protons are inherent to these electrolytes and their reactivity towards the electrode material extends beyond their own reduction, especially when reversible proton insertion takes place in the bulk electrode material from acidic or buffered electrolytes. However, a still burning question regards whether reversible proton insertion persists when working in unbuffered mild aqueous electrolytes, and if so, with which consequences on the functioning of the electrode material. Here, we address this issue by examining TiO2 as a model insertion electrode in a range of mild aqueous electrolytes. Through a combination of experiments, modelling and multiphysics simulations, we demonstrate that, in a KCl-based electrolyte, water acts as proton donor to support reversible insertion of protons in TiO2, while in a NH4Cl-based aqueous electrolyte, the proton donor is NH4+. Moreover, we establish that strong pH gradients develop at the electrode interface during proton insertion/disinsertion, highlighting their dependence on the proton donor/acceptor and rationalizing their impact on the electrode voltage. Overall, this work provides a comprehensive framework of proton-insertion coupled electron transfer (PICET) that can be easily generalised to other electrode materials.

For high-value components, reusability is often an important design consideration. For adhesively joined parts, the disassembly mechanism can be a key factor, and in some cases the thermal degradability of adhesives determines the reusability and recyclability of the components. After use, components that can be easily separated are generally more easily reused, but this requires controlled and well-understood adhesive degradation. Here, polymer nanocomposites based on epoxy resin and cellulose nanocrystals (CNCs) were fabricated, and their properties were examined as degradable adhesives. The distribution of CNCs within the epoxy resin was investigated by electron microscopy and mass spectroscopy. By incorporating CNCs into epoxy matrices, the shear strength of nanocomposites was improved by 31% and the effective thermal degradation temperature was reduced by 40 °C. Additionally, chemical analysis by X-ray photoelectron spectroscopy showed that sulfonate groups on the surface of CNCs play a critical role over improving the mechanical properties, while thermally induced breakage of these bonds mediates the thermal degradation of the nanocomposite.

Cholinergic projections from the medial habenula (MHb) to the interpeduncular nucleus (IPN) have been studied for their complex contributions to nicotine addiction and have been implicated in nicotine reinforcement, aversion, and withdrawal. While it has been established that MHb cholinergic projections corelease glutamate, no direct evidence has demonstrated a role for this glutamate projection in nicotine consumption. In the present study, a novel floxedSlc17a7[vesicular glutamate transporter 1 (VGLUT1)] mouse was generated and used to create conditional knock-out (cKO) mice that lack VGLUT1 in MHb cholinergic neurons. Loss ofSlc17a7expression in ventral MHb cholinergic neurons was validated using fluorescentin situhybridization, and immunohistochemistry was used to demonstrate a corresponding reduction of VGLUT1 protein in cholinergic terminals in the IPN. We also used optogenetics-assisted electrophysiology to evoke EPSCs in IPN and observed a reduction of glutamatergic currents in the cKO, supporting the functional disruption of VGLUT1 in MHb to IPN synapses. cKO mice exhibited no gross phenotypic abnormalities and displayed normal thigmotaxis and locomotor behavior in the open-field assay. When trained to lever press for food, there was no difference between control and cKO. However, when tested in a nicotine self-administration procedure, we found that the loss of VGLUT1-mediated glutamate corelease led to increased responding for nicotine. These findings indicate that glutamate corelease from ventral MHb cholinergic neurons opposes nicotine self-administration, and provide additional support for targeting this synapse to develop potential treatments for nicotine addiction.

Transcriptomics has revealed the exquisite diversity of cortical inhibitory neurons1–7, but it is not known whether these fine molecular subtypes have correspondingly diverse activity patterns in the living brain. Here, we show that inhibitory subtypes in primary visual cortex (V1) have diverse correlates with brain state, but that this diversity is organized by a single factor: position along their main axis of transcriptomic variation. We combined in vivo 2-photon calcium imaging of mouse V1 with a novel transcriptomic method to identify mRNAs for 72 selected genes in ex vivo slices. We used transcriptomic clusters (t-types)4 to classify inhibitory neurons imaged in layers 1-3 using a three-level hierarchy of 5 Families, 11 Classes, and 35 t-types. Visual responses differed significantly only across Families, but modulation by brain state differed at all three hierarchical levels. Nevertheless, this diversity could be predicted from the first transcriptomic principal component, which predicted a cell type’s brain state modulation and correlations with simultaneously recorded cells. Inhibitory t-types with narrower spikes, lower input resistance, weaker adaptation, and less axon in layer 1 as determined in vitro8 fired more in resting, oscillatory brain states. Transcriptomic types with the opposite properties fired more during arousal. The former cells had more inhibitory cholinergic receptors, and the latter more excitatory receptors. Thus, despite the diversity of V1 inhibitory neurons, a simple principle determines how their joint activity shapes state-dependent cortical processing.

SUMMARYThe medial prefrontal cortex (mPFC) is necessary for executing many learned associations between stimuli and movement. It is unclear, however, whether activity in the mPFC reflects sensory or motor aspects of sensorimotor associations and whether it evolves gradually during learning. To address these questions, we recorded cortical activity with widefield calcium imaging while mice learned a visuomotor task. The task involved associating a visual stimulus with a forelimb movement. After learning, the mPFC showed stimulus-evoked activity both during task performance and during passive viewing, when the stimulus evoked no action. This stimulus-evoked activity closely tracked behavioral performance across training, exhibiting jumps between training days. Electrophysiological recordings localized this activity to the secondary motor and anterior cingulate cortex. We conclude that learning a visuomotor task promotes a route for visual information to reach the prefrontal cortex, which develops responses to the relevant visual stimuli even outside the context of the task.

Correlates of sensory stimuli and motor actions are found in multiple cortical areas, but such correlates do not indicate whether these areas are causally relevant to task performance. We trained mice to discriminate visual contrast and report their decision by steering a wheel. Widefield calcium imaging and Neuropixels recordings in cortex revealed stimulus-related activity in visual (VIS) and frontal (MOs) areas, and widespread movement-related activity across the whole dorsal cortex. Optogenetic inactivation biased choices only when targeted at VIS and MOs,proportionally to each site's encoding of the visual stimulus, and at times corresponding to peak stimulus decoding. A neurometric model based on summing and subtracting activity in VIS and MOs successfully described behavioral performance and predicted the effect of optogenetic inactivation. Thus, sensory signals localized in visual and frontal cortex play a causal role in task performance, while widespread dorsal cortical signals correlating with movement reflect processes that do not play a causal role.

Sensory cortices can be affected by stimuli of multiple modalities and are thus increasingly thought to be multisensory. For instance, primary visual cortex (V1) is influenced not only by images but also by sounds. Here we show that the activity evoked by sounds in V1, measured with Neuropixels probes, is stereotyped across neurons and even across mice. It is independent of projections from auditory cortex and resembles activity evoked in the hippocampal formation, which receives little direct auditory input. Its low-dimensional nature starkly contrasts the high-dimensional code that V1 uses to represent images. Furthermore, this sound-evoked activity can be precisely predicted by small body movements that are elicited by each sound and are stereotyped across trials and mice. Thus, neural activity that is apparently multisensory may simply arise from low-dimensional signals associated with internal state and behavior.

The brain should be best able to associate distinct behavioral responses to sensory stimuli if these stimuli evoke population firing patterns that are close to orthogonal. To investigate whether task training orthogonalizes population codes in primary visual cortex (V1), we measured the orientation tuning of 4,000-neuron populations in mouse V1 before and after training on a visuomotor task. The effect of task training on population codes could be captured by a simple mathematical transformation of firing rates, which suppressed responses to motor-associated stimuli, but only in cells responding to them at intermediate levels. This transformation orthogonalized the representations of the task orientations by sparsening the population responses to these stimuli. The strength of response transformation varied from trial to trial, suggesting a dynamic circuit mechanism rather than static synaptic plasticity. These results indicate a simple process by which visuomotor associations orthogonalize population codes as early as in primary visual cortex.

To interpret the world and make accurate perceptual decisions, the brain must combine information across sensory modalities, For instance, it must combine vision and hearing to localize objects based on their image and sound. Probability theory suggests that evidence from multiple independent cues should be combined additively 1, but it is unclear whether mice and other mammals do this 2–6, and the cortical substrates of multisensory integration are uncertain 7. Here we show that to localize a stimulus mice combine auditory and visual spatial cues additively, a computation supported by unisensory processing in auditory and visual cortex and additive multisensory integration in frontal cortex. We developed an audiovisual localization task where mice turn a wheel to indicate the joint position of an image and a sound. Scanning optogenetic inactivation of dorsal cortex 8–11 showed that auditory and visual areas contribute unisensory information, whereas frontal cortex (secondary motor area, MOs) contributes multisensory information to the mouse’s decision, Neuropixels recordings of >10,000 neurons indicated that neural activity in MOs reflects an additive combination of visual and auditory signals. An accumulator model 1,12,13 applied to the sensory representations of MOs neurons reproduced behaviourally observed choices and reaction times. This suggests that MOs integrates information from multiple sensory cortices, providing a signal that is then transformed into a binary decision by a downstream accumulator.

Recording many neurons for a long time The ultimate aim of chronic recordings is to sample from the same neuron over days and weeks. However, this goal has been difficult to achieve for large populations of neurons. Steinmetz et al. describe the development and testing of Neuropixels 2.0. This new electrophysiological recording tool is a miniaturized, high-density probe for both acute and long-term experiments combined with sophisticated software algorithms for fully automatic post hoc computational stabilization. The technique also provides a strategy for extending the number of recorded sites beyond the number of available recording channels. In freely moving animals, extremely large numbers of individual neurons could thus be followed and tracked with the same probe for weeks and occasionally months. Science , this issue p. eabf4588

Rechargeable aqueous aluminium batteries are the subject of growing interest, however, the charge storage mechanisms at manganese oxide-based cathodes remain poorly understood. In essense, every study proposes a different mechanism. Here, an in situ spectroelectrochemical methodology is used to unambiguously demonstrate that reversible proton-coupled MnO

Functional ultrasound imaging (fUSI) is an appealing method for measuring blood flow and thus infer brain activity, but it relies on the physiology of neurovascular coupling and requires extensive signal processing. To establish to what degree fUSI trial-by-trial signals reflect neural activity, we performed simultaneous fUSI and neural recordings with Neuropixels probes in awake mice. fUSI signals strongly correlated with the slow (