Anisotropic Composition and Mechanical Behavior of a Natural Thin-Walled Composite: Eagle Feather Shaft

Flight feather shafts are outstanding bioinspiration templates due to their unique light weight and their stiff and strong characteristics. As a thin wall of a natural composite beam, the keratinous cortex has evolved anisotropic features to support flight. Here, the anisotropic keratin composition, tensile response, dynamic properties of the cortex, and fracture behaviors of the shafts are clarified. The analysis of Fourier transform infrared (FTIR) spectra indicates that the protein composition of calamus cortex is almost homogeneous. In the middle and distal shafts (rachis), the content of the hydrogen bonds (HBs) and side-chain is the highest within the dorsal cortex and is consistently lower within the lateral wall. The tensile responses, including the properties and dominant damage pattern, are correlated with keratin composition and fiber orientation in the cortex. As for dynamic properties, the storage modulus and damping of the cortex are also anisotropic, corresponding to variation in protein composition and fibrous structure. The fracture behaviors of bent shafts include matrix breakage, fiber dissociation and fiber rupture on compressive dorsal cortex. To clarify, ‘real-time’ damage behaviors, and an integrated analysis between AE signals and fracture morphologies, are performed, indicating that calamus failure results from a straight buckling crack and final fiber rupture. Moreover, in the dorsal and lateral walls of rachis, the matrix breakage initially occurs, and then the propagation of the crack is restrained by ‘ligament-like’ fiber bundles and cross fiber, respectively. Subsequently, the further matrix breakage, interface dissociation and induced fiber rupture in the dorsal cortex result in the final failure.

Cortical glutamatergic projection neuron types contribute to distinct functional subnetworks

The cellular basis of cerebral cortex functional architecture remains not well understood. A major challenge is to monitor and decipher neural network dynamics across broad cortical areas yet with projection neuron (PN) type resolution in real time during behavior. Combining genetic targeting and wide-field imaging, we monitored activity dynamics of subcortical-projecting (PTFezf2) and intratelencephalic-projecting (ITPlxnD1) types across dorsal cortex of mice during multiple brain states and behaviors. ITPlxnD1 and PTFezf2 showed distinct activation patterns during wakeful resting, spontaneous movements, and upon sensory stimulation. Distinct ITPlxnD1 and PTFezf2 subnetworks dynamically tuned to different sensorimotor components of a naturalistic feeding behavior, and optogenetic inhibition of subnetwork nodes disrupted specific behavioral components. ITPlxnD1 and PTFezf2 projection patterns supported their subnetwork activation patterns. Our results suggest that, in addition to the concept of columnar organization, dynamic areal and PN type-specific subnetworks is a key feature of cortical functional architecture linking microcircuit components with global brain networks.

Excess interictal activity marks seizure prone cortical areas and mice in a genetic epilepsy model

Genetic epilepsies are often caused by variants in widely expressed genes, potentially impacting numerous brain regions and functions. For instance, gain-of-function (GOF) variants in the widely expressed Na+-activated K+ channel gene KCNT1 alter basic neurophysiological and synaptic properties of cortical neurons, leading to developmental epileptic encephalopathy. Yet, aside from causing seizures, little is known about how such variants reshape interictal brain activity, and how this relates to epileptic activity and other disease symptoms. To address this knowledge gap, we monitored neural activity across the dorsal cortex in a mouse model of human KCNT1-related epilepsy using in vivo, awake widefield Ca2+ imaging. We observed 52 spontaneous seizures and 1700 interictal epileptiform discharges (IEDs) in homozygous mutant (Kcnt1m/m) mice, allowing us to map their appearance and spread at high spatial resolution. Outside of seizures and IEDs, we detected ~46,000 events, representing interictal cortical activity, in both Kcnt1m/m and wild-type (WT) mice, and we classified them according to their spatial profiles. Spontaneous seizures and IEDs emerged within a consistent set of susceptible cortical areas, and seizures propagated both contiguously and non-contiguously within these areas in a manner influenced, but not fully determined, by underlying synaptic connectivity. Seizure emergence was predicted by a progressive concentration of total cortical activity within the impending seizure emergence zone. Outside of seizures and IEDs, similar events were detected in WT and Kcnt1m/m mice, suggesting that the spatial structure of interictal activity was largely preserved. Several features of these events, however, were altered in Kcnt1m/m mice. Most event types were briefer, and their intensity more variable, across Kcnt1m/m mice; mice showing more intense activity spent more time in seizure. Furthermore, the rate of events whose spatial profile overlapped with where seizures and IEDs emerged was increased in Kcnt1m/m mice. Taken together, these results demonstrate that an epilepsy-causing K+ channel variant broadly alters physiology. Yet, outside of seizures and IEDs, it acts not to produce novel types of cortical activity, but rather to modulate its amount. The areas where seizures and IEDs emerge show excessively frequent and intense interictal activity and the mean intensity of an individual's cortical activity predicts its seizure burden. These findings provide critical guidance for targeting future research and therapy development.

The dorsal visual pathway represents object-centered spatial relations for object recognition

Although there is mounting evidence that input from the dorsal visual pathway is crucial for object processes in the ventral pathway, the specific functional contributions of dorsal cortex to these processes remains poorly understood. Here, we hypothesized that dorsal cortex computes the spatial relations among an object's parts — a processes crucial for forming global shape percepts — and transmits this information to the ventral pathway to support object categorization. Using multiple functional localizers, we discovered regions in the intraparietal sulcus (IPS) that were selectively involved in computing object-centered part relations. These regions exhibited task-dependent functional connectivity with ventral cortex, and were distinct from other dorsal regions, such as those representing allocentric relations, 3D shape, and tools. In a subsequent experiment, we found that the multivariate response of posterior IPS, defined on the basis of part-relations, could be used to decode object category at levels comparable to ventral object regions. Moreover, mediation and multivariate connectivity analyses further suggested that IPS may account for representations of part relations in the ventral pathway. Together, our results highlight specific contributions of the dorsal visual pathway to object recognition. We suggest that dorsal cortex is a crucial source of input to the ventral pathway and may support the ability to categorize objects on the basis of global shape.

Patterns of Unilateral and Bilateral Projections From Layers 5 and 6 of the Auditory Cortex to the Inferior Colliculus in Mouse

The auditory cortex sends massive projections to the inferior colliculus, but the organization of this pathway is not yet well understood. Previous work has shown that the corticocollicular projection emanates from both layers 5 and 6 of the auditory cortex and that neurons in these layers have different morphological and physiological properties. It is not yet known in the mouse if both layer 5 and layer 6 project bilaterally, nor is it known if the projection patterns differ based on projection location. Using targeted injections of Fluorogold into either the lateral cortex or dorsal cortex of the inferior colliculus, we quantified retrogradely labeled neurons in both the left and right lemniscal regions of the auditory cortex, as delineated using parvalbumin immunostaining. After dorsal cortex injections, we observed that approximately 18–20% of labeled cells were in layer 6 and that this proportion was similar bilaterally. After lateral cortex injections, only ipsilateral cells were observed in the auditory cortex, and they were found in both layer 5 and layer 6. The ratio of layer 5:layer 6 cells after lateral cortex injection was similar to that seen after dorsal cortex injection. Finally, injections of different tracers were made into the two inferior colliculi, and an average of 15–17% of cells in the auditory cortex were double-labeled, and these proportions were similar in layers 5 and 6. These data suggest that (1) only the dorsal cortex of the inferior colliculus receives bilateral projections from the auditory cortex, (2) both the dorsal and lateral cortex of the inferior colliculus receive similar layer 5 and layer 6 auditory cortical input, and (3) a subpopulation of individual neurons in both layers 5 and 6 branch to innervate both dorsal cortices of the inferior colliculus.

Decoding of cortex-wide brain activity from local recordings of neural potentials

Objective. Electrical recordings of neural activity from brain surface have been widely employed in basic neuroscience research and clinical practice for investigations of neural circuit functions, brain-computer interfaces, and treatments for neurological disorders. Traditionally, these surface potentials have been believed to mainly reflect local neural activity. It is not known how informative the locally recorded surface potentials are for the neural activities across multiple cortical regions. Approach. To investigate that, we perform simultaneous local electrical recording and wide-field calcium imaging in awake head-fixed mice. Using a recurrent neural network model, we try to decode the calcium fluorescence activity of multiple cortical regions from local electrical recordings. Main results. The mean activity of different cortical regions could be decoded from locally recorded surface potentials. Also, each frequency band of surface potentials differentially encodes activities from multiple cortical regions so that including all the frequency bands in the decoding model gives the highest decoding performance. Despite the close spacing between recording channels, surface potentials from different channels provide complementary information about the large-scale cortical activity and the decoding performance continues to improve as more channels are included. Finally, we demonstrate the successful decoding of whole dorsal cortex activity at pixel-level using locally recorded surface potentials. Significance. These results show that the locally recorded surface potentials indeed contain rich information of the large-scale neural activities, which could be further demixed to recover the neural activity across individual cortical regions. In the future, our cross-modality inference approach could be adapted to virtually reconstruct cortex-wide brain activity, greatly expanding the spatial reach of surface electrical recordings without increasing invasiveness. Furthermore, it could be used to facilitate imaging neural activity across the whole cortex in freely moving animals, without requirement of head-fixed microscopy configurations.

Streptococcus pneumoniae rapidly translocates from the nasopharynx through the cribriform plate to invade and inflame the dura

The entry routes and translocation mechanisms of bacterial pathogens into the central nervous system remain obscure. We report here that Streptococcus pneumoniae (Sp) or polystyrene microspheres, applied to the nose of a mouse, appeared in the meninges of the dorsal cortex within minutes. Recovery of viable bacteria from dissected tissue and fluorescence microscopy showed that up to at least 72h, Sp and microspheres were predominantly in the outer of the two meninges, the pachymeninx. No Sp were found in blood or cerebrospinal fluid. Evidence that this was not an artifact of the method of administration is that in mice infected by horizontal transmission, Sp were also predominantly in the meninges and absent from blood. Intravital imaging through the skull, and flow cytometry showed recruitment and activation of LysM+ cells in the dorsal pachymeninx at 5h and 10h following intranasal infection. Imaging of the cribriform plate suggested that both Sp and microspheres entered through its foramina via an inward flow of fluid connecting the nose to the pachymeninx. Our findings bring further insight into the invasion mechanisms of bacterial pathogens such as Sp into the central nervous system, but are also pertinent to the delivery of drugs to the brain, and the entry of air-borne particles into the cranium.

Mesoscale Imaging (B12 Configuration) v1

This protocol gives an overview of mesoscale imaging of calcium activity across the dorsal cortex of GCaMP-expressing mice using the setup in B12. It describes the acquisition regime for a single session, which may be done at rest, during visual (or other sensory) stimulation, or during head-restrained behaviour.

Graspability Modulates the Stronger Electroencephalography Signature of Motor Preparation for Real Objects vs. Pictures

The cognitive and neural bases of visual perception are typically studied using pictures rather than real-world stimuli. Unlike pictures, real objects are actionable solids that can be manipulated with the hands. Recent evidence from human brain imaging suggests that neural responses to real objects differ from responses to pictures; however, little is known about the neural mechanisms that drive these differences. Here, we tested whether brain responses to real objects versus pictures are differentially modulated by the “in-the-moment” graspability of the stimulus. In human dorsal cortex, electroencephalography responses show a “real object advantage” in the strength and duration of mu (μ) and low beta (β) rhythm desynchronization—well-known neural signatures of visuomotor action planning. We compared desynchronization for real tools versus closely matched pictures of the same objects, when the stimuli were positioned unoccluded versus behind a large transparent barrier that prevented immediate access to the stimuli. We found that, without the barrier in place, real objects elicited stronger μ and β desynchronization compared to pictures, both during stimulus presentation and after stimulus offset, replicating previous findings. Critically, however, with the barrier in place, this real object advantage was attenuated during the period of stimulus presentation, whereas the amplification in later periods remained. These results suggest that the “real object advantage” is driven initially by immediate actionability, whereas later differences perhaps reflect other, more inherent properties of real objects. The findings showcase how the use of richer multidimensional stimuli can provide a more complete and ecologically valid understanding of object vision.

Distal Radius Fracture with Bone Fragment Protruded into the Radiocarpal Joint: Two Case Reports

Distal radius fractures often involve comminuted fragments of the dorsal cortex of the radius, but bone fragments rarely protrude into the radiocarpal joint. We report two cases of distal radius fracture with bone fragment protrusion into the radiocarpal joint. To the best of our knowledge, there are no English reports of distal radius fracture with bone fragment protrusion into the radiocarpal joint. Despite the rarity of these cases, clinicians should still be mindful of such injuries and not overlook the possibility of presence of bone fragments within the joint. Missed intra-articular fragments may cause pain, limited range of motion, and subsequent osteoarthritis.