Se-Bum Paik

Retinal origin of orientation maps in visual cortex

The orientation map is a hallmark of primary visual cortex in higher mammals. It is not yet known how orientation maps develop, what function they have in visual processing and why some species lack them. Here we advance the notion that quasi-periodic orientation maps are established by moiré interference of regularly spaced ON- and OFF-center retinal ganglion cell mosaics. A key prediction of the theory is that the centers of iso-orientation domains must be arranged in a hexagonal lattice on the cortical surface. Here we show that such a pattern is observed in individuals of four different species: monkeys, cats, tree shrews and ferrets. The proposed mechanism explains how orientation maps can develop without requiring precise patterns of spontaneous activity or molecular guidance. Further, it offers a possible account for the emergence of orientation tuning in single neurons despite the absence of orderly orientation maps in rodents species.

Russell body gastritis associated with Helicobacter pylori infection: a case report

An unusual and rare gastric mucosal lesion histologically consisting of a localised accumulation of Russell bodies and Russell body-containing plasma cells, the so-called Mott cells, has been recognised only recently and termed as “Russell body gastritis”. This lesion, despite its densely monomorphous appearance is easily confirmed to be non-neoplastic by its polyclonal immunoreactive pattern to immunoglobulin light chains. However, the aetiology of Russell body gastritis is controversial and hence the optimal treatment for this disease has not been established. Two cases of Russell body gastritis associated with Helicobacter pylori infection are reported, and the possible role of H pylori infection in the pathogenesis is discussed.

Spontaneous Local Gamma Oscillation Selectively Enhances Neural Network Responsiveness

Synchronized oscillation is very commonly observed in many neuronal systems and might play an important role in the response properties of the system. We have studied how the spontaneous oscillatory activity affects the responsiveness of a neuronal network, using a neural network model of the visual cortex built from Hodgkin-Huxley type excitatory (E-) and inhibitory (I-) neurons. When the isotropic local E-I and I-E synaptic connections were sufficiently strong, the network commonly generated gamma frequency oscillatory firing patterns in response to random feed-forward (FF) input spikes. This spontaneous oscillatory network activity injects a periodic local current that could amplify a weak synaptic input and enhance the networks responsiveness. When E-E connections were added, we found that the strength of oscillation can be modulated by varying the FF input strength without any changes in single neuron properties or interneuron connectivity. The response modulation is proportional to the oscillation strength, which leads to self-regulation such that the cortical network selectively amplifies various FF inputs according to its strength, without requiring any adaptation mechanism. We show that this selective cortical amplification is controlled by E-E cell interactions. We also found that this response amplification is spatially localized, which suggests that the responsiveness modulation may also be spatially selective. This suggests a generalized mechanism by which neural oscillatory activity can enhance the selectivity of a neural network to FF inputs.

Link between orientation and retinotopic maps in primary visual cortex.

Maps representing the preference of neurons for the location and orientation of a stimulus on the visual field are a hallmark of primary visual cortex. It is not yet known how these maps develop and what function they play in visual processing. One hypothesis postulates that orientation maps are initially seeded by the spatial interference of ON- and OFF-center retinal receptive field mosaics. Here we show that such a mechanism predicts a link between the layout of orientation preferences around singularities of different signs and the cardinal axes of the retinotopic map. Moreover, we confirm the predicted relationship holds in tree shrew primary visual cortex. These findings provide additional support for the notion that spatially structured input from the retina may provide a blueprint for the early development of cortical maps and receptive fields. More broadly, it raises the possibility that spatially structured input from the periphery may shape the organization of primary sensory cortex of other modalities as well.

Synaptic Plasticity Controls Sensory Responses through Frequency-Dependent Gamma Oscillation Resonance

Synchronized gamma frequency oscillations in neural networks are thought to be important to sensory information processing, and their effects have been intensively studied. Here we describe a mechanism by which the nervous system can readily control gamma oscillation effects, depending selectively on visual stimuli. Using a model neural network simulation, we found that sensory response in the primary visual cortex is significantly modulated by the resonance between “spontaneous” and “stimulus-driven” oscillations. This gamma resonance can be precisely controlled by the synaptic plasticity of thalamocortical connections, and cortical response is regulated differentially according to the resonance condition. The mechanism produces a selective synchronization between the afferent and downstream neural population. Our simulation results explain experimental observations such as stimulus-dependent synchronization between the thalamus and the cortex at different oscillation frequencies. The model generally shows how sensory information can be selectively routed depending on its frequency components.

Optogenetic Mapping of Functional Connectivity in Freely Moving Mice via Insertable Wrapping Electrode Array Beneath the Skull

Spatiotemporal mapping of neural interactions through electrocorticography (ECoG) is the key to understanding brain functions and disorders. For the entire brain cortical areas, this approach has been challenging, especially in freely moving states, owing to the need for extensive craniotomy. Here, we introduce a flexible microelectrode array system, termed iWEBS, which can be inserted through a small cranial slit and stably wrap onto the curved cortical surface. Using iWEBS, we measured dynamic changes of signals across major cortical domains, namely, somatosensory, motor, visual and retrosplenial areas, in freely moving mice. iWEBS robustly displayed somatosensory evoked potentials (SEPs) in corresponding cortical areas to specific somatosensory stimuli. We also used iWEBS for mapping functional interactions between cortical areas in the propagation of spike-and-wave discharges (SWDs), the neurological marker of absence seizures, triggered by optogenetic inhibition of a specific thalamic nucleus. This demonstrates that iWEBS represents a significant improvement over conventional ECoG recording methodologies and, therefore, is a competitive recording system for mapping wide-range brain connectivity under various behavioral conditions.

BRAF somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors

Pediatric brain tumors are highly associated with epileptic seizures1. However, their epileptogenic mechanisms remain unclear. Here, we show that the oncogenic BRAF somatic mutation p.Val600Glu (V600E) in developing neurons underlies intrinsic epileptogenicity in ganglioglioma, one of the leading causes of intractable epilepsy2. To do so, we developed a mouse model harboring the BRAFV600E somatic mutation during early brain development to reflect the most frequent mutation, as well as the origin and timing thereof. Therein, the BRAFV600E mutation arising in progenitor cells during brain development led to the acquisition of intrinsic epileptogenic properties in neuronal lineage cells, whereas tumorigenic properties were attributed to high proliferation of glial lineage cells. RNA sequencing analysis of patient brain tissues with the mutation revealed that BRAFV600E-induced epileptogenesis is mediated by RE1-silencing transcription factor (REST), which is a regulator of ion channels and neurotransmitter receptors associated with epilepsy. Moreover, we found that seizures in mice were significantly alleviated by an FDA-approved BRAFV600E inhibitor, vemurafenib, as well as various genetic inhibitions of Rest. Accordingly, this study provides direct evidence of a BRAF somatic mutation contributing to the intrinsic epileptogenicity in pediatric brain tumors and suggests that BRAF and REST could be treatment targets for intractable epilepsy.In pediatric brain tumors that are accompanied by epileptic seizures, the BRAF somatic mutation V600E contributes to intrinsic epileptic properties in neurons, which can be suppressed by vemurafenib in mice.

Symmetry of learning rate in synaptic plasticity modulates formation of flexible and stable memories

Spike-timing-dependent plasticity (STDP) is considered critical to learning and memory functions in the human brain. Across various types of synapse, STDP is observed as different profiles of Hebbian and anti-Hebbian learning rules. However, the specific roles of diverse STDP profiles in memory formation still remain elusive. Here, we show that the symmetry of the learning rate profile in STDP is crucial to determining the character of stored memory. Using computer simulations, we found that an asymmetric learning rate generates flexible memory that is volatile and easily overwritten by newly appended information. Moreover, a symmetric learning rate generates stable memory that can coexist with newly appended information. In addition, by combining these two conditions, we could realize a hybrid memory type that operates in a way intermediate between stable and flexible memory. Our results demonstrate that various attributes of memory functions may originate from differences in the synaptic stability.

Sexually dimorphic behavior, neuronal activity, and gene expression in Chd8-mutant mice

Autism spectrum disorders (ASDs) are four times more common in males than in females, but the underlying mechanisms are poorly understood. We characterized sexually dimorphic changes in mice carrying a heterozygous mutation in Chd8 (Chd8+/N2373K) that was first identified in human CHD8 (Asn2373LysfsX2), a strong ASD-risk gene that encodes a chromatin remodeler. Notably, although male mutant mice displayed a range of abnormal behaviors during pup, juvenile, and adult stages, including enhanced mother-seeking ultrasonic vocalization, enhanced attachment to reunited mothers, and isolation-induced self-grooming, their female counterparts do not. This behavioral divergence was associated with sexually dimorphic changes in neuronal activity, synaptic transmission, and transcriptomic profiles. Specifically, female mice displayed suppressed baseline neuronal excitation, enhanced inhibitory synaptic transmission and neuronal firing, and increased expression of genes associated with extracellular vesicles and the extracellular matrix. Our results suggest that a human CHD8 mutation leads to sexually dimorphic changes ranging from transcription to behavior in mice.Autism is ~4 times more common in males. Jung et al. reveal male-preponderant abnormal behaviors in mice lacking CHD8, a chromatin remodeler, accompanying sexually dimorphic changes in neuronal firing, synaptic transmission, and gene expression.

Universality of the developmental origins of diverse functional maps in the visual cortex

The primary visual cortex of higher mammals is organized into diverse functional maps of correlated topography, implying an efficient tiling of functional domains. However, no fundamental principle is available on how systematic organization of the maps could develop initially in various species. Here, we propose that diverse functional maps are seeded from a common framework of retinal afferents, and that this universality of development explains the observed topographical correlations among the maps. From the simulation of retinal ganglion cell mosaics, we successfully developed all four cortical maps observed so far. We validated our model prediction of inter-map relationships from analysis of map data in evolutionarily divergent mammalian species. Our key prediction, the hexagonal periodicity of every functional map, was validated from analysis of the map data in diverse mammalian species. Our results provide new insight into a universal mechanism for the development and evolution of the visual cortex.