Patrick O. Kanold

Bio: Patrick O. Kanold is an academic researcher from Johns Hopkins University. The author has contributed to research in topics: Auditory cortex & Sensory system. The author has an hindex of 35, co-authored 97 publications receiving 4524 citations. Previous affiliations of Patrick O. Kanold include Harvard University & Johns Hopkins University School of Medicine.

The Subplate and Early Cortical Circuits

Abstract: The developing mammalian cerebral cortex contains a distinct class of cells, subplate neurons (SPns), that play an important role during early development. SPns are the first neurons to be generated in the cerebral cortex, they reside in the cortical white matter, and they are the first to mature physiologically. SPns receive thalamic and neuromodulatory inputs and project into the developing cortical plate, mostly to layer 4. Thus SPns form one of the first functional cortical circuits and are required to relay early oscillatory activity into the developing cortical plate. Pathophysiological impairment or removal of SPns profoundly affects functional cortical development. SPn removal in visual cortex prevents the maturation of thalamocortical synapses, the maturation of inhibition in layer 4, the development of orientation selective responses and the formation of ocular dominance columns. SPn removal also alters ocular dominance plasticity during the critical period. Therefore, SPns are a key regulator of cortical development and plasticity. SPns are vulnerable to injury during prenatal stages and might provide a crucial link between brain injury in development and later cognitive malfunction.

PirB Restricts Ocular-Dominance Plasticity in Visual Cortex

Abstract: Experience can alter synaptic connectivity throughout life, but the degree of plasticity present at each age is regulated by mechanisms that remain largely unknown. Here, we demonstrate that Paired-immunoglobulin-like receptor B (PirB), a major histocompatibility complex class I (MHCI) receptor, is expressed in subsets of neurons throughout the brain. Neuronal PirB protein is associated with synapses and forms complexes with the phosphatases Shp-1 and Shp-2. Soluble PirB fusion protein binds to cortical neurons in an MHCI-dependent manner. In mutant mice lacking functional PirB, cortical ocular-dominance plasticity is more robust at all ages. Thus, an MHCI receptor is expressed in central nervous system neurons and functions to limit the extent of experience-dependent plasticity in the visual cortex throughout life. PirB is also expressed in many other regions of the central nervous system, suggesting that it may function broadly to stabilize neural circuits.

Role of Subplate Neurons in Functional Maturation of Visual Cortical Columns

Abstract: The subplate forms a transient circuit required for development of connections between the thalamus and the cerebral cortex. When subplate neurons are ablated, ocular dominance columns do not form in the visual cortex despite the robust presence of thalamic axons in layer 4. We show that subplate ablation also prevents formation of orientation columns. Visual responses are weak and poorly tuned to orientation. Furthermore, thalamocortical synaptic transmission fails to strengthen, whereas intracortical synapses are unaffected. Thus, subplate circuits are essential not only for the anatomical segregation of thalamic inputs but also for key steps in synaptic remodeling and maturation needed to establish the functional architecture of visual cortex.

Multiple periods of functional ocular dominance plasticity in mouse visual cortex

Abstract: The precise period when experience shapes neural circuits in the mouse visual system is unknown. We used Arc induction to monitor the functional pattern of ipsilateral eye representation in cortex during normal development and after visual deprivation. After monocular deprivation during the critical period, Arc induction reflects ocular dominance (OD) shifts within the binocular zone. Arc induction also reports faithfully expected OD shifts in cat. Shifts towards the open eye and weakening of the deprived eye were seen in layer 4 after the critical period ends and also before it begins. These shifts include an unexpected spatial expansion of Arc induction into the monocular zone. However, this plasticity is not present in adult layer 6. Thus, functionally assessed OD can be altered in cortex by ocular imbalances substantially earlier and far later than expected.

Dichotomy of functional organization in the mouse auditory cortex

Abstract: The sensory areas of the cerebral cortex possess multiple topographic representations of sensory dimensions. Gradient of frequency selectivity (tonotopy) is the dominant organizational feature in the primary auditory cortex, while other feature-based organizations are less well established. We probed the topographic organization of the mouse auditory cortex at the single cell level using in vivo two-photon Ca2+ imaging. Tonotopy was present on a large scale but was fractured on a fine scale. Intensity tuning, important in level-invariant representation, was observed in individual cells but was not topographically organized. The presence or near-absence of putative sub-threshold responses revealed a dichotomy in topographic organization. Inclusion of sub-threshold responses revealed a topographic clustering of neurons with similar response properties, while such clustering was absent in supra-threshold responses. This dichotomy indicates that groups of nearby neurons with locally shared inputs can perform independent parallel computations in ACX.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Ultrasensitive fluorescent proteins for imaging neuronal activity.

Abstract: Fluorescent calcium sensors are widely used to image neural activity. Using structure-based mutagenesis and neuron-based screening, we developed a family of ultrasensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies and mice in vivo. In layer 2/3 pyramidal neurons of the mouse visual cortex, GCaMP6 reliably detected single action potentials in neuronal somata and orientation-tuned synaptic calcium transients in individual dendritic spines. The orientation tuning of structurally persistent spines was largely stable over timescales of weeks. Orientation tuning averaged across spine populations predicted the tuning of their parent cell. Although the somata of GABAergic neurons showed little orientation tuning, their dendrites included highly tuned dendritic segments (5-40-µm long). GCaMP6 sensors thus provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.

Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances

Abstract: Brain injury in premature infants is of enormous public health importance because of the large number of such infants who survive with serious neurodevelopmental disability, including major cognitive deficits and motor disability. This type of brain injury is generally thought to consist primarily of periventricular leukomalacia (PVL), a distinctive form of cerebral white matter injury. Important new work shows that PVL is frequently accompanied by neuronal/axonal disease, affecting the cerebral white matter, thalamus, basal ganglia, cerebral cortex, brain stem, and cerebellum. This constellation of PVL and neuronal/axonal disease is sufficiently distinctive to be termed "encephalopathy of prematurity". The thesis of this Review is that the encephalopathy of prematurity is a complex amalgam of primary destructive disease and secondary maturational and trophic disturbances. This Review integrates the fascinating confluence of new insights into both brain injury and brain development during the human premature period.

Complement and microglia mediate early synapse loss in Alzheimer mouse models

Abstract: Synapse loss in Alzheimer’s disease (AD) correlates with cognitive decline. Involvement of microglia and complement in AD has been attributed to neuroinflammation, prominent late in disease. Here we show in mouse models that complement and microglia mediate synaptic loss early in AD. C1q, the initiating protein of the classical complement cascade, is increased and associated with synapses before overt plaque deposition. Inhibition of C1q, C3, or the microglial complement receptor CR3 reduces the number of phagocytic microglia, as well as the extent of early synapse loss. C1q is necessary for the toxic effects of soluble β-amyloid (Aβ) oligomers on synapses and hippocampal long-term potentiation. Finally, microglia in adult brains engulf synaptic material in a CR3-dependent process when exposed to soluble Aβ oligomers. Together, these findings suggest that the complement-dependent pathway and microglia that prune excess synapses in development are inappropriately activated and mediate synapse loss in AD.