Publications by authors named "Darrick Lo"

The medial prefrontal cortex (MPF) regulates autonomic and neuroendocrine responses to stress and coordinates goal-directed behaviours such as attention, decision-making and social interactions. However, the underlying mechanisms remain unclear due to incomplete circuit-level MPF characterization. Here, using integrated neuroanatomical, physiological and behavioural approaches, we construct a comprehensive wiring diagram of the MPF, focused on the dorsal peduncular area (DP)-a poorly understood prefrontal area.

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Currently, classification of neuron types in the mouse thalamus remains largely incomplete. The anterior thalamic nuclei (ATN), a Papez circuit component, encompass the anterodorsal (AD), anteroventral (AV), and anteromedial (AM) thalamic nuclei. Structurally, the ATN facilitate communication among the neocortex, hippocampus, amygdala, and hypothalamus.

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The medial prefrontal cortex (MPF) regulates emotions, stress responses, and goal-directed behaviors like attention and decision-making. However, the precise mechanisms underlying MPF function remain poorly understood, largely due to an incomplete characterization of its neural circuitry. Leveraging neuroanatomical, neurophysiological, and behavioral techniques, we present a detailed wiring diagram of the MPF, with a particular focus on the dorsal peduncular area (DP), an underexplored MPF area implicated in psychological stress, fear conditioning, anxiety, depression, and opioid addiction.

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The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative.

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An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization.

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The superior colliculus (SC) receives diverse and robust cortical inputs to drive a range of cognitive and sensorimotor behaviors. However, it remains unclear how descending cortical input arising from higher-order associative areas coordinate with SC sensorimotor networks to influence its outputs. Here, we construct a comprehensive map of all cortico-tectal projections and identify four collicular zones with differential cortical inputs: medial (SC.

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The basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted.

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Finite element (FE) models are frequently used to assess mechanical interactions between orthopedic implants and surrounding bone. However, FE studies are often limited by the small number of bones that are modeled; the use of normal bones that do not reflect the altered bone density distributions that result from osteoarthritis (OA); and the application of simplified load cases usually based on peak forces and without consideration of tibiofemoral kinematics. To overcome these limitations, we undertook an integrated approach to determine the most critical scenario for the interaction between an uncemented tibial component and surrounding proximal tibial bone.

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Understanding the organization of the hippocampus is fundamental to understanding brain function related to learning, memory, emotions, and diseases such as Alzheimer's disease. Physiological studies in humans and rodents have suggested that there is both structural and functional heterogeneity along the longitudinal axis of the hippocampus. However, the recent discovery of discrete gene expression domains in the mouse hippocampus has provided the opportunity to re-evaluate hippocampal connectivity.

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Cerebral amyloid angiopathy (CAA), in which amyloid accumulates predominantly in the walls of arterioles and capillaries, is seen in most patients with Alzheimer disease (AD) and may contribute to compromise of blood-brain barrier (BBB) function seen in AD. We investigated the effects of CAA on BBB integrity by examining the expression of the endothelial marker CD31, basement membrane protein collagen IV (COL4), tight junction protein claudin-5, and fibrinogen, a marker of BBB leakage, by immunohistochemistry in the occipital cortex of autopsy brains with AD and capillary CAA (CAA type 1; n = 8), AD with noncapillary CAA (CAA type 2; n = 10), and AD without CAA (n = 7) compared with elderly controls (n = 10). Given the difference in pathogenesis of capillary and noncapillary CAA, we hypothesize that features of BBB breakdown are observed only in capillary CAA.

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Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD) and 7 cognitively normal (NC) subjects. Brains were scanned post-mortem at 7 Tesla.

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Objective: The pathologic validation of European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP).

Methods: Temporal lobes of nine Alzheimer's disease (AD) and seven cognitively normal subjects were scanned post-mortem at 7 Tesla. Hippocampal volumes were obtained with HarP.

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Purpose: Total and reverse total shoulder arthroplasty (TSA) are used to treat patients with glenohumeral joint osteoarthritis. The revision rate remains high compared with hip and knee arthroplasty. Glenoid component loosening is an important complication and may be caused by poor positioning of the component.

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Background: Navigation allows for determination of the mechanical axis of the lower extremity during high tibial osteotomy (HTO) procedures. The objectives of this study were to (1) evaluate the reliability of noninvasive registration with an image-free navigation system for HTO and (2) determine the accuracy of the navigation system to monitor changes in lower limb alignment as compared with alignment measured with a novel 3-dimensional computed tomography method.

Hypothesis: Navigated limb alignment demonstrates good reliability and accuracy in all 3 planes.

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