Diane Lipscombe
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View article: Control of Synaptic Communication through Molecularly Engineered Bioluminescence Light Emission and Sensing
Control of Synaptic Communication through Molecularly Engineered Bioluminescence Light Emission and Sensing Open
Synapses are sites of intercellular communication between neurons and from neurons to target organs, and of signal integration that underly physiological and behavioral responses. We have developed a modular platform, Interluminescence (In…
View article: <i>Trpv1</i> -dependent <i>Cacna1b</i> gene inactivation reveals cell-specific functions of Ca<sub>V</sub>2.2 channels <i>in vivo</i>
<i>Trpv1</i> -dependent <i>Cacna1b</i> gene inactivation reveals cell-specific functions of Ca<sub>V</sub>2.2 channels <i>in vivo</i> Open
Voltage-gated Ca V 2.2 channels underlie the N-type current, and they regulate calcium entry at many presynaptic nerve endings to control transmitter release. A role for Ca V 2.2 channels has been well-established in the transmission of pa…
View article: Peripheral Ca <sub>V</sub> 2.2 Channels in the Skin Regulate Prolonged Heat Hypersensitivity during Neuroinflammation
Peripheral Ca <sub>V</sub> 2.2 Channels in the Skin Regulate Prolonged Heat Hypersensitivity during Neuroinflammation Open
Neuroinflammation can lead to chronic maladaptive pain affecting millions of people worldwide. Neurotransmitters, cytokines, and ion channels are implicated in neuroimmune cell signaling, but their roles in specific behavioral responses ar…
View article: Peripheral Ca<sub>V</sub>2.2 channels in skin regulate prolonged heat hypersensitivity during neuroinflammation
Peripheral Ca<sub>V</sub>2.2 channels in skin regulate prolonged heat hypersensitivity during neuroinflammation Open
Neuroinflammation can lead to chronic maladaptive pain affecting millions of people worldwide. Neurotransmitters, cytokines, and ion channels are implicated in neuro-immune cell signaling but their roles in specific behavioral responses ar…
View article: Engineering luminopsins with improved coupling efficiencies
Engineering luminopsins with improved coupling efficiencies Open
Whole cell patch clamp recordings allowed us to quantify the impact of different characteristics of LMOs on their function. Our results suggest that coupling brighter bioluminescent sources to more sensitive opsins will improve LMO functio…
View article: Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence
Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence Open
We report a robust new option for achieving multiple modes of control in a single actuator and a promising engineering strategy for continued improvement of BL-OG.
View article: Towards a Brighter Constellation: Multi-Organ Neuroimaging of Neural and Vascular Dynamics in the Spinal Cord and Brain
Towards a Brighter Constellation: Multi-Organ Neuroimaging of Neural and Vascular Dynamics in the Spinal Cord and Brain Open
Significance Pain is comprised of a complex interaction between motor action and somatosensation that is dependent on dynamic interactions between the brain and spinal cord. This makes understanding pain particularly challenging as it invo…
View article: Interleukin-1α links peripheral Ca<sub>V</sub>2.2 channel activation to rapid adaptive increases in heat sensitivity in skin
Interleukin-1α links peripheral Ca<sub>V</sub>2.2 channel activation to rapid adaptive increases in heat sensitivity in skin Open
Neurons have the unique capacity to adapt output in response to changes in their environment. Within seconds, sensory nerve endings can become hypersensitive to stimuli in response to potentially damaging events. The underlying behavioral …
View article: Engineering luminopsins with improved coupling efficiencies
Engineering luminopsins with improved coupling efficiencies Open
Significance Luminopsins (LMOs) are bioluminescent-optogenetic tools with a luciferase fused to an opsin that allow bimodal control of neurons by providing both optogenetic and chemogenetic access. Determining which design features contrib…
View article: ω-Phonetoxins inhibit voltage-gated calcium Ca<sub>V</sub>2.2 ion channel splice isoforms of dorsal root ganglia
ω-Phonetoxins inhibit voltage-gated calcium Ca<sub>V</sub>2.2 ion channel splice isoforms of dorsal root ganglia Open
Cell-specific alternative splicing of Cacna1b pre-mRNA generates functionally distinct voltage-gated Ca V 2.2 channels. Ca V 2.2 channels mediate the release of glutamate from nociceptor termini in the dorsal horn spinal cord and they are …
View article: A Bioluminescent Activity Dependent (BLADe) Platform for Converting Intracellular Activity to Photoreceptor Activation
A Bioluminescent Activity Dependent (BLADe) Platform for Converting Intracellular Activity to Photoreceptor Activation Open
Genetically encoded sensors and actuators have advanced the ability to observe and manipulate cellular activity, yet few non-invasive strategies enable cells to directly couple their intracellular states to user-defined outputs. We develop…
View article: A New Highly Efficient Molecule for Both Optogenetic and Chemogenetic Control Driven by FRET Amplification of BioLuminescence
A New Highly Efficient Molecule for Both Optogenetic and Chemogenetic Control Driven by FRET Amplification of BioLuminescence Open
Significance Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO). Aim To further enhance the utility o…
View article: CaBLAM! A high-contrast bioluminescent Ca<sup>2+</sup> indicator derived from an engineered <i>Oplophorus gracilirostris</i> luciferase
CaBLAM! A high-contrast bioluminescent Ca<sup>2+</sup> indicator derived from an engineered <i>Oplophorus gracilirostris</i> luciferase Open
Measuring ongoing cellular activity is essential to understanding the dynamic functions of biological organisms. The most popular current approach is imaging fluorescence-based genetically encoded Ca 2+ indicators (GECIs). While fluorescen…
View article: Up-regulation of cholesterol synthesis pathways and limited neurodegeneration in a knock-in<i>Sod1</i>mutant mouse model of ALS
Up-regulation of cholesterol synthesis pathways and limited neurodegeneration in a knock-in<i>Sod1</i>mutant mouse model of ALS Open
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder affecting brain and spinal cord motor neurons. Mutations in the copper/zinc superoxide dismutase gene ( SOD1 ) are associated with ∼20% of inherited and 1-2% of spo…
View article: Analysing an allelic series of rare missense variants of <i>CACNA1I</i> in a Swedish schizophrenia cohort
Analysing an allelic series of rare missense variants of <i>CACNA1I</i> in a Swedish schizophrenia cohort Open
CACNA1I is implicated in the susceptibility to schizophrenia by large-scale genetic association studies of single nucleotide polymorphisms. However, the channelopathy of CACNA1I in schizophrenia is unknown. CACNA1I encodes CaV3.3, a neuron…
View article: Selective Control of Synaptically-Connected Circuit Elements by All-Optical Synapses
Selective Control of Synaptically-Connected Circuit Elements by All-Optical Synapses Open
Understanding percepts, engrams and actions requires methods for selectively modulating synaptic communication between specific subsets of interconnected cells. Here, we develop an approach to control synaptically connected elements using …
View article: Heat But Not Mechanical Hypersensitivity Depends on Voltage-Gated Ca<sub>V</sub>2.2 Calcium Channel Activity in Peripheral Axon Terminals Innervating Skin
Heat But Not Mechanical Hypersensitivity Depends on Voltage-Gated Ca<sub>V</sub>2.2 Calcium Channel Activity in Peripheral Axon Terminals Innervating Skin Open
Voltage-gated CaV2.2 calcium channels are expressed in nociceptors at presynaptic terminals, soma, and axons. CaV2.2 channel inhibitors applied to the spinal cord relieve pain in humans and rodents, especially during pathologic pain, but a…
View article: Bioluminescent optogenetic (BL-OG) activation of neurons during mouse postnatal brain development
Bioluminescent optogenetic (BL-OG) activation of neurons during mouse postnatal brain development Open
Bioluminescent optogenetics (BL-OG) allows activation of photosensory proteins, such as opsins, by either fiberoptics or by administering a luciferin. BL-OG thus confers both optogenetic and chemogenetic access within the same genetically …
View article: Epigenetic control of ion channel expression and cell-specific splicing in nociceptors: Chronic pain mechanisms and potential therapeutic targets
Epigenetic control of ion channel expression and cell-specific splicing in nociceptors: Chronic pain mechanisms and potential therapeutic targets Open
Ion channels underlie all forms for electrical signaling including the transmission of information about harmful events. Voltage-gated calcium ion channels have dual function, they support electrical signaling as well as intracellular calc…
View article: Peripheral voltage-gated calcium channels in skin are essential for transient neurogenic thermal hyperalgesia in mice
Peripheral voltage-gated calcium channels in skin are essential for transient neurogenic thermal hyperalgesia in mice Open
Voltage-gated Ca V 2.2 calcium channels are expressed in nociceptors, at pre-synaptic terminals, soma, and axons. Ca V 2.2 channel inhibitors applied to the spinal cord relieve pain in humans and rodents, especially during pathological pai…
View article: Miniaturized Devices for Bioluminescence Imaging in Freely Behaving Animals
Miniaturized Devices for Bioluminescence Imaging in Freely Behaving Animals Open
In vivo fluorescence miniature microscopy has recently proven a major advance, enabling cellular imaging in freely behaving animals. However, fluorescence imaging suffers from autofluorescence, phototoxicity, photobleaching and non- homoge…
View article: Miniaturized Devices for Bioluminescence Imaging in Freely Behaving Animals
Miniaturized Devices for Bioluminescence Imaging in Freely Behaving Animals Open
Fluorescence miniature microscopy in vivo has recently proven a major advance, enabling cellular imaging in freely behaving animals. However, fluorescence imaging suffers from autofluorescence, phototoxicity, photobleaching and non-homogen…
View article: Cell-specific exon methylation and CTCF binding in neurons regulate calcium ion channel splicing and function
Cell-specific exon methylation and CTCF binding in neurons regulate calcium ion channel splicing and function Open
Cell-specific alternative splicing modulates myriad cell functions and is disrupted in disease. The mechanisms governing alternative splicing are known for relatively few genes and typically focus on RNA splicing factors. In sensory neuron…
View article: Framework for advancing rigorous research
Framework for advancing rigorous research Open
There is a pressing need to increase the rigor of research in the life and biomedical sciences. To address this issue, we propose that communities of 'rigor champions' be established to campaign for reforms of the research culture that has…
View article: Cell-specific exon methylation and CTCF binding in neurons regulates calcium ion channel splicing and function
Cell-specific exon methylation and CTCF binding in neurons regulates calcium ion channel splicing and function Open
Summary Cell-specific alternative splicing modulates myriad cell functions and this process is disrupted in disease. The mechanisms governing alternative splicing are known for relatively few genes and typically focus on RNA splicing facto…
View article: Cacna1b alternative splicing impacts excitatory neurotransmission and is linked to behavioral responses to aversive stimuli
Cacna1b alternative splicing impacts excitatory neurotransmission and is linked to behavioral responses to aversive stimuli Open
Presynaptic Ca V 2.2 channels control calcium entry that triggers neurotransmitter release at both central and peripheral synapses. The Cacna1b gene encodes the α1-pore forming subunit of Ca V 2.2 channels. Distinct subsets of splice varia…