Numerous insights into the sensorimotor systems that guide the control of voice have been garnered by observing how the system responds to manipulations of its auditory feedback. However, current approaches may be limited in the exploration of more complex parameters of volitional and adaptive voice control due to their limited...
Sensorimotor integration is a general term to describe how task-specific motor output is generated from the selective and rapid processing of sensory and motor information. The rodent vibrissal (whisker) system is an important model for the study of sensorimotor integration and active tactile sensing. This research uses the rodent vibrissal...
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by motor neuron (MN) degeneration and resulting in progressive paralysis and death. ALS is genetically heterogeneous, disease pathophysiology is not completely understood, and there are no effective drug therapies. To develop broadly applicable therapeutics, we examine disease mechanisms in the...
Movement is achieved by combining synaptic inputs from various sources and activating motor unit populations. Motor units are the quantal elements of motor control which act as a neuromechanical transducer that converts sensory inputs into motor output. Because of the tight neuromuscular junctions between motoneuron axon terminals and a large...
Mitochondria-lysosome contacts are recently identified sites for mediating crosstalk between both organelles, but their role in normal and diseased human neurons remains unknown. We used super-resolution and live-cell microscopy in human iPSC-derived neurons to demonstrate that mitochondria-lysosome contacts can dynamically form in the soma, axons, and dendrites of human neurons,...
Coordinated movement relies on the precise and controlled activation of populations of motor units, which convert the commands of the nervous system into muscle forces. Motor unit firing patterns are often nonlinear and generated through the response to a combination of ionotropic excitatory and inhibitory commands, as well as metabotropic...
Processing of sensory information in the brain is a pervasive and fundamental phenomenon across animal species and is involved in both "hard-wired" innate responses as well as learned and adaptive behaviors. Here, I show that the avoidance of hot temperature, a simple innate behavior, contains unexpected plasticity and complex processing...
Inter-organelle contact sites have become increasingly appreciated as important regulators of cellular homeostasis, and disruption of inter-organelle contact site dynamics and function has been observed in various pathologies. Recently, inter-organelle contact sites between mitochondria and lysosomes were discovered, offering a new mechanism by which these two organelles may directly interact,...
Chemokines, such as Stromal Derived Factor 1 (SDF-1 or CXCL12) and their G protein coupled receptors (GPCRs) are well known regulators of the development and functions of numerous tissues. CXCL12 has two receptors: CXCR4 and CXCR7 or atypical chemokine receptor 3 (ACKR3). CXCR7 has been described as an atypical “biased”...
We present a biophysical model of GCaMP6f calcium fluorescence in CA1 pyramidal neuron dendrites based upon results from imaging and electrophysiology experiments. This work was completed using experimental results from the laboratory of Professor Daniel Dombeck, Department of Neurobiology. Constraining the model to reproduce different objectives --- from in-vitro and...