Neurons throughout the brain communicate using both single action potentials and discrete clusters of action potentials called spike bursts or complex spikes. Bursts consist of groups of fast Na+ spikes or spikelets, often at precise intervals, which ride atop a strong depolarizing Ca2+ spike. Given the bidirectionality of spike propagation in neurons (into axons and dendrites), spike bursts represent a discrete and powerful """"""""packaged"""""""" signal: a set of high-frequency Na+ spikes for the axon and a biochemically and electrically potent Ca2+ spike for the dendrite. Not surprisingly, bursts have relevance to sensory processing, network computations, learning and memory, enhanced salience of specific signals, and induction of some forms of epilepsy. A major gap in our understanding is in how spike bursts arise in neurons and what controls their generation and properties. Using a brainstem inhibitory interneuron network (cartwheel cells) as a model system, we explore the hypotheses that a) bursts arising in the axon initial segment (AIS) transform in size, shape, and probability as they forward propagate along the axon and backpropagate into the dendrites, b) the AIS is the site for receptor-mediated modulation of bursts, c) spike bursts provide the trigger for a novel circuit-level plasticity. These ideas will be tested using patch-clamp recording combined with two-photon microscopy and uncaging, and a new voltage imaging technique. The results will aid in understanding network function and dysfunction throughout the brain.

Public Health Relevance

This is a proposal to examine the control of electrical burst-like signaling within single neurons, and how that signaling determines the activity of neighboring neurons. The study will have impact on topics as diverse as sensory processing and drug addiction.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-MDCN-B (02))
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Talley, Edmund M
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Oregon Health and Science University
Schools of Medicine
United States
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Irie, Tomohiko; Trussell, Laurence O (2017) Double-Nanodomain Coupling of Calcium Channels, Ryanodine Receptors, and BK Channels Controls the Generation of Burst Firing. Neuron 96:856-870.e4
Tang, Zheng-Quan; Trussell, Laurence O (2017) Serotonergic Modulation of Sensory Representation in a Central Multisensory Circuit Is Pathway Specific. Cell Rep 20:1844-1854
Lu, Hsin-Wei; Balmer, Timothy S; Romero, Gabriel E et al. (2017) Slow AMPAR Synaptic Transmission Is Determined by Stargazin and Glutamate Transporters. Neuron 96:73-80.e4
Lu, Hsin-Wei; Trussell, Laurence O (2016) Spontaneous Activity Defines Effective Convergence Ratios in an Inhibitory Circuit. J Neurosci 36:3268-80
Balmer, Timothy S; Trussell, Laurence O (2016) Quantum Disentanglement: Electrical Analysis of the Complex Roles of Ions in Filling Vesicles with Glutamate. Neuron 90:667-9
Borges-Merjane, Carolina; Trussell, Laurence O (2015) ON and OFF unipolar brush cells transform multisensory inputs to the auditory system. Neuron 85:1029-42
Tang, Zheng-Quan; Trussell, Laurence O (2015) Serotonergic regulation of excitability of principal cells of the dorsal cochlear nucleus. J Neurosci 35:4540-51
Apostolides, Pierre F; Trussell, Laurence O (2014) Chemical synaptic transmission onto superficial stellate cells of the mouse dorsal cochlear nucleus. J Neurophysiol 111:1812-22
Huang, Hai; Trussell, Laurence O (2014) Presynaptic HCN channels regulate vesicular glutamate transport. Neuron 84:340-6
Apostolides, Pierre F; Trussell, Laurence O (2014) Superficial stellate cells of the dorsal cochlear nucleus. Front Neural Circuits 8:63

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