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.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01NS028901-25
Application #
8657488
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Talley, Edmund M
Project Start
Project End
Budget Start
Budget End
Support Year
25
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
City
Portland
State
OR
Country
United States
Zip Code
97239
Apostolides, Pierre F; Trussell, Laurence O (2014) Control of interneuron firing by subthreshold synaptic potentials in principal cells of the dorsal cochlear nucleus. Neuron 83:324-30
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
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
Apostolides, Pierre F; Trussell, Laurence O (2013) Rapid, activity-independent turnover of vesicular transmitter content at a mixed glycine/GABA synapse. J Neurosci 33:4768-81
Bender, Kevin J; Uebele, Victor N; Renger, John J et al. (2012) Control of firing patterns through modulation of axon initial segment T-type calcium channels. J Physiol 590:109-18
Huang, Hai; Trussell, Laurence O (2011) KCNQ5 channels control resting properties and release probability of a synapse. Nat Neurosci 14:840-7
Bender, Kevin J; Ford, Christopher P; Trussell, Laurence O (2010) Dopaminergic modulation of axon initial segment calcium channels regulates action potential initiation. Neuron 68:500-11
Bender, Kevin J; Trussell, Laurence O (2009) Axon initial segment Ca2+ channels influence action potential generation and timing. Neuron 61:259-71
Tzounopoulos, Thanos; Kim, Yuil; Oertel, Donata et al. (2004) Cell-specific, spike timing-dependent plasticities in the dorsal cochlear nucleus. Nat Neurosci 7:719-25

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