REGULATION OF SYNAPTIC AMINO ACID RECEPTORS

Summary

Principal Investigator: Laurence O Trussell
Abstract: Inhibitory interneurons are essential to shaping the output of neuronal circuits. Different circuits perform different computations, and so it follows that the way in which inhibition is expressed and regulated varies accordingly. In feedforward inhibition, the interneuron and the principal cell it contacts are activated by the same afferent fibers, and thus the principal cell experiences inhibition following a brief excitation However, this inhibition also acts on other, unrelated excitatory inputs to the cell. This principle forms the basis for circuits that integrate information across sensory modalities, in which signals from one modality can gate on and off the passage of information from another. This proposal focuses on control of inhibitory neurons in the gating of signals in the dorsal cochlear nucleus (DCN), a cerebellar-like structure unique to mammals. The DCN is believed to play a key role in orientation toward significant sounds. DCN fusiform neurons receive input from auditory nerve and from a system of parallel fibers carrying multimodal input, including proprioceptive signals encoding the position of the head and ears. DCN parallel fibers also activate inhibitory glycinergic cartwheel cells, which provide feedforward inhibition to fusiform cells capable of virtually shutting down auditory signals to higher regions. This relatively simple circuit, and the unusual properties of synapses made by parallel fibers and cartwheel cells, provide an opportunity to understand how sensory signals may be gated in the mammalian brain. We will investigate how cartwheel cells contribute to this function through the kinetics and plasticity of their synaptic contacts. Patch-clamp techniques will be combined with imaging methods and photolysis-based mapping methods to identify circuits formed by cartwheel cells, and work out mechanisms and function of short term plasticity mediated by endocannabinoid signaling, and a novel spike-timing dependent long-term plasticity. The results will provide new information regarding the function of this and related circuits. Moreover, this work may lend new clues to the treatment of tinnitus, a condition thought to be maintained by long-term plasticity in this brain region.
Funding Period: ----------------1991 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi Ion channels generating complex spikes in cartwheel cells of the dorsal cochlear nucleus
    Yuil Kim
    Oregon Hearing Research Center Vollum Institute, Mail Code L 335A, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    J Neurophysiol 97:1705-25. 2007
  2. ncbi The physiology of the axon initial segment
    Kevin J Bender
    Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA
    Annu Rev Neurosci 35:249-65. 2012
  3. pmc Two-photon compatibility and single-voxel, single-trial detection of subthreshold neuronal activity by a two-component optical voltage sensor
    Ann E Fink
    Unit of Dynamic Neuronal Imaging, Department of Neuroscience, Paris, France
    PLoS ONE 7:e41434. 2012
  4. pmc Axon initial segment Ca2+ channels influence action potential generation and timing
    Kevin J Bender
    Vollum Institute and Oregon Hearing Research Center, Oregon Health and Science University, Portland, OR 97239, USA
    Neuron 61:259-71. 2009
  5. pmc Fidelity of complex spike-mediated synaptic transmission between inhibitory interneurons
    Michael T Roberts
    Vollum Institute and Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Neurosci 28:9440-50. 2008
  6. pmc Coactivation of pre- and postsynaptic signaling mechanisms determines cell-specific spike-timing-dependent plasticity
    Thanos Tzounopoulos
    Department of Cell Biology and Anatomy, Rosalind Franklin University, Chicago Medical School, North Chicago, IL 60064, USA
    Neuron 54:291-301. 2007
  7. ncbi Synaptic inputs to granule cells of the dorsal cochlear nucleus
    Veeramuthu Balakrishnan
    Oregon Hearing Research Center and Vollum Institute, L335A, 3181 S W Sam Jackson Park Rd, Portland, OR 97239, USA
    J Neurophysiol 99:208-19. 2008
  8. pmc Control of firing patterns through modulation of axon initial segment T-type calcium channels
    Kevin J Bender
    Oregon Hearing Research Centre and Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
    J Physiol 590:109-18. 2012
  9. pmc KCNQ5 channels control resting properties and release probability of a synapse
    Hai Huang
    Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon, USA
    Nat Neurosci 14:840-7. 2011
  10. pmc Synaptic plasticity in inhibitory neurons of the auditory brainstem
    Kevin J Bender
    Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, 3181 S W Sam Jackson Park Road, L335A, Portland, OR 97239, USA
    Neuropharmacology 60:774-9. 2011

Scientific Experts

  • Kevin J Bender
  • Hai Huang
  • Laurence O Trussell
  • Michael T Roberts
  • Veeramuthu Balakrishnan
  • Yuil Kim
  • Ann E Fink
  • Thanos Tzounopoulos
  • Thomas S Otis
  • David A DiGregorio
  • Sidney P Kuo
  • Patrick D Roberts
  • John E Keen
  • Maria E Rubio

Detail Information

Publications14

  1. ncbi Ion channels generating complex spikes in cartwheel cells of the dorsal cochlear nucleus
    Yuil Kim
    Oregon Hearing Research Center Vollum Institute, Mail Code L 335A, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    J Neurophysiol 97:1705-25. 2007
    ..Thus the diverse electrical behavior of cartwheel cells is determined by the interaction of a wide variety of ion channels with a prominent role played by Ca(2+)...
  2. ncbi The physiology of the axon initial segment
    Kevin J Bender
    Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA
    Annu Rev Neurosci 35:249-65. 2012
    ..Thus, the AIS is not merely the beginning of the axon, but rather a key site in the control of neuronal excitability...
  3. pmc Two-photon compatibility and single-voxel, single-trial detection of subthreshold neuronal activity by a two-component optical voltage sensor
    Ann E Fink
    Unit of Dynamic Neuronal Imaging, Department of Neuroscience, Paris, France
    PLoS ONE 7:e41434. 2012
    ....
  4. pmc Axon initial segment Ca2+ channels influence action potential generation and timing
    Kevin J Bender
    Vollum Institute and Oregon Hearing Research Center, Oregon Health and Science University, Portland, OR 97239, USA
    Neuron 61:259-71. 2009
    ..Similar results were found in cortex and cerebellum. Thus, voltage-gated Ca(2+) channels at the site of spike initiation play a key role in generating and shaping spike bursts...
  5. pmc Fidelity of complex spike-mediated synaptic transmission between inhibitory interneurons
    Michael T Roberts
    Vollum Institute and Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Neurosci 28:9440-50. 2008
    ..We suggest that rapid transmission of complex spikes may control the susceptibility of neighboring neurons to Ca2+-dependent plasticity...
  6. pmc Coactivation of pre- and postsynaptic signaling mechanisms determines cell-specific spike-timing-dependent plasticity
    Thanos Tzounopoulos
    Department of Cell Biology and Anatomy, Rosalind Franklin University, Chicago Medical School, North Chicago, IL 60064, USA
    Neuron 54:291-301. 2007
    ..Hence, pre- and postsynaptic sites of expression determine both the sign and timing requirements of long-term plasticity in interneurons...
  7. ncbi Synaptic inputs to granule cells of the dorsal cochlear nucleus
    Veeramuthu Balakrishnan
    Oregon Hearing Research Center and Vollum Institute, L335A, 3181 S W Sam Jackson Park Rd, Portland, OR 97239, USA
    J Neurophysiol 99:208-19. 2008
    ..The glycinergic synaptic conductance was mediated by heteromeric glycine receptors and was far stronger than the glutamatergic conductance, suggesting that glycinergic neurons may act to gate nonauditory signals in the DCN...
  8. pmc Control of firing patterns through modulation of axon initial segment T-type calcium channels
    Kevin J Bender
    Oregon Hearing Research Centre and Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
    J Physiol 590:109-18. 2012
    ..Thus, the axon initial segment is a key site, and dopamine a key regulator, of spontaneous bursting activity...
  9. pmc KCNQ5 channels control resting properties and release probability of a synapse
    Hai Huang
    Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon, USA
    Nat Neurosci 14:840-7. 2011
    ..Thus, ion channel determinants of presynaptic resting potential also control synaptic strength...
  10. pmc Synaptic plasticity in inhibitory neurons of the auditory brainstem
    Kevin J Bender
    Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, 3181 S W Sam Jackson Park Road, L335A, Portland, OR 97239, USA
    Neuropharmacology 60:774-9. 2011
    ..This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'...
  11. pmc Dopaminergic modulation of axon initial segment calcium channels regulates action potential initiation
    Kevin J Bender
    Oregon Hearing Research Center, Oregon Health and Science University, Portland, OR 97239, USA
    Neuron 68:500-11. 2010
    ..This pathway represents a new mechanism to inhibit neurons by specifically regulating Ca(2+) channels directly involved in action potential initiation...
  12. pmc Negative shift in the glycine reversal potential mediated by a Ca2+- and pH-dependent mechanism in interneurons
    Yuil Kim
    Neuroscience Graduate Program, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Neurosci 29:11495-510. 2009
    ..Thus, a Ca(2+)-dependent mechanism serves to maintain or enhance the strength of inhibition in the face of increased excitatory activity...
  13. pmc Slow glycinergic transmission mediated by transmitter pooling
    Veeramuthu Balakrishnan
    Oregon Hearing Research Center, 3181 S W Sam Jackson Park Road, Portland, Oregon 97239, USA
    Nat Neurosci 12:286-94. 2009
    ..Thus, temporal properties of inhibition can be controlled by activity levels in multiple presynaptic cells or by adjusting release probability at individual synapses...
  14. pmc Molecular layer inhibitory interneurons provide feedforward and lateral inhibition in the dorsal cochlear nucleus
    Michael T Roberts
    Vollum Institute and Oregon Hearing Research Center, Oregon Health and Science University, Portland, OR 97239, USA
    J Neurophysiol 104:2462-73. 2010
    ..These synaptic relationships suggest that the set of parallel fibers activated by a particular sensory stimulus determines whether cartwheel cells provide feedforward or lateral inhibition to their postsynaptic targets...