Profile

Don B. Arnold

Professor

Molecular & Computational Biology
College of Letters Arts & Sciences

Don B. Arnold

Research Topics

  • Cellular Neurobiology
  • Membranes & Transport

Research Images

Fig. 1 (A) Live neuron in dissociated culture expressing intrabodies against PSD95 (green) and Gephyrin (red), which provide a real time map of synaptic inputs. PSD95 intrabody in dendrite of pyramidal cell in slice culture (B) or in dendrite of pyramidal cell in 45 day old mouse (C) that had been in utero electroporated.
Fig. 1 (A) Live neuron in dissociated culture expressing intrabodies against PSD95 (green) and Gephyrin (red), which provide a real time map of synaptic inputs. PSD95 intrabody in dendrite of pyramidal cell in slice culture (B) or in dendrite of pyramidal cell in 45 day old mouse (C) that had been in utero electroporated.
Fig. 2 (A) Schematic of ablating intrabody. (B) Neuron transfected with Gephyrin Intrabody-FRB and FKBP-E3 ligase domain. (C, D) 5 hours after addition of IRAP virtually 100% of endogenous Gephyrin is eliminated. Note that most, if not all, visible puncta in (C) and (D) are from untransfected cells.
Fig. 2 (A) Schematic of ablating intrabody. (B) Neuron transfected with Gephyrin Intrabody-FRB and FKBP-E3 ligase domain. (C, D) 5 hours after addition of IRAP virtually 100% of endogenous Gephyrin is eliminated. Note that most, if not all, visible puncta in (C) and (D) are from untransfected cells.

Research Overview

Modifying the network of synaptic connections between neurons is thought to be the main mechanism for storing information in the brain. We are currently using novel technology, developed in the Arnold lab, to visualize and ablate synaptic connections in living organisms, allowing us to examine how the brain encodes information. We have developed novel recombinant probes known as intrabodies (or FingRs), which label synaptic proteins with very high fidelity and without causing off-target effects. These probes can also be used to ablate their target proteins, leading to functional elimination of synapses in a fast, efficient and specific manner. We have also made FingRs against cytoplasmic proteins such as kinesin.

We are currently using synaptic FingRs to examine the changes in connectivity that occur during learning in larval zebrafish. Using light sheet microscopy we image large portions of the zebrafish brain including the medial pallium, the zebrafish homolog of the amygdala, before and after the fish undergo a modified classical conditioning paradigm. We have found that dramatic rearrangements of synapses take place during this learning and are characterizing the changes. In the future we are interested in examining what happens to the synaptic rearrangements that we see following extinction, or after the zebrafish forgets the learned behavior.

We have recently put together a 2-photon system that allows us to image mice in vivo. Using AAV injections of FingR proteins we can examine excitatory and inhibitory synapses in genetically determined cells in the mouse cortex. We are currently using this paradigm to characterize excitatory/inhibitory ratios of different cell types at different stages of development. Ultimately we are interested in looking at how this balance can be upset in models for diseases such as autism and schizophrenia.

Contact Information

Mailing Address 2910 UPC
Office Location RRI 204B
Office Phone (213) 821-1266
Lab Location RRI. Rm 208
Lab Phone (213) 821-1818
Fax (213) 821-1818
Office Location RRI 204B

Websites

Education

  • B.A.Sc. University of Toronto, 1986.
  • Ph.D. John Hopkins University, 1992.
  • Postdoctoral Fellow, Rockefeller University 1992-1997.
  • Postdoctoral Fellow, Harvard University 1997-1999.

Selected Publications

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  • Al-Bassam, S., Xu, M., Wandless, T.J., and Arnold, D. B. Differential trafficking of transport vesicles contributes to localization of dendritic proteins. in press Cell Reports.
  • Lewis, T.L. Jr., Mao, T, and Arnold, D. B. (2011) A role for Myosin VI in localization of axonal proteins. PLoS Biology e1001021. PMID:21390300 PubMed Link
  • Arnold DB. (2009) Actin and microtubule-based cytoskeletal cues direct polarized targeting of proteins in neurons. Science Signaling, 2(83):pe49. PubMed
  • Lewis TL Jr, Mao T, Svoboda K, Arnold DB. (2009) Myosin-dependent targeting of transmembrane proteins to neuronal dendrites. Nat Neurosci.12(5):568-576. PubMed
  • Chu PJ, Rivera JF, Arnold DB. (2006) A role for Kif17 in transport of Kv4.2. J Biol Chem. 281(1):365-373. PubMed
  • Arnold DB. (2007) Polarized targeting of ion channels in neurons. Pflugers Arch. 453(6):763-769. PubMed
  • Rivera, J. F., Ahmad, S., Quick, M. W., Liman, E. R., and Arnold, D. B. (2003) An evolutionarily conserved dileucine motif in Shal K+ channels mediates dendritic targeting. Nat Neurosci. 6(3):243-250. PubMed
  • Arnold DB. (1999) Clapham DE Molecular determinants for subcellular localization of PSD-95 with an interacting K+ channel. Neuron 23(1):149-157. PubMed
  • Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME. (1998) Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20(4):709-726. PubMed
  • Arnold DB, Heintz N. (1997) A calcium responsive element that regulates expression of two calcium binding proteins in Purkinje cells. Proc Natl Acad Sci USA 94(16):8842-8847. PubMed