The Billups Group - Synaptic Mechanisms
The Synaptic Mechanisms Laboratory investigates how individual synapses in the central nervous system function and how they are modulated. These processes ultimately control how information is carried through the brain. We use electrophysiological recording techniques, such as patch-clamping, combined with fluorescent cellular imaging techniques to probe the function of distinct synapses in neuronal circuits.
Synaptic junctions between two neurons are closely associated with processes from neighbouring astrocytes. These glial cells are integral parts the tripartite synapse structure, sensing the activity in the adjacent neurons and releasing compounds that influence the neuronal communication. Our laboratory is particularly interested in how presynaptic terminals release neurotransmitters and how astrocytes regulate this activity.
Many of our studies use the calyx of Held synapse in the auditory brainstem. This synapse is part of the neuronal pathways that integrate sound from the two ears and is involved in the mechanisms that the brain uses to determine the location of a sound. It is a large excitatory (glutamatergic) synapse, with presynaptic, postsynaptic and astrocytic elements that can be easily visually identified and recorded in living tissue. This gives a unique opportunity to study how the different elements of the tripartite synapse contribute to the regulation of neuronal communication.
| Project | Status |
|---|---|
| Glial modulation of neuronal activity | Potential |
| Glutamate recycling at synapses | Potential |
| Regulation of amino acids in the brain | Potential |
Dong, W., Todd, A. C., Broer, A., Hulme, S. R., Broer, S., & Billups, B. (2018). PKC-Mediated Modulation of Astrocyte SNAT3 Glutamine Transporter Function at Synapses in Situ. Int J Mol Sci, 19(4). doi:10.3390/ijms19040924
Todd, A. C., Marx, M. C., Hulme, S. R., Broer, S., & Billups, B. (2017). SNAT3-mediated glutamine transport in perisynaptic astrocytes in situ is regulated by intracellular sodium. Glia, 65(6), 900-916. doi:10.1002/glia.23133
Kirischuk, S., Heja, L., Kardos, J., & Billups, B. (2016). Astrocyte sodium signaling and the regulation of neurotransmission. Glia, 64(10), 1655-1666. doi:10.1002/glia.22943
Marx, M. C., Billups, D., & Billups, B. (2015). Maintaining the presynaptic glutamate supply for excitatory neurotransmission. J Neurosci Res, 93(7), 1031-1044. doi:10.1002/jnr.23561
Burke, L. K., Doslikova, B., D'Agostino, G., Garfield, A. S., Farooq, G., Burdakov, D., … Heisler, L. K. (2014). 5-HT obesity medication efficacy via POMC activation is maintained during aging. Endocrinology, 155(10), 3732-3738. doi:10.1210/en.2014-1223
Billups, D., Marx, M. C., Mela, I., & Billups, B. (2013). Inducible presynaptic glutamine transport supports glutamatergic transmission at the calyx of Held synapse. J Neurosci, 33(44), 17429-17434. doi:10.1523/JNEUROSCI.1466-13.2013
Doslikova, B., Garfield, A. S., Shaw, J., Evans, M. L., Burdakov, D., Billups, B., & Heisler, L. K. (2013). 5-HT2C receptor agonist anorectic efficacy potentiated by 5-HT1B receptor agonist coapplication: an effect mediated via increased proportion of pro-opiomelanocortin neurons activated. J Neurosci, 33(23), 9800-9804. doi:10.1523/JNEUROSCI.4326-12.2013
Uwechue, N. M., Marx, M. C., Chevy, Q., & Billups, B. (2012). Activation of glutamate transport evokes rapid glutamine release from perisynaptic astrocytes. J Physiol, 590(10), 2317-2331. doi:10.1113/jphysiol.2011.226605
Barker, M., Billups, B., & Hamann, M. (2009). Focal macromolecule delivery in neuronal tissue using simultaneous pressure ejection and local electroporation. J Neurosci Methods, 177(2), 273-284. doi:10.1016/j.jneumeth.2008.10.021
Blot, A., Billups, D., Bjorkmo, M., Quazi, A. Z., Uwechue, N. M., Chaudhry, F. A., & Billups, B. (2009). Functional expression of two system A glutamine transporter isoforms in rat auditory brainstem neurons. Neuroscience, 164(3), 998-1008. doi:10.1016/j.neuroscience.2009.09.015
Billups, D., Billups, B., Challiss, R. A., & Nahorski, S. R. (2006). Modulation of Gq-protein-coupled inositol trisphosphate and Ca2+ signaling by the membrane potential. J Neurosci, 26(39), 9983-9995. doi:10.1523/JNEUROSCI.2773-06.2006
Wong, A. Y., Billups, B., Johnston, J., Evans, R. J., & Forsythe, I. D. (2006). Endogenous activation of adenosine A1 receptors, but not P2X receptors, during high-frequency synaptic transmission at the calyx of Held. J Neurophysiol, 95(6), 3336-3342. doi:10.1152/jn.00694.2005
Billups, B. (2005). Colocalization of vesicular glutamate transporters in the rat superior olivary complex. Neurosci Lett, 382(1-2), 66-70. doi:10.1016/j.neulet.2005.02.071
Billups, B., Graham, B. P., Wong, A. Y., & Forsythe, I. D. (2005). Unmasking group III metabotropic glutamate autoreceptor function at excitatory synapses in the rat CNS. J Physiol, 565(Pt 3), 885-896. doi:10.1113/jphysiol.2005.086736
Nash, M. S., Willets, J. M., Billups, B., John Challiss, R. A., & Nahorski, S. R. (2004). Synaptic activity augments muscarinic acetylcholine receptor-stimulated inositol 1,4,5-trisphosphate production to facilitate Ca2+ release in hippocampal neurons. J Biol Chem, 279(47), 49036-49044. doi:10.1074/jbc.M407277200
Dodson, P. D., Billups, B., Rusznak, Z., Szucs, G., Barker, M. C., & Forsythe, I. D. (2003). Presynaptic rat Kv1.2 channels suppress synaptic terminal hyperexcitability following action potential invasion. J Physiol, 550(Pt 1), 27-33. doi:10.1113/jphysiol.2003.046250
Hamann, M., Billups, B., & Forsythe, I. D. (2003). Non-calyceal excitatory inputs mediate low fidelity synaptic transmission in rat auditory brainstem slices. Eur J Neurosci, 18(10), 2899-2902. doi:10.1111/j.1460-9568.2003.03017.x
Wong, A. Y., Graham, B. P., Billups, B., & Forsythe, I. D. (2003). Distinguishing between presynaptic and postsynaptic mechanisms of short-term depression during action potential trains. J Neurosci, 23(12), 4868-4877. doi:10.1523/JNEUROSCI.23-12-04868.2003
Billups, B., Wong, A. Y., & Forsythe, I. D. (2002). Detecting synaptic connections in the medial nucleus of the trapezoid body using calcium imaging. Pflugers Arch, 444(5), 663-669. doi:10.1007/s00424-002-0861-6
Billups, B., & Forsythe, I. D. (2002). Presynaptic mitochondrial calcium sequestration influences transmission at mammalian central synapses. J Neurosci, 22(14), 5840-5847. doi:20026597
Lawrence, C. L., Billups, B., Rodrigo, G. C., & Standen, N. B. (2001). The KATP channel opener diazoxide protects cardiac myocytes during metabolic inhibition without causing mitochondrial depolarization or flavoprotein oxidation. Br J Pharmacol, 134(3), 535-542. doi:10.1038/sj.bjp.0704289
Hack, N. J., Billups, B., Guthrie, P. B., Rogers, J. H., Muir, E. M., Parks, T. N., & Kater, S. B. (2000). Green fluorescent protein as a quantitative tool. J Neurosci Methods, 95(2), 177-184. doi:10.1016/s0165-0270(99)00178-8
Diefenbach, T. J., Guthrie, P. B., Stier, H., Billups, B., & Kater, S. B. (1999). Membrane recycling in the neuronal growth cone revealed by FM1-43 labeling. J Neurosci, 19(21), 9436-9444. doi:10.1523/JNEUROSCI.19-21-09436.1999
Billups, B., Szatkowski, M., Rossi, D., & Attwell, D. (1998). Patch-clamp, ion-sensing, and glutamate-sensing techniques to study glutamate transport in isolated retinal glial cells. Methods Enzymol, 296, 617-632. doi:10.1016/s0076-6879(98)96044-x
Billups, B., Rossi, D., Oshima, T., Warr, O., Takahashi, M., Sarantis, M.,… Attwell, D. (1998). Physiological and pathological operation of glutamate transporters. Prog Brain Res, 116, 45-57. doi:10.1016/s0079-6123(08)60429-x
Spiridon, M., Kamm, D., Billups, B., Mobbs, P., & Attwell, D. (1998). Modulation by zinc of the glutamate transporters in glial cells and cones isolated from the tiger salamander retina. J Physiol, 506 ( Pt 2), 363-376. doi:10.1111/j.1469-7793.1998.363bw.x
Takahashi, M., Billups, B., Rossi, D., Sarantis, M., Hamann, M., & Attwell, D. (1997). The role of glutamate transporters in glutamate homeostasis in the brain. J Exp Biol, 200(Pt 2), 401-409.
Billups, B., Rossi, D., & Attwell, D. (1996). Anion conductance behavior of the glutamate uptake carrier in salamander retinal glial cells. J Neurosci, 16(21), 6722-6731. doi:10.1523/JNEUROSCI.16-21-06722.1996
Billups, B., & Attwell, D. (1996). Modulation of non-vesicular glutamate release by pH. Nature, 379(6561), 171-174. doi:10.1038/379171a0
