Alberto E. Pereda, M.D., Ph.D.
Our laboratory is interested in the properties and dynamics of gap junction-mediated electrical transmission in the vertebrate brain. Because perhaps of the relative simplicity of transmission, electrical synapses are generally perceived as passive intercellular channels that lack dynamic control. While the study of plasticity of chemical synapses has long been an area of primary interest to neuroscientists, less is known about the modifiability of electrical synapses.
We investigate these dynamic properties in both mammalian and teleost (goldfish and larval zebrafish) electrical synapses. In contrast with mammalian electrical synapses that generally have limited experimental access, lower vertebrates have provided with advantageous experimental models in which basic properties of electrical transmission can be more easily study. This is the case of identifiable auditory afferents terminating on teleost Mauthner cells known as “Large Myelinated Club endings”. These endings are “mixed” (electrical and chemical) synaptic contacts that offer the rare opportunity to correlate physiological properties with molecular composition and specific ultrastructural features of individual synapses. Gap junctions at these model synapses undergo activity-dependent potentiation and are mediated by fish homologs of connexin 36, which is widely distributed across the mammalian brain.
Our current work focuses on the mechanisms underlying activity-dependent changes in electrical synapses by investigating:
- Their functional relationship with glutamate receptors.
- Their interaction with the dopaminergic and endocannabinoid systems.
- The molecular mechanisms responsible for changes in the strength of electrical transmission, in particular the role of trafficking of gap junction channels and interactions with connexin-associated regulatory proteins.
- Interactions between intrinsic membrane properties and gap junctional conductance, as a mechanism for the control of the synaptic strength.
Thus, while focusing in the properties of electrical synapses, the research of our laboratory explores the complexity of synaptic transmission and signaling mechanisms in general.
- Pereda A. (2014) Electrical synapses and their interactions with chemical synapses. Nature Reviews Neuroscience 15:250-263.
- Rash J.E., Curti S., Davidson K.G.V., Nannapaneni S., Palacios-Prado N., Flores C., Yasumura T., O'Brien J., Bukauskas F., Nagy J.I. and Pereda A. (2013) Molecular and functional asymmetry at a vertebrate electrical synapse. Neuron 79:957-969.
- Pereda A., Schweizer F.E. and Zottoli S.J. (2013) On the training of future neuroscientists: insights from the Grass Laboratory. Neuron 79:12-15.
- Palacios-Prado N., Hoge, G., Marandykina A., Rimkute L., Chapuis S., Paulauskas N., Skeberdis V., O'Brien J., Pereda A., Bennett M.V.L. and Bukauskas F. (2013) Intracellular magnesium-dependent modulation of gap junction channels formed by neuronal connexin36. The Journal of Neuroscience 33:4741-4753.
- Curti S., Hoge G., Nagy J.I. and Pereda A. (2012) Synergy between electrical coupling and membrane properties promotes strong synchronization of neurons of the mesencephalic trigeminal nucleus. The Journal of Neuroscience 32:4341-4359.
- Flores C., Nannapaneni S., Davidson K., Yasumura T., Bennett, M.V.L., Rash J.R. and Pereda A. (2012) Trafficking of gap junction channels at a vertebrate electrical synapse in vivo. Proceedings of the National Academy of Sciences (USA) 109:E573-582.
- Hoge G., Davidson K., Yasumura T., Castillo P., Rash J.R. and Pereda A. (2011) The extent and strength of electrical coupling between inferior olivary neurons is heterogeneous. Journal of Neurophysiology 105:1089-1101.
- Flores C., Cachope R., Nannapaneni S., Ene S., Nairn A. and Pereda A. (2010) Variability of distribution of Ca++/calmodulin-dependent kinase II at mixed synapses on the Mauthner cell: co-localization and association with connexin 35. The Journal of Neuroscience 30:9488-9499.
- Flores C., Li X., Bennett M.V.L., Nagy J.I., and Pereda A. (2008) Interaction between connexin 35 and zonula occludens 1 and its potential role in regulation of electrical synapses. Proceedings of the National Academy of Sciences (USA) 105:12545–12550.
- Cachope R., Mackie K., Triller A., O’Brien J. and Pereda A. (2007) Potentiation of electrical and glutamatergic synaptic transmission mediated by endocannabinoids. Neuron 56:1034-1047.
- Curti S. and Pereda A. (2004) Voltage-dependent enhancement of electrical coupling by a sub-threshold sodium current. The Journal of Neuroscience 24:3999-4010.
- Smith M. and Pereda A. (2003) Chemical synaptic activity modulates nearby electrical synapses. Proceedings of the National Academy of Sciences (USA) 100:4849-4854.
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