The laboratory investigates the properties and dynamics of gap junction-mediated electrical transmission in the vertebrate brain. 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 plastic properties of electrical synapses in teleosts (goldfish and zebrafish) and mammals. Lower vertebrates have provided with advantageous experimental models in which basic properties of electrical transmission can be more easily study. Auditory “mixed” (electrical and chemical) synaptic contacts on the teleost Mauthner cells offer the rare opportunity to correlate physiological properties with molecular composition and specific ultrastructural features of individual synapses. Electrical transmission at these terminals undergo activity-dependent potentiation and is mediated by gap junctions formed by fish homologs of connexin 36, a neuronal gap junction protein widely distributed across the mammalian brain. Our current work focuses on the mechanisms underlying activity-dependent changes in electrical synapses by investigating: i) Their functional relationship with glutamate receptors, ii) Their interaction with the dopaminergic and endocannabinoid systems, iii) 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, iv) Interactions between intrinsic membrane properties and gap junctional conductance, as a mechanism for the control of synaptic strength at electrical synapses. 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.

1.   Lasseigne A., Echeverry F., Ijaz S., Michel J., Martin A., Marsh A., Trujillo E., Marsden K., Pereda A., Miller A. (2021) Electrical synaptic transmission requires postsynaptic scaffolding protein, eLife,10:e66898.

2.   Alcamí P. and Pereda A. (2019) Beyond plasticity: the dynamic impact of electrical synapses on neural circuits, Nature Reviews Neuroscience, 20:253-271.

3.   Marsden K.C., Jain R.A., Wolman M., Echeverry F.A., Nelson J.C., Hayer K.E., Miltenberg. B., Pereda A.E., and Granato M. A (2018) Cyfip2-dependent excitatory interneuron pathway establishes the innate startle threshold. Cell Reports, 23:878–887.

4.   Jain R.A., Wolman M.A., Marsden K.C., Nelson J.C., Shoenhard H., Echeverry F.A., Szi C., Bell H., Skinner J., Cobbs E.N., Sawada K., Zamora A., Pereda A.E., Granato M. (2018) A forward genetic screen in zebrafish identifies the G-protein coupled receptor CaSR as a modulator of sensorimotor decision-making. Current Biology, 28:1357–1369.

5.   Cachope R., and Pereda A. (2015) Opioids potentiate electrical synaptic transmission at mixed synapses on the Mauthner cell, Journal of Neurophysiology, 114:689–697.

6.   Yao C., Davidson K., Delfiner M., Eddy V., Lucaci A., Soto-Riveros C., Yasumura T., Rash J.E., Pereda A. (2014) Electrical synaptic transmission in developing zebrafish: properties and molecular composition of gap junctions at a central auditory synapse, Journal of Neurophysiology, 112:2102–2113.

7.   Pereda A. (2014) Electrical synapses and their interactions with chemical synapses. Nature Reviews Neuroscience 15:250–263.

8. 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.

9.  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.

10. 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.

11.  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.