Alberto Pereda

Properties and plasticity of electrical synapses

Our laboratory is interested in the properties and dynamics of gap junction-mediated electrical transmission in the vertebrate brain. Perhaps because of the relative simplicity of transmission, electrical synapses are generally perceived as passive intercellular channels that lack dynamic control. Thus, 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.

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 connexin35, the fish ortholog of connexin36 which is widely distributed across the mammalian brain.

Our current work focuses on the mechanisms underlying activity-dependent changes in gap junction-mediated electrical synapses by investigating:

• Their functional relationship with glutamate receptors in both fish and mammals.
• Their interaction with dopaminergic and endocannabinoid systems.
• The molecular mechanisms responsible for changes in electrical transmission, in particular the identification of connexin-associated regulatory proteins.
• The interaction between membrane and synaptic properties, 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.

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.

Curti S. Gomez L., Budelli R. and. and Pereda A. (2008) Subthreshold sodium current underlies essential functional specializations at primary auditory afferents. Journal of Neurophysiology 99:1683-99.

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.

Pereda A., J. O’Brien, J.I. Nagy, F. Bukauskas, K.G.V. Davidson, N. Kamasawa, T. Yasumura, and Rash J. E. (2003) Connexin 35 mediates electrical transmission at mixed synapses on Mauthner cells. The Journal of Neuroscience 23:7489-503.

Smith, M., and Pereda, A. (2003) Chemical synaptic activity modulates nearby electrical synapses. Proceedings of the National Academy of Sciences (USA) 100:4849-4854.

Pereda, A., Bell, T., Chang B., Czernik, A., Nairn, A., Soderling, T., and Faber D.S. (1998) Ca²⁺/calmodulin-dependent kinase II mediates simultaneous enhancement of gap junctional conductance and glutamatergic transmission. Proceedings of the National Academy of Sciences (USA) 95:13272-13277.