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.