Dynamics of Electrically Coupled Neuronal Networks

Neurons communicate primarily via connections known as electro-chemical synapses, billions of which are in any piece of brain tissue and are essential for its function. However, certain types of neurons also interact via a totally different type of synapse: a direct electrical connection known as a gap-junction. The prevalence of these electrical synapses in the central nervous system is well established, as well as their role in generating synchronized rhythmic network activity. However, a comprehensive understanding of the connections efficacy and their role in setting network dynamics is at the most rudimentary. Here we propose to combine cutting edge experiments and theory in order to perform a thorough characterization of the efficacy and function of electrical synapses in the mammalian brain. The experiments will be done in two important brain structures where electrical synapses exist. In the cerebral cortex, which is responsible for perception, action and high-cognitive functions, inhibitory neurons are coupled via gap junctions. The second brain region is the inferior olive, an important brain structure where neurons rely only on gap junctions to communicate within the structure. We will perform both in vitro and in vivo experiments and will include whole-cell recordings, imaging techniques and optogenetic to address specific subpopulation of neurons. We will develop methodology for estimating the number of electrically coupled neurons; the role of the dendritic passive and active membrane properties and dendritic gap-junction location, on the connection efficacy; and how electro-chemical synapses and gap- junctions interact. At the network level, we will analyze the parameters for rhythmic activity, and examine under what conditions electrically coupled networks operate as a coincident detectors for their inputs. It is expected that at the end of this study, not only will we offer a complete new set of tools to study electrically coupled networks, we will also apply them to unravel the principles of operation of two prominent networks in the mammalian brain.