Direct electrical connections between neurons are widespread throughout the mammalian brain, but their contribution to brain function is poorly understood. Similar to other types of connections or so-called synapses between neurons, electrical synapses are known to undergo changes in strength. However, the specific conditions that result in plasticity or changes in strength of electrical synapses are unknown. This project investigates the specific neuronal activity rules and underlying mechanisms whereby these synapses are modified by ongoing brain activity. Further, this project aims to advance our understanding of how these activity-dependent modifications of electrical synapse strength impact brain function, in particular that processing of sensory information via the thalamus to the cortex. The findings will yield important new insights into the function of electrical synapses and their plasticity across the brain, and how the brain gates cortical attention to the sensory environment surrounding the organism. The project involves a combination of brain research, undergraduate and graduate training in neuroscience concepts and research techniques, and educational development through special institutional programs aimed at disadvantaged children and youth, with a goal of public education and broadening participation in science, technology, engineering, and mathematics (STEM disciplines) by traditionally underrepresented students.
Learning rules and mechanisms for long-term synaptic modification have been described extensively for neurotransmitter-based synapses. However, strikingly little is yet known about activity-dependent plasticity of electrical synapses, also known as gap junctions. Because electrical synapses are widespread but their importance in mammalian brain function, it is critical that we advance our understanding of whether and how these types of essential synapses are regulated in a use-dependent manner. The central hypothesis of this project is that the strength of electrical synapses in the thalamic reticular nucleus, the major inhibitory regulator of cortico-thalamic communication, is continuously updated by activity in electrically coupled neurons; in turn, this plasticity alters the synchrony within and the inhibitory output of the thalamic reticular nucleus. To test this hypothesis, the control and the impact of electrical synaptic plasticity is investigated using in vitro electrophysiology and optogenetic techniques. Aim 1 examines the mechanisms that underlie plasticity of electrical synapses, with the goal of elucidating and developing predictions about the relationship between activity and synaptic strength. Aim 2 measures the impact of electrical synaptic plasticity on synchrony within networks of coupled thalamic neurons, and thereby offers new insight into the inhibition that coupled interneurons deliver to their downstream targets. Aim 3 tests the functional role of electrical synapse plasticity in brain rhythms and network plasticity. Together, the studies will lead to novel understanding of how electrical synapses contribute to brain function.