Current Research

Karel Svoboda's lab is searching for the substrates of experience-dependent plasticity in the developing and adult neocortex. The functional properties of the brain must change in response to salient sensory experiences, but the nature of these changes at the level of synapses, neurons, and their networks (also known as the engram) is unknown.

Most of the cognitive functions in mammals, ranging from perception to memory formation, are performed in the neocortex, a massive network of neurons. Neurons are linked into circuits by synapses, which pass information between neurons. How do the circuits and synaptic mechanisms underlying this awesome neural network produce our perception of the world? How “plastic” are these neural circuits, that is, how do the physical properties of the neural network change in response to experience? The answers to these questions will profoundly change our understanding of the function and diseases of the brain.

Cortical tissue is dauntingly complex. Each module of cortical tissue (~1 mm3 of gray matter) contains nearly a million neurons, each of which connects to thousands of other neurons. To observe neurons and synapses in the intact brain, we build and use sensitive tools. Two-photon laser scanning microscopy (2PLSM) allows us to image single synapses in intact tissues and to track changes in intracellular calcium and signal transduction events. Excitation of neuronal elements by focal uncaging of neurotransmitters allows us to probe the structure of cortical circuits efficiently. We combine these optical methods with electrophysiological measurements of synaptic currents and potentials and molecular manipulations of neurons.