Our laboratory is interested in structural and functional synaptic plasticity in the adult brain. We are investigating the relationship between changes in synaptic connectivity and training- or experience-dependent adaptations in cortical network function. We image cortical neurons in fluorescent transgenic mice in vivo, using high-resolution two-photon laser scanning microscopy through chronic cranial window implants. We track individual dendritic spines and axonal boutons, which are the structural proxies for synapses, over weeks to months while the animal receives new sensory experiences or loses sensory inputs. In addition, we measure the molecular stability and dynamics of individual synapses by monitoring the transport and diffusion of synaptic proteins carrying a fluorescent tag. Functional changes are measured using optical imaging of activity-related intrinsic signals and whole cell or LFP recordings in vivo. Together these studies will deepen our understanding of how the nervous system adapts to changes in sensory inputs and accommodates the animal’s memory storage while the overall integrity of the neuronal network is preserved.

Gambino, F., Holtmaat, A. (2012) Spike-timing dependent potentiation of sensory surround in the somatosensory cortex is facilitated by deprivation-mediated disinhibition. Neuron. In Press

Wilbrecht, L., Holtmaat, A., Wright, N., Fox, K., Svoboda, K. (2010) Structural plasticity underlies experience-dependent functional plasticity of cortical circuits. J. Neurosci. 30: 4927-4932.

Holtmaat, A., Svoboda, K. (2009) Experience-dependent structural synaptic plasticity in the mam- malian brain. Nature Rev. Neurosci. 10: 647-658.

Holtmaat, A. et al. (2009) Long-term, high resolution imaging in the mouse neocortex through a chronic cranial window. Nature Protoc. 4: 1128-144.

Knott, G., Holtmaat, A., Wilbrecht, L., Welker, E., Svoboda, K. (2006) Spine growth precedes synapse formation in the adult neocortex in vivo. Nature Neurosci. 9: 1117-1124.

Holtmaat, A., Wilbrecht, L., Knott, G., Welker, E., Svoboda, K. (2006) Experience-dependent and cell- type specific spine growth in the neocortex. Nature 441: 979-983.

De Paola, V., Holtmaat, A., Knott, G., Song, S., Wilbrecht, L., Caroni, P., Svoboda, K. (2006) Cell type- specific structural plasticity of axonal branches and boutons in the adult neocortex. Neuron 49:861-875. 979-983.

In vivo two-photon laser scanning microscopy

Intrinsic optical imaging

In vivo electrophysiolgy

Transgenic mice and viral vectors

Molecular neurobiology