About the Work in Our Laboratory...

Knowing the dimensions and connectivity of synapses is fundamental to understanding function. In the brain, more than 90% of synapses occur on dendritic spines. These tiny protrusions from the surface of dendrites measure about 1 micrometer in length. Dendritic spine structure is clearly important for normal brain function because when brain function is impaired, such as in conditions of mental retardation, epilepsy, and stroke, the dendritic spines are either gone, or have highly distorted shapes and sizes.

We integrate fluorescent laser microscopy (figure) with 3D reconstruction and analysis from serial electron microscopy to investigate the structure of dendritic spines and their synapses. These methods allow us to assess the structural basis of synaptic function using multiple approaches. For example, we have determined that long-term potentiation (LTP) matures 2-3 weeks after birth in the rat at about the same time when dendritic spines begin to form in the hippocampus, a brain region involved in certain forms of learning and memory. These findings suggest that the spines are needed for hippocampal neurons to express LTP. In the mature brain, more dendritic spines and synapses form when synaptic activity is reduced or blocked. This finding suggests that spine formation is homeostatically regulated by global activity levels. More spines form when a neuron receives insufficient levels of activation. The new spine synapses can then be incorporated into new networks to support new memories.

Future goals are to develop animal models and add molecular biological tools to these structural and physiological approaches to investigate the synaptic basis of learning and memory.

Selected publications:

Harris KM, Teyler TJ. (1984) Developmental onset of long-term potentiation in area CA1 of the rat hippocampus. J. Physiol., 346:27-48.

Jackson PS, Suppes T, Harris KM (1993) Stereotypical changes in the pattern and duration of long-term potentiation at postnatal days 11 and 15 in the rat hippocampus. J.Neurophysiol. 70:1412-1419.

Harris KM and Kater, S. (1994) Dendritic spines: Cellular specializations that impart stability and flexibility to synaptic function. Ann. Rev. Neurosci. 17:341-371.

Sorra KE, and Harris, KM (1998) Stability in synapse number and size at two hours after long-term potentiation in hippocampal area CA1. J. Neuroscience 18(2):658-671. (1406K PDF)

Fiala, JC, Feinberg, M. Popov, V. and Harris, KM (1998) Synaptogenesis via dendritic filopodia in developing hippocampal area CA1. J. Neuroscience 18:8900-8911. (1,182K PDF)

Kirov, SA, Sorra, KE, Harris, KM (1999) Slices have more synapses than perfusion-fixed hippocampus from both young and mature rats. J. Neuroscience 19:2876-2886. (1,426K PDF)

Ventura R, and Harris KM (1999) Three-Dimensional Relationships between Hippocampal Synapses and Astrocytes J. Neurosci. 19:6897-6906. (888K PDF)

Kirov SA and Harris KM (1999) Dendrites are more spiny on mature hippocampal neurons when synapses are inactivated. Nat Neurosci 2(10):878-883 (643K PDF)

Harris, KM (1999) Structure, Development, and Plasticity of Dendritic Spines. Current Opinion in Neurobiology 9:343-348. (669K PDF)