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Cellular and Molecular Studies of Synaptic Plasticity
Summary: Erin Schuman is interested in the cellular and molecular mechanisms of synaptic plasticity.
Synapses, the points of contact and communication between neurons, exhibit plasticity: they can vary in their size, strength, and number. This plasticity contributes to the ability to learn and remember. We are interested in how synapses are modified at the cellular and molecular level. We are also interested in how neuronal circuits change when synapses change their properties. We conduct all of our studies in the hippocampus, a structure known to be important for memory in both humans and animals. We use molecular biology, electrophysiology, and fluorescent confocal and two-photon imaging techniques to address our questions.
Activity-Dependent Dynamics and Sequestration of the Proteasome in Dendritic Spines
The regulated degradation of proteins by the ubiquitin proteasome pathway is emerging as an important modulator of synaptic function and plasticity. The proteasome is a large multisubunit cellular machine that recognizes, unfolds, and degrades target polyubiquitinated proteins. We have discovered a striking NMDA receptor–dependent redistribution of the proteasome from dendritic shafts to synaptic spines follows synaptic stimulation, providing a mechanism for local protein degradation.
We used a proteasome activity reporter coupled with local perfusion to show that synaptic stimulation regulates the proteasome activity locally in the dendrites. Restricted photobleaching of individual spines and dendritic shafts revealed the dynamics that underlie the proteasome sequestration: activity modestly enhances the spine entry rate of the proteasome while dramatically reducing the exit rate. The persistent sequestration of the proteasome reflects an enhanced association with the actin-based cytoskeleton. These data indicate that synaptic activity can promote the physical recruitment and sequestration of a major cellular multiprotein machine to remodel the protein composition of synapses locally.
Single-Trial Learning of Novel Stimuli by Individual Neurons of the Human Hippocampus-Amygdala Complex
The ability to distinguish novel from familiar allows nervous systems to rapidly encode the significance of environmental events, following even a single exposure to a stimulus. This detection of novelty is necessary for many types of learning. Neurons in the medial temporal lobe (MTL) are critically involved in the acquisition of long-term declarative memories.
To investigate novelty detection and single-trial learning, we used microwire electrodes implanted in human epilepsy surgery patients to record from individual MTL neurons in vivo. We discovered two classes of neurons in the human hippocampus and amygdala that exhibit single-trial learning by changing their firing patterns in response to a single presentation of a "natural" visual stimuli: (1) novelty detectors increase firing to the first stimulus presentation only and (2) familiarity detectors increase firing for the second stimulus presentation. We find that neurons can show "memory" for the stimulus from 30 minutes to 24 hours after the original stimulus presentation. Thus, neurons in the MTL that are responsible for encoding episodic events contain information sufficient for reliable novelty-familiarity discrimination and also show rapid plasticity as a result of single-trial learning.
Last updated: April 25, 2006
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