Biomedical subjects

Gayle M Wittenberg

Publications and source records attributed to Gayle M Wittenberg.

5 recordsLinked to original sources

PubMed2006

Malleability of spike-timing-dependent plasticity at the CA3-CA1 synapse.

The magnitude and direction of synaptic plasticity can be determined by the precise timing of presynaptic and postsynaptic action potentials on a millisecond timescale. In vivo, however, neural activity has structure on longer timescales. Here we show that plasticity at the CA3-CA1 synapse depends strongly on parameters other than millisecond spike timing. As a result, the notion that a single spike-timing-dependent plasticity (STDP) rule alone can fully describe the mapping between neural activity and synapse strength is invalid. We have begun to explore the influence of additional behaviorally relevant activity parameters on STDP and found conditions under which underlying spike-timing-dependent rules for potentiation and depression can be separated from one another. Potentiation requires postsynaptic burst firing at 5 Hz or higher, a firing pattern that occurs during the theta rhythm. Potentiation is measurable after only tens of presynaptic-before-postsynaptic pairings. Depression requires hundreds of pairings but has less stringent long timescale requirements and broad timing dependence. By varying these parameters, we obtain STDP curves that are long-term potentiation only, bidirectional, or long-term depression only. This expanded description of the CA3-CA1 learning rule reconciles apparent contradictions between spike-timing-dependent plasticity and previous work at CA3-CA1 synapses.

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PubMed2005

Graded bidirectional synaptic plasticity is composed of switch-like unitary events.

Biological information storage events are often rapid transitions between discrete states. In neural systems, the initiation of bidirectional plasticity by all-or-none events may help confer robustness on memory storage. Here, we report that at CA3-CA1 hippocampal synapses, individual potentiation and depression plasticity events are discrete and heterogeneous in nature. Individual synapses began from extreme high and low strength states. Unitary plasticity events were all-or-none and drove synaptic strength between extremes in <1 min. Under naïve conditions, approximately three-fourths of synapses began in a low-strength state. The timing of these unitary events can account for the time course of macroscopic synaptic plasticity.

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PubMed2005

Dissection of bidirectional synaptic plasticity into saturable unidirectional processes.

In populations of synapses, overall synaptic strength can undergo either a net strengthening (long-term potentiation) or weakening (long-term depression). These phenomena have distinct induction pathways, but the functional outcome is usually measured as a single lumped quantity. In hippocampal CA3-CA1 synapses, we took two approaches to study the activity dependence of each phenomenon in isolation. First, we selectively blocked one process by applying kinase or phosphatase inhibitors known, respectively, to block potentiation or depression. Second, we saturated depression or potentiation and examined the activity dependence of the converse process. The resulting unidirectional learning rules could be recombined to give a well-known bidirectional frequency-dependent learning rule under the assumption that when both pathways are activated kinases dominate, resulting in potentiation. Saturation experiments revealed an additional process in which potentiated synapses can be locked at high strength. Saturability of the components of plasticity implies that the amount of plasticity contributed by each pathway depends on the initial level of strength of the synapses. Variation in the distribution of initial synaptic strengths predicts a form of metaplasticity and can account for differences in learning rules observed under several physiological and genetic manipulations.

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PubMed2002

Synaptic reentry reinforcement based network model for long-term memory consolidation.

The conversion of newly formed declarative memories into long-term memories is known to be dependent on the hippocampus. Recent experiments suggest that memory consolidation requires reactivation of the NMDA receptor in CA1 during the initial week(s) after training. This led to the hypothesis that the repeated post-learning reinforcement of synaptic modifications, termed synaptic reentry reinforcement (SRR), is essential for long-term memory consolidation and storage. Based on experimental observations, we have built a computational model to further illustrate and explore the effect of the SRR process on the formation of long-term memory. We show that SRR is capable of strengthening and maintaining memory traces despite inherent variability in the system due to such processes as the turnover of synaptic receptors and their associated signaling and structural proteins. Furthermore, we demonstrate that new rounds of synaptic modification triggered by memory reactivation, either during conscious recall or sleep, could lead to the selective consolidation of a subset of memory traces. Finally, we show why the SRR process in the hippocampus is required during the initial post-training weeks for synaptic reinforcement based memory consolidation in the cortex.

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PubMed2002

An emerging molecular and cellular framework for memory processing by the hippocampus.

The hippocampus plays a central role in memory consolidation, a process for converting short-term memory into cortically stored, long-lasting memory in the mammalian brain. Here, we review recent data and discuss the 'synaptic re-entry reinforcement' (SRR) hypothesis, which can account for the role of the hippocampus in memory consolidation at both the molecular and systems levels. The central idea of the SRR hypothesis is that reactivation of neural ensembles in the hippocampus during the consolidation period results in multiple rounds of NMDA-receptor-dependent synaptic reinforcement of the hippocampal memory traces created during initial learning. In addition, such reactivation and reinforcement processes permit the hippocampus to act as a 'coincidence regenerator', providing coordinated input that drives the coherent reactivation of cortical neurons, resulting in the progressive strengthening of cortical memory traces through reactivation of cortical NMDA receptors.

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