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Abstract
Persistent synaptic plasticity has been subjected to intense study in the decades since it was first described. Occurring in the form of long-term potentiation (LTP) and long-term depression (LTD), it shares many cellular and molecular properties with hippocampus-dependent forms of persistent memory. Recent reports of both LTP and LTD occurring endogenously under specific learning conditions provide further support that these forms of synaptic plasticity may comprise the cellular correlates of memory. Most studies of synaptic plasticity are performed using in vitro or in vivo preparations where patterned electrical stimulation of afferent fibers is implemented to induce changes in synaptic strength. This strategy has proven very effective in inducing LTP, even under in vivo conditions. LTD in vivo has proven more elusive: although LTD occurs endogenously under specific learning conditions in both rats and mice, its induction has not been successfully demonstrated with afferent electrical stimulation alone. In this study we screened a large spectrum of protocols that are known to induce LTD either in hippocampal slices or in the intact rat hippocampus, to clarify if LTD can be induced by sole afferent stimulation in the mouse CA1 region in vivo. Low frequency stimulation at 1, 2, 3, 5, 7, or 10 Hz given in the range of 100 through 1800 pulses produced, at best, short-term depression (STD) that lasted for up to 60 min. Varying the administration pattern of the stimuli (e.g., 900 pulses given twice at 5 min intervals), or changing the stimulation intensity did not improve the persistency of synaptic depression. LTD that lasts for at least 24 h occurs under learning conditions in mice. We conclude that a coincidence of factors, such as afferent activity together with neuromodulatory inputs, play a decisive role in the enablement of LTD under more naturalistic (e.g., learning) conditions.
Highlights
Synaptic plasticity describes the ability of neurons to modify the strength or efficacy of their signal transmission across synapses
In this study we screened a large spectrum of protocols that are known to induce long-term depression (LTD) either in hippocampal slices or in the intact rat hippocampus, to clarify if LTD can be induced by sole afferent stimulation in the mouse CA1 region in vivo
LTD that lasts for days and weeks has been described in this species (Abraham et al, 1994; Heynen et al, 1996; Manahan-Vaughan and Braunewell, 1999)
Summary
Synaptic plasticity describes the ability of neurons to modify the strength or efficacy of their signal transmission across synapses. Patterned stimulation of afferent fibers to the hippocampus can induce persistent changes in synaptic transmission that is capable of lasting for hours or days and even up to weeks (Bliss and Lomo, 1973; Abraham et al, 1994; Abraham, 2003). Relevant information is believed to be stored through long-lasting changes in synaptic strength across the synapses in the neural circuits involved in the encoding process This process can be mimicked by electrical stimulation of afferent fibers to the hippocampus, whereby LTP is typically elicited via application of a short and brief stimulation (e.g., 0.5 s, 1 s) at high frequencies (e.g., 50 Hz, 100 Hz), and is often dependent on the activation of the ionotropic N-methyl-D-aspartate (NMDA) glutamate receptors (Bliss and Collingridge, 1993; Huang et al., 1996). The activation of the NMDA receptors, like in LTP, is known to be crucial for the induction of LTD in the hippocampus CA1 region (Dudek and Bear, 1992; Heynen et al, 1996)
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