Training-Included Potentiation in the Neocortex and its Interaction with Stimulation-Induced Long-Term Potentiation and Long-Term Depression

Abstract

<p>Long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy following high-frequency electrical stimulation. Long-term depression (LTD) is a low-frequency stimulation induced reduction in synaptic efficacy. LTP-inducing stimulation is delivered pre-synaptically through an electrode which has been lowered into a neural pathway in an animal's brain. The stimulation parameters used to induce LTP produce alterations which have many of the same properties as memory. As such, LTP is a popular laboratory model of learning and memory. However, the relationship between LTP and memory remains unclear. The fundamental problem associated with linking the two phenomena is that the experimental paradigms used to study them are fundamentally different. Memory is typically measured behaviorally; LTP is typically assessed by measuring the size of evoked potentials -- an indication of synaptic efficacy. New methods allow the relationship to be more closely examined. The best of these paradigms involves training animals on a atask which requires them to encode information, then monitoring for changes which resemble LTP in the regions of the brain associated with the aquired skill. Collectively this approach is known as behavioral LTP. These paradigms have had limited success, because it is difficult to isolate a memory trace in the brain and rule out confounding variables which may be responsible for any recorded changes. In this thesis a behavioral paradigm is employed which requires animals to reach with one limb to retrieve a food reward. This reaching task paradigm is more effective in dealing with these problems then those used in the past. Because the task is unilateral, the animals can serve as their own controls, eliminating some confounds of previous experiments (such as stress level). The cortical region, which encodes the information necessary to aquire the skill, is relatively circumscrived compared to other tasks and structures. In the current experiments, animals unilaterally trained on the reaching task had larger evoked potentials in the trained hemisphere relative to the untrained hemisphere. Furthermore, subsequent LTP induction was reduced in the trained hemisphere compared to the trained hemisphere. These results are consistent with the hypothesis that LTP and memory have the same underlying mechanism (the training-induced potentiation is believed to "use up" some of the modifiability of the affected synapses). Also consistent with this hypothesis is the finding that either long-term depression LTD- or LTP-inducing stimulation delivered following the acquisition of the task disrupted memory storage. Collectively these data support both the conclusion that memories are stored as synaptic changes and that the reaching task paradigm is a useful tool for investigating the relationship between LTP and memory.</p>