Potential for change: Characterizing synaptic plasticity following visual discrimination learning in adult rats.

Abstract

Synaptic plasticity (long-term potentiation, LTP and long-term depression, LTD) plays an important role in processes of learning and memory formation. In order to provide a link between these neurophysiological and cognitive processes the following experiments were performed using behavioral, electrophysiological, and pharmacological in vivo methods in order to describe synaptic plasticity in the adult rat visual system after learning a simple visual discrimination task. Initially, a novel method is described providing a simple and noninvasive means to restrict visual input. Using a harness and face-mask for monocular occlusion, rats were trained in a monocular visual discrimination task using a Y-shaped water maze. Following learning, assessment of synaptic plasticity in the thalamocortical visual pathway found both general (changes in short-term plasticity in both cerebral hemispheres) and localized changes (greater LTP levels in the hemisphere contralateral to the open eye). The enhanced LTP in the primary visual cortex (V1) was blocked by an NR2B antagonist, suggesting that training resulted in changes in NMDA receptor expression or functioning. Next, the effectiveness of LTD stimulation protocols to elicit synaptic depression under in vivo conditions were assessed. Of several single-pulse induction protocols tested, only strong low frequency burst stimulation (SLFS) produced significant, but transient (~20 min) depression in V1 (not affected by blockade of NMDA or metabotrobic glutamate receptors). These data highlight the resistance of the thalamocortical visual system to undergo synaptic depression in vivo. To examine whether learning alters LTD induction, SLFS was delivered to the thalamocortical visual pathway or the V1-perirhinal cortex pathway following visual discrimination. Neither pathway exhibited changes in LTD following training, suggesting that the learning-induced LTP facilitation reflects an expansion of the synaptic modification range. Finally, the role of different populations of NMDA receptors (cortical vs. thalamic) in LTP induction in naïve and visually trained rats was examined. Surprisingly, naïve rats do not require activation of cortical NMDA receptors to express LTP, while LTP in trained rats involved the activation of both thalamic and cortical NMDA receptors. In summary, this thesis provides novel evidence for a metaplastic, training-induced up-regulation of LTP mechanisms in the thalamocortical visual system of adult rats.