Abstract
Sleep is important for learning and consolidation of memories. It is believed that sleep’s influence over synaptic plasticity is a core part of this function, but the exact mechanisms underlying this process remain mysterious. An influential but controversial idea proposes that while animals are awake, actively engaging with their environment and forming memories, neural plasticity is dominated by LTP-like processes that lead to a net strengthening of synapses. If left unopposed, this would saturate synapses, and so the hypothesis asserts that a crucial function of sleep is to drive widespread downscaling of excitatory synaptic strengths to homeostatically compensate. In this thesis, I present work that used real-time sleep classification, ex vivo measurements of postsynaptic strength, and in vivo optogenetic monitoring of thalamocortical synaptic efficacy to ask whether sleep and wake states can constitutively drive changes in synaptic strength within the neocortex of juvenile rats. We found that miniature EPSC amplitudes onto L4 and L2/3 pyramidal neurons were stable across sleep and wake dense epochs in both primary visual (V1) and prefrontal cortex (PFC). Further, chronic monitoring of thalamocortical synaptic efficacy in V1 of freely behaving animals revealed stable responses across even prolonged periods of natural sleep and wake. Together these data demonstrate that sleep does not drive widespread downscaling of synaptic strengths during the highly plastic critical period in juvenile animals. Whether this remarkable stability across sleep and wake generalizes to the fully mature nervous system remains to be seen. In summary, this thesis work attempts to reconcile competing ideas over how sleep and other brain states might modulate synaptic plasticity to stabilize and promote learning and memory.