Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle

Autor: Gabriella Dias, Adriano B. L. Tort, Ana M. G. Guerreiro, Sidarta Ribeiro, César Rennó-Costa, Catia M. Pereira, Wilfredo Blanco, Sharlene Santos, Adrião Duarte Dória Neto, Vinícius Rosa Cota, Annie C. Souza
Rok vydání: 2015
Předmět:
Zdroj: PLoS Computational Biology
PLoS Computational Biology, Vol 11, Iss 5, p e1004241 (2015)
ISSN: 1553-7358
Popis: Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic restructuring.
Author Summary Sleep is important for long lasting memories. There exists, however, a controversy regarding the mechanisms by which sleep modifies synapses to consolidate enduring memories. One theory posits that sleep weakens synapses, leading to the forgetting of all but the strongest memories. The alternative theory proposes that sleep promotes both weakening and strengthening of different connections, the latter through a process known as long-term potentiation (LTP). Here we measured the levels of a phosphorylated protein related to LTP during the sleep cycle of rats and used the data to build models of sleep-dependent synaptic plasticity. By feeding one model with spikes recorded from the rat hippocampus, we observed that LTP during sleep not merely strengthens certain connections, but actually reorganizes how these connections are ranked in strength, leading to substantial changes of the overall pattern. A more detailed model of hippocampus and cortex showed that the interaction of the mechanisms predicted by the competing theories promotes a more efficient control of which memories are stored. Our results provide a step forward in the understanding of the cognitive role of sleep by indicating that the current competing theories are not mutually exclusive. Instead, each constitutes an important stage of memory consolidation.
Databáze: OpenAIRE
Externí odkaz: