A Short-term Optogenetically-induced Slow Wave Sleep Improves Memory

Memory is the process in which information is encoded,stored and retrieved.Previous studies have shown that sleep plays an important role in each step of memory.However,due to technical limitation,prior research carried out mainly through the induction of sleep(human)or sleep deprivation(SD)(human or animal),leading to either indirect or mixed results because of stress induced by sleep deprivation that impaires the formation of memory.Thus previous studies could not dissect the effect of sleep on memory formation completely.Recent studies have indicated that the parafacial zone of medulla(PZ)may promot sleep,therefore,we manipulated PZ GABA neurons optogenetically for specific regulation of sleep.The vesicular GABA transporter(VGAT)is the membrane protein that updates inhibitory neurotransmitter GABA into vesicles and is usually used as a marker of GABA neurons.In VGAT-ChR2-EYFP mice,the expression of exogenous gene ChR2-EYFP was controlled by the VGAT promoter,so ChR2-EYFP could specifically express in GABA neurons.Here I used VGAT-ChR2-EYFP mice to study the regulation of induced instantaneous slow wave sleep(SWS)on memory processes by activating PZ GABA neurons through blue light illumination.First of all,I photostimulated the PZ GABA neurons in VGAT-ChR2-EYFP mice through blue illumination during active period and induced 30 min SWS.Then,memory related behavioral experiments were carried out,including Novel Object Recognition(NOR),Y maze and fear memory test.Moreover,I studied the effect of induced 30min SWS on encoding,consolidation and retrieval of memory.In the object-in-place task that is one type of NOR,30 min induced SWS immediately and 15 min after the sample phase could significantly strengthen memory consolidation during test phase.But the enhancement effect disappeared if 30min induced SWS took place 30 min after learning.At the same time,15 min induced SWS immediately after learning could also enhance memory.Results above suggest that memory consolidation usually takes place immediately after learning.30 min induced SWS immediately after learning can significantly enhance recognition memory and the critical time window of the effect of SWS on memory consolidation is the first 30 min after learning.Next,we carried out Y-maze and fear conditioning test.In these two tasks,30 min induced SWS immediately after learning could also significantly enhance the spatial memory in Y-maze and contextual fear memory but had no significant effect on cued memory.And after learning in object-in-place task,30-min induced SWS in mice accompanied by sharp wave ripples recorded in the hippocampal CA1 field potential(100-250 Hz).Furthermore,compared with 15-min induced SWS,30-min induced SWS generated more ripple events in the CA1 region of hippocampus,and better memory performance in the object-in-place task,suggesting that optogenetically-induced SWS enhanced memory probably through sharp wave ripples observed in hippocampus.Meanwhile,30-min induced SWS before test phase in the object-in-place and Y-maze had no effect on memory performance,suggesting that 30-min induced SWS had no significant effect on memory retrieval.In addition,the 30-min induced SWS before the sample phase increased the memory performance in the object-in-place task but not the Y-maze spatial memory task.In summary,30-min induced SWS immediately after learning can significantly enhance hippocampus-dependent memory consolidation,and the precise time window is 30 min immediately following the learning,accompanying by high frequency sharp wave ripples recorded in the hippocampal CA1 local field potential that probably is underlying mechanism of enhancement.At the same time,30-min induced SWS had enhancement effect on encoding of recognition memory in object-in-place but no significant effect on the encoding of spatial memory in Y-maze and the retrieval of these two kinds of memory.