Fear memory consolidation in sleep requires protein kinase A

Abstract

It is well established that protein kinase A (PKA) is involved in hippocampal dependent memory consolidation. Sleep is also known to play an important role in this process. However, whether sleep-dependent memory consolidation involves PKA activation has not been clearly determined. Using behavioral observation, animals were categorized into sleep and awake groups. We show that intrahippocampal injections of the PKA inhibitor Rp-cAMPs in post-contextual fear conditioning sleep produced a suppression of long-term fear memory, while injections of Rp-cAMPs during an awake state, at a similar time point, had no effect. In contrast, injections of the PKA activator Sp-cAMPs in awake state, rescued sleep deprivation-induced memory impairments. These results suggest that following learning, PKA activation specifically in sleep is required for the consolidation of long-term memory.

Hippocampal cellular functional organization for fear memory: Effects of sleep

“…Fear memory was measured 24 h later in the same context. Similar to our previous results (Cho et al, 2018), Awake animals showed less freezing, compared with Sleep animals and Sleep animals showed a retention of conditioned fear, in the 24 h Test session. Results are presented as Mean ± SEM values.…”

“…A second objective of the study was to determine whether sleep may play a role in the formation of clusters or perhaps their maintenance. Numerous studies have now provided evidence that sleep plays a significant role in memory consolidation—the amount of sleep (mainly rapid eye movement sleep, REM) is augmented following a learning experience (Destrade et al, 1978; Fishbein et al, 1974; Hennevin et al, 1995; Lucero, 1970; Portell‐Cortés et al, 1989; Smith et al, 1977; Smith & Rose, 1997; Smith & Wong, 1991), while sleep deprivation following learning produces an impairment of long‐term memory (Alvarenga et al, 2008; Binder et al, 2012; Chen et al, 2006; Cho et al, 2018; Fishbein, 1971; Graves et al, 2003; Hagewoud et al, 2010; Ishikawa et al, 2014; Palchykova et al, 2006; Pearlman, 1973; Prince et al, 2014; Ravassard et al, 2016; Silva et al, 2004; Smith et al, 1998; Smith & Butler, 1982; Smith & Rose, 1996). Sleep or the lack of, has also been shown to suppress synaptic plasticity (i.e., long‐term potentiation), which is a model of learning and memory (Campbell et al, 2002; Chen et al, 2006; Kopp et al, 2006; Ravassard et al, 2009; Romcy‐Pereira & Pavlides, 2004; Vecsey et al, 2009) (for review, see Rasch & Born, 2013).…”

Sleep loss drives acetylcholine- and somatostatin interneuron–mediated gating of hippocampal activity to inhibit memory consolidation

“…SD interferes with biochemical pathways which drive increased protein synthesis following learning ( 9 , 11 ). This suggests a link between state-dependent changes in network activity and biosynthetic events occurring in the first few hours following learning ( 12 – 15 ), which are necessary for appropriate CFM consolidation.…”

Post-synaptic competition between calcineurin and PKA regulates mammalian sleep-wake cycles

“…The enzymes PKA, PP1, and CaN, which were highlighted in our recent study, are also known for their roles in synaptic plasticity 61 . PKA is recognized as a factor responsible for memory consolidation including the consolidation during sleep 62 . Neurabin-2 has been implicated in neural plasticity and memory consolidation as well 63–65 , while the enzymatic activity of PP1 is also involved in memory extinction 66 .…”