Coherent amygdalocortical theta promotes fear memory consolidation during paradoxical sleep

Abstract

Brain activity in sleep plays a crucial role in memory consolidation, an offline process that determines the long-term strength of memory traces. Consolidation efficacy differs across individuals, but the brain activity dynamics underlying these differences remain unknown. Here, we studied how interindividual variability in fear memory consolidation relates to neural activity in brain structures that participate in Pavlovian fear learning. From the end of training to testing 24 h later, some rats showed increased and others decreased conditioned fear responses. We found that overnight bidirectional changes in fear memory were selectively correlated with modifications in theta coherence between the amygdala, medial prefrontal cortex, and hippocampus during paradoxical sleep. Thus, our results suggest that theta coordination in the limbic system may influence interindividual differences in memory consolidation of aversive experiences.amygdala | fear conditioning | prefrontal cortex | hippocampus | Granger causality R ecently formed memories undergo a period of consolidation (1, 2), and neuronal activity taking place during sleep is thought to play a critical role in this process (3-7). Consolidation of emotional memories determines their long-term retention, and interindividual variations in memory performance have been related to various factors affecting consolidation, including neuromodulatory transmission (8), levels of circulating stress hormones (9), or genetic factors (10). Several strongly interconnected brain structures are involved in the formation and maintenance of emotional memories, including the hippocampus (Hi), medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) (11-13). The latter structure in particular was shown to mediate the facilitating effects of emotions on memory consolidation (14). Indeed, we form more vivid and enduring memories for emotionally arousing experiences (15). Via the release of peripheral stress hormones (16), emotional arousal causes long-lasting increases in the firing rate of BLA neurons (17), and pharmacologic manipulations that prevent this increased activity interfere with memory for events that took place shortly before, in many learning tasks (18). Importantly, in most learning paradigms, the same interventions performed shortly before testing long-term memory recall have no effect, indicating that the BLA can facilitate the consolidation of memories in other brain structures (14,18).Potentially related to the facilitation of emotional memories by BLA activity, various lines of evidence implicate posttraining paradoxical sleep (PS) in memory consolidation (6,19). These include PS reactivation of brain areas implicated in prior learning (20) and spontaneous replay of waking activity patterns during PS (21). In fact, it was suggested that the distinct pattern of neuronal activity occurring during PS favors memory consolidation (4,22) and that emotional memories are particularly susceptible to this effect (5, 23). Indeed, after fear conditioning, the respons...

Sleep and Emotional Functions

“…Other reward-related regions, like the ventromedial PFC (Haber and Knutson 2010) and the ACC, which assign a positive or negative value to future outcomes (Bush et al 2002;Takenouchi et al 1999), are activated during REM sleep, in both animals and humans (Lena et al 2005;Maquet et al 1996Maquet et al , 2000. In addition, neuronal activity in the hippocampus displays a theta rhythm (i.e., an oscillatory pattern in EEG with a frequency range of 5-12 Hz in behaving rats and 4-7 Hz in humans) during REM sleep in both animals (Popa et al 2010;Winson 1972) and humans (Cantero et al 2003) studies. This latter finding is remarkable considering that increased theta oscillations have been reported during novelty-seeking, exploratory and instinctual behaviors, which are also seen in REM sleep behavior disorder and other parasomnias .…”

Observation of Distressed Conspecific as a Model of Emotional Trauma Generates Silent Synapses in the Prefrontal-Amygdala Pathway and Enhances Fear Learning, but Ketamine Abolishes those Effects

“…Elevated c-Fos expression in dmPFC and BLA after OF indicated that modifications may involve the dmPFC-BLA Emotional trauma generates silent synapses W Ito et al pathway. Given the dmPFC-BLA interactions are required for PA learning (Malin et al, 2007;Malin and McGaugh, 2006) and correlate with fear memory (Lesting et al, 2011;Popa et al, 2010), the formation of new silent synapses is a potential mechanism to enhance PA learning via strengthening dmPFC-BLA connectivity.…”

“…Emotionally salient stimuli generally recruit the dorsomedial prefrontal cortex (dmPFC) and the basolateral amygdala (BLA), which have strong reciprocal projections (Hubner et al, 2014;McDonald, 1998) and are involved in fear learning (Gilmartin et al, 2014;Marek et al, 2013;Senn et al, 2014), including contextual learning during observational fear (Amano et al, 2010;Jeon et al, 2010). Fear learning increases oscillatory synchronization between the two structures (Lesting et al, 2011;Likhtik et al, 2014;Stujenske et al, 2014), the amplitude of which correlates with the strength of fear memory (Popa et al, 2010). On the other hand, synaptic inputs from the medial prefrontal cortex to BLA excitatory neurons become attenuated after fear extinction (Cho et al, 2013).…”

Integrated Brain Circuits: Neuron-Astrocyte Interaction in Sleep-Related Rhythmogenesis

“…Although recent experiments have shown a role for coherence between the amygdala and prefrontal cortex during rapid eye movement (REM) sleep in fear memory consolidation[25], the role of slow wave sleep (SWS) in memory consolidation has been more intensely studied (for review, see [6]). Network activity during SWS is thought to mediate many of the functions attributed to sleep in memory consolidation[10,26,27,28].…”