Hippocampal CA3 Output is Crucial for Ripple-Associated Reactivation and Consolidation of Memory

By T. Nakashiba, D. Buhl, T. McHugh, S. Tonegawa. 2009

291 citations recorded by the source corpus.

SUMMARY A widely held memory consolidation theory posits that memory of events and space is initially stored in the hippocampus (HPC) in a time-limited manner and is consolidated in the neocortex for permanent storage. Although post-training HPC lesions result in temporally graded amnesia, the precise HPC circuits and mechanisms involved in remote memory storage remain poorly understood. To investigate the role of the trisynaptic pathway in the consolidation process we employed the CA3-TeTX transgenic mouse, in which CA3 output can be specifically and inducibly controlled. We found that post-training blockade of CA3 output for up to four weeks impairs the consolidation of contextual fear memory. Moreover, in vivo hippocampal recordings revealed a reduced intrinsic frequency of CA1 ripples and a significant decrease in the experience-dependent, ripple-associated coordinated reactivation of CA1 cell pairs. Collectively, these results suggest that the post-training integrity of the trisynaptic pathway and the ripple-associated reactivation of hippocampal memory engram is crucial for memory consolidation.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Neurology

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Citations in the corpus

Hippocampal Replay is Not a Simple Function of Experience (2010, background): “, 1995) (Nakashiba et al., 2009) and have directly disrupted SWRs after learning, during sleep (Girardeau et al.”
Transcranial pulsed ultrasound stimulates intact brain circuits. (2010, background): “, 1995) and have recently been shown to underlie memory storage in behaving rodents (Girardeau et al., 2009; Nakashiba et al., 2009).”
The content of hippocampal “replay” (2018, background): “…slow-wave sleep, quiet rest, grooming, and eating/drinking (Buzs aki, 1986, 2015), and disruption in their expression results in significant memory impairments (Ego-Stengel & Wilson, 2010; Girardeau et al., 2009; Jadhav et al., 2012; Nakashiba et al., 2009; Nokia et al., 2012; Wang et al., 2015a).”
Contextual Fear Memories Formed in the Absence of the Dorsal Hippocampus Decay Across Time (2012, background): “…memories to be stored permanently is supported by studies showing that memories formed in the remote past can be disrupted by blocking CA3 output, therein disturbing the integrity of the tri-synaptic pathway and the ripple-associated reactivation of hippocampal memory (Nakashiba et al., 2009).”
What Learning Systems do Intelligent Agents Need? Complementary Learning Systems Theory Updated. (2016, unknown): “A causal role for replay is supported by studies showing that the disruption of ripples in the hippocampus produces a signi ﬁ cant impairment in systems-level consolidation in rats [67 – 69].”
The reorganization and reactivation of hippocampal maps predict spatial memory performance (2010, unknown): “During off-line rest periods, sSWRs have been suggested to promote memory consolidation because waking activity patterns of place cells are reactivated during these network events 26 - 28 , 35 , 38 .”