Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Apr 15;23(5):238-48.
doi: 10.1101/lm.040923.115. Print 2016 May.

Ripple-triggered stimulation of the locus coeruleus during post-learning sleep disrupts ripple/spindle coupling and impairs memory consolidation

Yulia Novitskaya  1 , Susan J Sara  2 , Nikos K Logothetis  3 , Oxana Eschenko  4
Affiliations

Ripple-triggered stimulation of the locus coeruleus during post-learning sleep disrupts ripple/spindle coupling and impairs memory consolidation

Yulia Novitskaya et al. Learn Mem. .

Abstract

Experience-induced replay of neuronal ensembles occurs during hippocampal high-frequency oscillations, or ripples. Post-learning increase in ripple rate is predictive of memory recall, while ripple disruption impairs learning. Ripples may thus present a fundamental component of a neurophysiological mechanism of memory consolidation. In addition to system-level local and cross-regional interactions, a consolidation mechanism involves stabilization of memory representations at the synaptic level. Synaptic plasticity within experience-activated neuronal networks is facilitated by noradrenaline release from the axon terminals of the locus coeruleus (LC). Here, to better understand interactions between the system and synaptic mechanisms underlying "off-line" consolidation, we examined the effects of ripple-associated LC activation on hippocampal and cortical activity and on spatial memory. Rats were trained on a radial maze; after each daily learning session neural activity was monitored for 1 h via implanted electrode arrays. Immediately following "on-line" detection of ripple, a brief train of electrical pulses (0.05 mA) was applied to LC. Low-frequency (20 Hz) stimulation had no effect on spatial learning, while higher-frequency (100 Hz) trains transiently blocked generation of ripple-associated cortical spindles and caused a reference memory deficit. Suppression of synchronous ripple/spindle events appears to interfere with hippocampal-cortical communication, thereby reducing the efficiency of "off-line" memory consolidation.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Ripple-triggered phasic LC stimulation. Extract of the raw (top trace) and band-pass (120–240 Hz) filtered CA1-LFP signal. The ripple peaks, on/off sets, and pulse trains (10 pulses, 0.05 mA at 100 Hz) delivered to the LC are shown on three bottom traces. Asterisk indicates the ripple that is illustrated at higher temporal resolution on the right panel. Note LC stimulation was applied immediately after ripple onset and did not affect generation of the ongoing ripple.
Figure 2.
Figure 2.
Effects of phasic LC stimulation on cortical EEG. (A) EEG power spectrum averaged over all SWS episodes during 1-h recording session. Dashed line: control recording without LC stimulation, solid lines with open and filled circles: LFS- and HFS-groups, respectively. (B) The group averages of prestimulus normalized band-limited power of cortical EEG around the stimulation onset are shown for RT-LFS (left panel) and RT-HFS (right panel). The BLP for each frequency range was normalized to 2 sec prestimulus interval and converted to z-scores. Gray bar indicates duration of the pulse train, a color bar represents z-scores. Note a transient frequency-specific power modulation elicited by the HFS, and the absence of the EEG spectral change in the case of the LFS.
Figure 3.
Figure 3.
Effects of LC stimulation on a spatial task acquisition. Average performance accuracy (A,C) and trial time (B,D) are plotted across eight daily training sessions for different experimental groups. (Open circles) nonstimulated control, (open squares) RT-LFS, (filled squares) RT-HFS, and (filled circles) random-HFS. Note strong learning deficit in the RT-HFS group.
Figure 4.
Figure 4.
Post-learning ripple-triggered LC activation causes a reference memory deficit. Bars represent the group means on the last day of training for the number of rewards retrieved (A), performance accuracy (B), and trial time (C). Note significant learning deficit was present exclusively in the RT-HFS group. (*) P < 0.05, (**) P < 0.01, and (***) P < 0.001 compared with nonstimulated control (Dunnett's test). (NS) nonstimulated control, (RT-LFS) ripple-triggered low-frequency LC stimulation, (RT-HFS) ripple-triggered high-frequency LC stimulation, (RD-HFS) random high-frequency LC stimulation.
Figure 5.
Figure 5.
Effects of phasic LC activation on ripple and spindles occurrence. Probability of ripples (A) and spindles (B) around onset of LC stimulation (t = 0). (Open squares) RT-LFS, (filled squares) RT-HFS, and (filled circles) random-HFS. Dashed lines indicate lower and upper 95% confidence levels of prestimulation interval. Note a transient suppression of spindles and ripples following HFS. Ripple probability is expectedly high in cases of the ripple-triggered stimulation. Log scale for ripple probability on A is used for illustration purpose. (C) Post-stimulation ripple probability for RT-LFS (open bars) and RT-HFS (black bars). Solid line shows the interripple probability during nonstimulated condition; dashed lines indicate lower and upper 95% confidence levels. (D) Interspindle interval during nonstimulated (dashed line) and HFS (solid line with filled circles) conditions. Inset shows interspindle interval for the LFS group. Note sleep spindle suppression during HFS.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aston-Jones G, Bloom FE. 1981. Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli. J Neurosci 1: 887–900. - PMC - PubMed
    1. Bailey CH, Giustetto M, Huang Y-Y, Hawkins RD, Kandel ER. 2000. Is heterosynaptic modulation essential for stabilizing Hebbian plasticity and memory?. Nat Rev Neurosci 1: 11–20. - PubMed
    1. Battaglia FP, Sutherland GR, McNaughton BL. 2004. Hippocampal sharp wave bursts coincide with neocortical “up-state” transitions. Learn Mem 11: 697–704. - PMC - PubMed
    1. Battaglia FP, Benchenane K, Sirota A, Pennartz CM, Wiener SI. 2011. The hippocampus: hub of brain network communication for memory. Trends Cogn Sci 15: 310–318. - PubMed
    1. Behrens CJ, van den Boom LP, de Hoz L, Friedman A, Heinemann U. 2005. Induction of sharp wave-ripple complexes in vitro and reorganization of hippocampal networks. Nat Neurosci 8: 1560–1567. - PubMed

Publication types

MeSH terms

LinkOut - more resources