Disrupting neural activity related to awake-state sharp wave-ripple complexes prevents hippocampal learning

Abstract

Oscillations in hippocampal local-field potentials (LFPs) reflect the crucial involvement of the hippocampus in memory trace formation: theta (4–8 Hz) oscillations and ripples (~200 Hz) occurring during sharp waves are thought to mediate encoding and consolidation, respectively. During sharp wave-ripple complexes (SPW-Rs), hippocampal cell firing closely follows the pattern that took place during the initial experience, most likely reflecting replay of that event. Disrupting hippocampal ripples using electrical stimulation either during training in awake animals or during sleep after training retards spatial learning. Here, adult rabbits were trained in trace eyeblink conditioning, a hippocampus-dependent associative learning task. A bright light was presented to the animals during the inter-trial interval (ITI), when awake, either during SPW-Rs or irrespective of their neural state. Learning was particularly poor when the light was presented following SPW-Rs. While the light did not disrupt the ripple itself, it elicited a theta-band oscillation, a state that does not usually coincide with SPW-Rs. Thus, it seems that consolidation depends on neuronal activity within and beyond the hippocampus taking place immediately after, but by no means limited to, hippocampal SPW-Rs.

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

“…The competing networks hypothesis is further supported by the results of a recent study where ongoing neural activity during the intertrial interval was interrupted by bright flashes of light at times of ripple occurrence in the rabbit (Nokia et al 2012). Salient sensory stimulation in any modality elicits a burst of LC-NE neurons (Foote et al 1980;Herve-Minvielle and Sara 1995).…”

“…Salient sensory stimulation in any modality elicits a burst of LC-NE neurons (Foote et al 1980;Herve-Minvielle and Sara 1995). In this case, the visual stimulus presented at ripple onset transiently shifted hippocampal activity to the theta-oscillation state and caused impaired acquisition of a trace eye blink conditioning, a hippocampus-dependent associative learning task (Nokia et al 2012). Clearly, introducing any interference to the post-learning information processing either by disruption of activity within the supporting network or by coactivation of competing networks would lead to less efficient consolidation.…”

The impact of sleep loss on hippocampal function

“…In 2012, Nokia and colleagues demonstrated the necessity of SPW-R hippocampal events that are characteristic of SWS by disrupting SPW-R with electrical stimulation in rabbits. This manipulation impaired trace eyeblink conditioning, a hippocampus-dependent learning task (Nokia et al 2012). Other studies in humans have shown that reactivation during SWS can enhance not only spatial memory but also procedural memories, suggesting that reintroduction of cues during sleep may reactivate other brain regions as well (Antony et al 2012;Oudiette et al 2013).…”

“…The presentation of the auditory cue during SWS increased activation of the medial temporal lobe and altered parahippocampal-medial prefrontal connectivity, which has traditionally been associated with declarative memory (Van Dongen et al 2012). Not only has inducing neuronal replay during SWS been shown to enhance memory consolidation, but also SPW-R disruption impairs hippocampus-dependent memory (Girardeau et al 2009;Nokia et al 2012). In 2012, Nokia and colleagues demonstrated the necessity of SPW-R hippocampal events that are characteristic of SWS by disrupting SPW-R with electrical stimulation in rabbits.…”

Phase matters: responding to and learning about peripheral stimuli depends on hippocampal θ phase at stimulus onset

“…u is thought to reflect a state in which information about the surroundings is actively acquired (Buzsáki 1989). Animals exhibiting dominant hippocampal u during spontaneous recordings prior to training tend to learn better (Berry and Thompson 1978;Nokia et al 2009Nokia et al , 2012b, and high-amplitude, well phase-locked u-band hippocampal responses to the conditioned stimulus early in eyeblink conditioning predict good learning (Nokia et al 2009(Nokia et al , 2010(Nokia et al , 2012aNokia and Wikgren 2014). Training contingent on transient episodes of hippocampal u or its explicit absence has produced significant but somewhat inconsistent effects on learning (Griffin et al 2004;Nokia and Wikgren 2014).…”