Disrupting neural activity related to awake-state sharp wave-ripple complexes prevents hippocampal learning - PubMed (original) (raw)
Disrupting neural activity related to awake-state sharp wave-ripple complexes prevents hippocampal learning
Miriam S Nokia et al. Front Behav Neurosci. 2012.
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.
Keywords: classical conditioning; hippocampus; learning; ripple; theta.
Figures
Figure 1
Conditioning procedure. Training over days for the control group (top) and for the SPW-R-contingent (R) and yoked control (Y) (bottom) groups is depicted in (A). All animals initially received one unpaired session followed by 8 daily sessions of trace eyeblink conditioning. The conditioning sessions consisted of 60 trials with an average inter-trial interval (ITI) of 30 s. During a single trial, the tone-CS onset preceded the airpuff-US onset by 700 ms, thus creating a 500-ms stimulus-free trace period. Animals from the Y and R groups were grouped into pairs and trained together (see B). During the ITI, a flash of light was presented every time a ripple was detected in the animal assigned to the R group. After this, animals in the R and Y groups were trained for another 5 daily sessions now omitting the light.
Figure 2
Placement of recording electrodes in the dorsal hippocampus. Electrodes used in the yoked control (Y) and SPW-R-contingent (R) groups for detecting ripples (left, R: n = 9, Y: n = 10) and analyzing theta (right, R: n = 8, Y: n = 8). Only animals that learned are included.
Figure 3
Hippocampal theta-band responses (A and B) and behavioral responses (C) to the light stimulus were similar in the yoked control (Y) and SPW-R-contingent (R) groups. In addition, no changes across training were evident. In subplot (A), gray bars indicate the light.
Figure 4
Flashing a light during inter-trial intervals retarded learning most when done contingent upon hippocampal SPW-Rs. During the first 8 training sessions, animals in the yoked control (Y) and SPW-R-contingent (R) groups received a light stimulus during the inter-trial interval every time a SPW-R was detected in an animal belonging to the R group (Disruption), whereas the animals in the normal control group (N) did not receive any light stimuli. After that, animals in the yoked control and SPW-R-contingent groups were trained for another 5 days, this time omitting the light (No disruption). Vertical lines depict s.e.m. Asterisks refer to repeated-measures ANOVA group effects: *p < 0.05, ***p < 0.001.
Figure 5
SPW-R-contingent triggering of light presentations. Online SPW-R-contingent triggering of light presentations in a representative animal is depicted in (A). In (B) and (C), traces represent averages of SPW-Rs recorded during one session in a representative animal (same as in panel A). SPW-Rs were either followed by a light (Light) or not (Undisrupted). In (C), a subset of panel (B) is presented focusing on the SPW-R. Light did not affect the SPW-R itself, but only the neural activity following it (B and C). SPW-Rs occurred at a rate of approximately 7–11 per minute (D). More SPW-Rs were observed in both groups as conditioning proceeded (rm ANOVA, main effect of session, p < 0.001). Most SPW-Rs occurred 8 or more seconds after the training trial had ceased (E). SPW-Rs tended to occur in close temporal proximity to each other (F). No statistically significant differences between the R and the Y group were observed in the timing of SPW-Rs in relation to training trials or each other. Vertical lines in (D–F) depict s.e.m.
Figure 6
Flashing a light during inter-trial intervals contingent upon awake-state SPW-Rs disrupted the phase-locking of hippocampal theta-band (4–12 Hz) responses to the conditioning stimuli. Phase-locking at the beginning of training, at the end of the first phase of training and at the end of all training is depicted in (A). Traces represent grand average of each group. In (B), phase-locking to both stimuli is presented as a function of training session. Note that the values presented in (B) are derived from a 500-ms period following the onset of the stimulus by 200 ms, thus ensuring that the event-related potential was excluded from analysis. Gray bars indicate the timing of the conditioning stimuli. Horizontal dotted line indicates the statistical significance (p = 0.01) of phase-locking. Vertical lines depict s.e.m. *p < 0.05.
Figure A1
A custom-made device was used for ripple-contingent triggering of the light stimulus. The signal was band-pass filtered (Texas Instruments FilterPro: center frequency 150 Hz, four poles, Q = 1) and the polarity of the filtered signal reversed. When this processed signal exceeded the threshold value defined by the user the device produced a 200-ms TTL pulse and a simultaneous flash of light from the LEDs. The computer and software (E-Prime) used to control the presentation of the conditioning stimuli was also used to block light presentation immediately before and during the training trial via delivering a TTL pulse to this custom-made device.
Figure A2
Number and distribution of ripples in a group of rabbits trained without the light stimulus (n = 12, see Nokia et al., 2010). Data from our previous study (Nokia et al., 2010) yoked control group, first 8 sessions of conditioning was reanalyzed. As in the SPW-R-contingent and yoked control groups in our current study, the frequency of ripples during the inter-trial interval increased across sessions (rm ANOVA, main effect of session p < 0.05) and was around 7–11 per minute (A). Also similar to the yoked control and SPW-R-contingent groups in the current study, most SPW-Rs occurred 8 or more seconds after the training trial had ceased (B) and SPW-Rs tended to occur in close temporal proximity to each other (C). Note that formatting of this figure (including y-axis scale) is identical to Figure 5 panels (D–F).
References
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- Buzsáki G. (2002). Theta oscillations in the hippocampus. Neuron 33, 325–340 -PubMed
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