Age Is Associated with Reduced Sharp-Wave Ripple Frequency and Altered Patterns of Neuronal Variability

Abstract

Spatial and episodic memory performance declines with age, and the neural basis for this decline is not well understood. Sharp-wave ripples are brief (ϳ70 ms) high-frequency oscillatory events generated in the hippocampus and are associated with the consolidation of spatial memories. Given the connection between ripple oscillations and memory consolidation, we investigated whether the structure of ripple oscillations and ripple-triggered patterns of single-unit activity are altered in aged rats. Local field and single-unit activity surrounding sharp-wave ripple events were examined in the CA1 region of the hippocampus of old (n ϭ 5) and young (n ϭ 6) F344 rats during periods of rest preceding and following performance on a place-dependent eyeblink-conditioning task. Neural responses in aged rats differed from responses in young rats in several ways. First, compared with young rats, the rate of ripple occurrence (ripple density) is reduced in aged rats during postbehavior rest. Second, mean ripple frequency during prebehavior and postbehavior rest is lower in aged animals (aged: 132 Hz; young: 146 Hz). Third, single neurons in aged animals responded more consistently from ripple to ripple. Fourth, variability in interspike intervals was greater in aged rats. Finally, neurons were tuned to a narrower range of phases of the ripple oscillation relative to young animals. Together, these results suggest that the CA1 network in aged animals has a reduced "vocabulary" of available representational states.

Age‐associated changes in waking hippocampal sharp‐wave ripples

“…Given the involvement of ripples in variable reinforcement learning (Ambrose et al, 2016), we predicted that ripple rates would increase after animals received an eye shock. We also predicted that aging would reduce the rate of ripple events and the oscillatory frequency of ripples, as has been previously reported for rest-associated ripples (Wiegand et al, 2016). …”

“…Furthermore, Gerrard et al (2001) demonstrated that aged and young rats express intact memory trace reactivation during rest-associated ripples, but that the temporal organization of reactivated events is reduced in aged animals (Gerrard et al, 2008). Similarly, Wiegand et al (2016) observed reduced reactivation in aged rats, and this reduction was largely due to a reduced rate of occurrence of ripples in aged animals. Wiegand et al (2016) also demonstrated that the oscillatory frequency of ripples was reduced by approximately 15 Hz in aged animals.…”

“…Similarly, Wiegand et al (2016) observed reduced reactivation in aged rats, and this reduction was largely due to a reduced rate of occurrence of ripples in aged animals. Wiegand et al (2016) also demonstrated that the oscillatory frequency of ripples was reduced by approximately 15 Hz in aged animals. It is important to note that in this study, age-associated changes in the rate of occurrence, oscillatory frequency of ripples, and the strength of reactivation did not correlate with measures of learning.…”

“…Signals were then bandpass filtered (115 to 250 Hz, 8 th order IIR Butterworth filter). We chose 115 Hz as a lower band given our previous finding that ripple oscillation frequencies are ~15 Hz lower in aged relative to young rats with a lower bound approaching 120 Hz (Wiegand et al, 2016). A candidate high-frequency event was identified when the envelope of the absolute value of the filtered signal exceeded 3 sds above the mean, lasted for at least 30 ms, and had a peak frequency in the PSD from 115 to 240 Hz of ≥ 120 Hz.…”

“…Although ripples occurring during sleep are believed to facilitate memory consolidation, waking ripples may also be involved in planning and memory retrieval. Recent work from our group determined that normal aging results in a significant reduction in the peak oscillatory frequency and rate-of-occurrence of ripples during sleep (Wiegand et al, 2016) that may contribute to age-associated memory decline. It is unknown, however, how aging alters waking ripples.…”