3. Role of ripples on memory consolidation
SWRs are bursts (50-100 ms) of cell activity in the hippocampal local field during a pause in active exploration or while asleep. Sharp wave ripples encompass two distinct components, namely sharp waves and ripples, which collectively constitute this neural phenomenon. Sharp waves refer to brief, high-amplitude waveforms that are characterized by a rapid and synchronized depolarization followed by a slower, hyperpolarizing phase. On the other hand, ripples are fast oscillations that occur within the context of sharp waves. Ripples are high-frequency oscillations in the range of 100-250 Hz and are superimposed on the sharp wave waveform. Sharp wave ripples, as a whole, refer to the combined occurrence of these two phenomena. The timescale at which SWRs are presented aligns with the optimal window to induce synaptic plasticity, and therefore, they have been accepted as a definite biomarker for the encoding of memory fingerprints on synaptic weights (Buzsáki, 2015; Cowen et al., 2020; Evangelista et al., 2020; Oliva et al., 2020; Roumis and Frank, 2015). Brain rhythms, such as slow waves, ripples, and spindles, happen at approximately the same speed in mammals, irrespective of brain size (Buzsáki et al., 2013). Several electroencephalography traces of mammals from the literature and their reported characteristics have been summarized and compared by Buzsáki et al. (2013).
Studies suggest that the CA3 region is the source of SPW in the hippocampus, as the spatial distribution of spontaneous SPW closely resembles that of Schaffer collateral evoked responses (Buzsáki et al., 1983). Also, evidence demonstrates that the blockage of CA3 output of the trisynaptic hippocampal circuit impairs the consolidation of contextual fear memory and the CA1 ripples and the ripple-associated reactivation of experience-dependent firing patterns of CA1 neurons, underlie the importance of the trisynaptic circuit and SWR in the consolidation of hippocampus-dependent memory (Nakashiba et al., 2009). Similarly, the SWR are physiological events associated with replay (multifactorial event) that underlie memory consolidation in the trisynaptic hippocampal circuit and the organization of this replay is influenced by the brain state (Buszáki, 1989, 2015), then during replay, SWR are also influenced by other factors in the trisynaptic circuit, such as genetic, microcircuits and behavioral states. De la Prida (2020) analyzes, under scrutiny based on the evidence, some of these factors in the CA1 hippocampal region, such as cell-type and input-specific connectivity as well as radial expression of receptors and intrinsic properties that influence the replay.
Additionally, the behavior of CA3 cells can be compared to that of pacemaker cells, as they exhibit early firing during population events and recruit follower cells to fire (Wittner and Miles, 2007). As described before, these pyramidal cells have extensive axon collaterals that project to both CA3 and CA1 regions, and the synapses they form account for most connections within the hippocampus (Amaral and Witter, 1989). Although recent research has called into question the extent of connectivity in CA3 (Guzman et al. 2016).
A group of interneurons cooperate to coordinate temporally and spatially the spike content of SWRs to replay the awake neuronal sequence segments in a compressed manner (Buzsáki, 2015). The connections between these interneurons and the pyramidal neurons are organized in a precise and intricate manner to allow for the generation and propagation of SWRs (Buzsáki, 2015). Parvalbumin -positive basket cells and oriens lacunosum-moleculare cells form local inhibitory circuits within the hippocampus, with their axons forming perisomatic and dendritic synapses on pyramidal neurons, respectively. These inhibitory connections help to shape the spatiotemporal patterns of SWRs and regulate the timing and coordination of the network activity during SWRs (Klausberger and Somogyi, 2008). It has been demonstrated that parvalbumin -positive basket cells fire before oriens lacunosum-moleculare during multiple brain rhythms including ripples and theta waves (Varga et al., 2012).
Axo-axonic cells have been shown to preferentially fire just after the peak of the theta cycles and discharge transiently at the beginning of SWRs (Klausberger et al., 2003). Other interneurons, such as ivy cells, appear to be only weakly modulated by SWRs (Buzsáki, 2015). However, the exact mechanisms underlying SWRs are still an active area of research, and further studies are needed to fully understand the complex interplay of interneurons in SWR generation and propagation.
After a sharp wave event, there is a brief period during which hyperpolarization occurs, ending the wave and creating a refractory period (Buzsáki, 2015). Specific groups of active cells that encode a particular memory tend to be preferentially replayed during SWRs (Wilson and McNaughton, 1994). During SWR replay, newly obtained and previously known knowledge is merged to affect judgements, plan actions, and maybe inspire original ideas (Buzsáki, 2015).
SWRs have been shown to be critically involved in the process of episodic memory consolidation (Jadhav et al., 2012). Spatial learning requires remembering and choosing paths to goals (Shin et al., 2019). Disruption of SWRs impairs spatial memory (Buzsáki, 2015), which consolidation depends on the reactivation of hippocampal place cells that were active during recent behavior (Oliva et al., 2020). Continuous track of hippocampal-prefrontal ensembles throughout learning of a spatial alternation task demonstrated that during pauses between behavioral trajectories, reverse and forward hippocampal replay supports an internal cognitive search of available past and future possibilities and exhibits opposing learning gradients for prediction of past and future behavioral paths, respectively (Shin et al., 2019).
Examination of the role of SWRs during the consolidation of social memory—the ability of an animal to recognize and remember a member of the same species—revealed that CA2 pyramidal neurons that are active during social exploration of previously unknown conspecifics are reactivated during SWRs. This suggests that SWRs originating from different regions may have different functional roles: CA3 SWRs seem to be important for spatial memory, whereas consolidation of social memory requires SWRs arising in CA2 and object remapping dorsal CA1 and CA3 (Oliva et al., 2020).
Various changes in SWRs have been reported in different pathologies such as epilepsy (Mooij et al., 2022), models of Alzheimer’s disease (Jones et al., 2019; Stoiljkovic et al., 2019; Prince et al., 2021; Caccavano et al., 2020), and aging (Cowen et al., 2020; Witton et al., 2014). However, little evidence has been reported on the effect of alcohol on SWRs and memory consolidation. According to a study by Krawczyk et al. (2016), increased duration and amplitude were observed in SPW waveforms when evaluating the effect of prenatal ethanol exposure on recordings from CA3 hippocampal pyramidal cells in vitro . A previous experiment was done by Mikaye et al. to analyze the effect of acute ethanol administration on the spike patterns of hippocampal cell populations. Their results suggested that ethanol does not significantly alter the frequency of hippocampal SWRs (Miyake et al., 2020). While these studies provide valuable insights into the effects of ethanol exposure on SPW waveforms, further investigations are warranted to fully elucidate the complex relationship between chronic alcohol use and SWRs. Advancing our knowledge in this area can have important implications for addressing alcohol-related cognitive impairments and developing targeted interventions.
Understanding the role of hippocampal ripples in memory consolidation is crucial for elucidating the mechanisms underlying alcohol-induced memory impairments. However, as have been revised, analyzing ripple activity can be challenging due to the complex and dynamic nature of these events, as well as the variability in the methods used to detect and quantify them.
To address these challenges, researchers have developed a range of analytical models and techniques aimed at improving the accuracy, reliability, and reproducibility of ripple analyses. The use of these analysis models is essential for understanding the functional significance of hippocampal ripples and their relationship with memory consolidation (Girardeau, 2021, Creery, 2022). As can be seen in the next section of this paper, by providing more accurate and reliable measures of ripple activity, these techniques can help to elucidate the neural mechanisms underlying memory processes and the effects of various factors, such as alcohol consumption, on these processes.
Moreover, these techniques can facilitate comparisons between different experimental conditions and between different studies, thereby enhancing the generalizability and reproducibility of findings across different research contexts.