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.