Gamma oscillations and episodic memory

Gamma oscillations may coordinate pre- and postsynaptic neuronal firing to enhance plasticity within the hippocampus.Cross-regional gamma synchronisation may communicate sensory information to the hippocampus during memory formation, and hippocampal representations to the cortex during retrieval.Gamma oscillations nested within ongoing theta oscillations may encode and recall sequences of stimuli.Multiple, distinct oscillations may exist within the canonical gamma band (30–80 Hz), each with complementary roles in episodic memory. Enhanced gamma oscillatory activity (30–80 Hz) accompanies the successful formation and retrieval of episodic memories. While this co-occurrence is well documented, the mechanistic contributions of gamma oscillatory activity to episodic memory remain unclear. Here, we review how gamma oscillatory activity may facilitate spike timing-dependent plasticity, neural communication, and sequence encoding/retrieval, thereby ensuring the successful formation and/or retrieval of an episodic memory. Based on the evidence reviewed, we propose that multiple, distinct forms of gamma oscillation can be found within the canonical gamma band, each of which has a complementary role in the neural processes listed above. Further exploration of these theories using causal manipulations may be key to elucidating the relevance of gamma oscillatory activity to episodic memory. Enhanced gamma oscillatory activity (30–80 Hz) accompanies the successful formation and retrieval of episodic memories. While this co-occurrence is well documented, the mechanistic contributions of gamma oscillatory activity to episodic memory remain unclear. Here, we review how gamma oscillatory activity may facilitate spike timing-dependent plasticity, neural communication, and sequence encoding/retrieval, thereby ensuring the successful formation and/or retrieval of an episodic memory. Based on the evidence reviewed, we propose that multiple, distinct forms of gamma oscillation can be found within the canonical gamma band, each of which has a complementary role in the neural processes listed above. Further exploration of these theories using causal manipulations may be key to elucidating the relevance of gamma oscillatory activity to episodic memory. When we talk of episodic memories (see Glossary), we mean long-term memories relating to personally experienced events anchored to a specific moment in time and space [1.Tulving E. Episodic and semantic memory.in: Tulving E. Donaldson W. Organization of Memory. Academic Press, 1972: 381-403Google Scholar]. Although these memories are, by definition, rich in detail and can last for decades, patterns of neural activity lasting mere seconds will dictate whether these memories are formed or recalled [2.Staresina B.P. Wimber M. A neural chronometry of memory recall.Trends Cogn. Sci. 2019; 23: 1071-1085Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar,3.Hanslmayr S. et al.Oscillations and episodic memory – addressing the synchronization/desynchronization conundrum.Trends Neurosci. 2016; 39: 16-25Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar]. Many studies suggest that gamma oscillations (~30–80 Hz, although definitions can vary slightly among researchers) have a key role in both the formation and retrieval of an episodic memory. Supporting evidence comes from a range of species (including rodents [4.Zheng C. et al.Spatial sequence coding differs during slow and fast gamma rhythms in the hippocampus.Neuron. 2016; 89: 398-408Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar, 5.Bieri K.W. et al.Slow and fast gamma rhythms coordinate different spatial coding modes in hippocampal place cells.Neuron. 2014; 82: 670-681Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar, 6.Shirvalkar P.R. et al.Bidirectional changes to hippocampal theta-gamma comodulation predict memory for recent spatial episodes.Proc. Natl. Acad. Sci. U. S. A. 2010; 107: 7054-7059Crossref PubMed Scopus (166) Google Scholar, 7.Headley D.B. Weinberger N.M. Gamma-band activation predicts both associative memory and cortical plasticity.J. Neurosci. 2011; 31: 12748-12758Crossref PubMed Scopus (51) Google Scholar], nonhuman primates [8.Csorba B.A. et al.Long-range cortical synchronization supports abrupt visual learning.Curr. Biol. 2022; 32: 2467-2479Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar,9.Jutras M.J. et al.Gamma-band synchronization in the macaque hippocampus and memory formation.J. Neurosci. 2009; 29: 12521-12531Crossref PubMed Scopus (143) Google Scholar], and humans [10.Griffiths B.J. et al.Directional coupling of slow and fast hippocampal gamma with neocortical alpha/beta oscillations in human episodic memory.Proc. Natl. Acad. Sci. U.S.A. 2019; 166: 21834-21842Crossref Scopus (61) Google Scholar, 11.Heusser A.C. et al.Episodic sequence memory is supported by a theta-gamma phase code.Nat. Neurosci. 2016; 19: 1374-1380Crossref PubMed Scopus (147) Google Scholar, 12.Fell J. et al.Human memory formation is accompanied by rhinal–hippocampal coupling and decoupling.Nat. Neurosci. 2001; 4: 1259-1264Crossref PubMed Scopus (579) Google Scholar]), and a variety of empirical techniques (ranging from studies of cell cultures in vitro [13.Sjöström P.J. et al.Rate, timing, and cooperativity jointly determine cortical synaptic plasticity.Neuron. 2001; 32: 1149-1164Abstract Full Text Full Text PDF PubMed Scopus (833) Google Scholar,14.Markram H. et al.Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs.Science. 1997; 275: 213-215Crossref PubMed Scopus (2911) Google Scholar] to behavioural responses in humans [15.Wang D. et al.Altering stimulus timing via fast rhythmic sensory stimulation induces STDP-like recall performance in human episodic memory.bioRxiv. 2022; (Published online November 3, 2022. https://doi.org/10.1101/2022.11.02.514843)Google Scholar]). In our view, the extent of this evidence provides firm support for a link between gamma oscillations and episodic memory, and calls for a focus on understanding why this link exists. To address this question, we review three distinct neural mechanisms that may link gamma oscillations to fundamental aspects of episodic memory: (i) spike timing-dependent plasticity; (ii) neural communication; and (iii) sequence encoding/retrieval, with the aim of elucidating how gamma oscillatory activity supports episodic memory. Our ability to form an episodic memory hinges upon long-term potentiation (LTP), a process through which synaptic connections between two neurons are strengthened [16.Bliss T.V.P. Collingridge G.L. A synaptic model of memory: long-term potentiation in the hippocampus.Nature. 1993; 361: 31-39Crossref PubMed Scopus (9658) Google Scholar,17.Hebb D. The Organisation of Behavior. John Wiley & Sons, 1949Google Scholar]. Gamma oscillations have been proposed to play an important role in a type of LTP known as spike timing-dependent plasticity (STDP), which depends on a precise temporal delay between the firing of a presynaptic and a postsynaptic neuron. While there are numerous examples of gamma oscillatory activity enhancing STDP in vitro [13.Sjöström P.J. et al.Rate, timing, and cooperativity jointly determine cortical synaptic plasticity.Neuron. 2001; 32: 1149-1164Abstract Full Text Full Text PDF PubMed Scopus (833) Google Scholar,18.Whittington M.A. et al.Recurrent excitatory postsynaptic potentials induced by synchronized fast cortical oscillations.Proc. Natl. Acad. Sci. U.S.A. 1997; 94: 12198-12203Crossref PubMed Scopus (146) Google Scholar], in silico [19.Li K.T. et al.Gamma oscillations facilitate effective learning in excitatory-inhibitory balanced neural circuits.Neural Plast. 2021; 2021: 1-18Crossref Scopus (3) Google Scholar,20.Park K. et al.Optogenetic activation of parvalbumin and somatostatin interneurons selectively restores theta-nested gamma oscillations and oscillation-induced spike timing-dependent long-term potentiation impaired by amyloid β oligomers.BMC Biol. 2020; 18: 7Crossref PubMed Scopus (36) Google Scholar], and in vivo [21.Guerra A. et al.Boosting the LTP-like plasticity effect of intermittent theta-burst stimulation using gamma transcranial alternating current stimulation.Brain Stimulation. 2018; 11: 734-742Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar,22.Guerra A. et al.Enhancing gamma oscillations restores primary motor cortex plasticity in Parkinson's disease.J. Neurosci. 2020; 40: 4788-4796Crossref PubMed Scopus (0) Google Scholar], the mechanistic explanation of this link is open to debate. Here, we discuss: (i) how STDP occurs; (ii) how gamma oscillations may facilitate this process; and (iii) how the interaction between STDP and gamma oscillations might result in the formation of complex, episodic memories. STDP is thought to depend upon: (i) a presynaptic spike leading to the release of presynaptic glutamate, which promotes the opening of postsynaptic NMDA receptors; and (ii) the backpropagation of a postsynaptic spike leading to the unblocking of the Mg2+ block from the same postsynaptic NMDA receptors [16.Bliss T.V.P. Collingridge G.L. A synaptic model of memory: long-term potentiation in the hippocampus.Nature. 1993; 361: 31-39Crossref PubMed Scopus (9658) Google Scholar]. Some have suggested that the comparatively slow binding of glutamate to the NMDA receptor relative to the rapid removal of the Mg2+ block means that the presynaptic action potential must precede the postsynaptic action potential by ~10–20 ms for STDP to occur (e.g., [23.Nyhus E. Curran T. Functional role of gamma and theta oscillations in episodic memory.Neurosci. Biobehav. Rev. 2010; 34: 1023-1035Crossref PubMed Scopus (343) Google Scholar]). Indeed, in slices of rat hippocampus, presynaptic spikes that lead postsynaptic spikes by ~15 ms result in synaptic strengthening, whereas presynaptic spikes that follow postsynaptic spikes by ~6 ms lead to synaptic weakening (known as long-term depression; LTD) [24.Bi G. Poo M. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type.J. Neurosci. 1998; 18: 1-9Crossref PubMed Google Scholar]. STDP effects have been reported across a range of species, including rodents (in vitro [24.Bi G. Poo M. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type.J. Neurosci. 1998; 18: 1-9Crossref PubMed Google Scholar, 25.Wittenberg G.M. Wang S.S.-H. Malleability of spike-timing-dependent plasticity at the CA3-CA1 synapse.J. Neurosci. 2006; 26: 6610-6617Crossref PubMed Scopus (227) Google Scholar, 26.Froemke R.C. et al.Spike-timing-dependent synaptic plasticity depends on dendritic location.Nature. 2005; 434: 221-225Crossref PubMed Scopus (306) Google Scholar] and in vivo [27.Morera-Herreras T. et al.Environmental enrichment shapes striatal spike-timing-dependent plasticity in vivo.Sci. Rep. 2019; 9: 19451Crossref PubMed Scopus (6) Google Scholar]), nonhuman primates (in vitro [28.Huang S. et al.Associative Hebbian synaptic plasticity in primate visual cortex.J. Neurosci. 2014; 34: 7575-7579Crossref PubMed Scopus (36) Google Scholar] and in vivo [29.Seeman S.C. et al.Paired stimulation for spike-timing-dependent plasticity in primate sensorimotor cortex.J. Neurosci. 2017; 37: 1935-1949Crossref PubMed Scopus (29) Google Scholar]), and humans (in vitro [30.Testa-Silva G. Human synapses show a wide temporal window for spike-timing-dependent plasticity.Front. Synaptic Neurosci. 2010; 2: 12PubMed Google Scholar]). Although STDP depends upon correlated pre- and postsynaptic spiking, a solitary presynaptic spike is unlikely to induce postsynaptic spiking [16.Bliss T.V.P. Collingridge G.L. A synaptic model of memory: long-term potentiation in the hippocampus.Nature. 1993; 361: 31-39Crossref PubMed Scopus (9658) Google Scholar]. Instead, convergent input is required. Gamma oscillations may provide this convergent input in two ways. First, gamma oscillations can synchronise the firing of multiple presynaptic neurons so that they exert a stronger depolarising effect on the target postsynaptic neuron than if they were to fire in isolation [13.Sjöström P.J. et al.Rate, timing, and cooperativity jointly determine cortical synaptic plasticity.Neuron. 2001; 32: 1149-1164Abstract Full Text Full Text PDF PubMed Scopus (833) Google Scholar,14.Markram H. et al.Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs.Science. 1997; 275: 213-215Crossref PubMed Scopus (2911) Google Scholar]. Indeed, computational models show that the oscillation-driven synchrony of presynaptic activity increases the likelihood of a postsynaptic spike [31.Salinas E. Sejnowski T.J. Impact of correlated synaptic input on output firing rate and variability in simple neuronal models.J. Neurosci. 2000; 20: 6193-6209Crossref PubMed Google Scholar,32.Murthy V.N. Fetz E.E. Effects of input synchrony on the firing rate of a three-conductance cortical neuron model.Neural Comput. 1994; 6: 1111-1126Crossref Google Scholar] (see also [33.McNaughton B.L. et al.Synaptic enhancement in fascia dentata: cooperativity among coactive afferents.Brain Res. 1978; 157: 277-293Crossref PubMed Scopus (480) Google Scholar]). Moreover, in vitro studies show that synchronising multiple inputs to a postsynaptic neuron enhances the likelihood of LTP [13.Sjöström P.J. et al.Rate, timing, and cooperativity jointly determine cortical synaptic plasticity.Neuron. 2001; 32: 1149-1164Abstract Full Text Full Text PDF PubMed Scopus (833) Google Scholar]. While an oscillation of any frequency could, in theory, synchronise neuronal firing, gamma oscillations are perhaps ideal because they provide a comparatively short window of excitability that ensures all neurons fire in near-perfect unison [34.Jensen O. et al.Human gamma-frequency oscillations associated with attention and memory.Trends Neurosci. 2007; 30: 317-324Abstract Full Text Full Text PDF PubMed Scopus (872) Google Scholar], while having oscillatory cycles that are long enough to ensure that neurons return to their resting potential before the next excitatory part of the oscillation. In support of the former claim, LTP has been demonstrated to be most effective when pre- and postsynaptic firing is coupled to a 50-Hz rhythm (relative to slower rhythms) [13.Sjöström P.J. et al.Rate, timing, and cooperativity jointly determine cortical synaptic plasticity.Neuron. 2001; 32: 1149-1164Abstract Full Text Full Text PDF PubMed Scopus (833) Google Scholar], although it remains to be seen how LTP is affected when pre- and postsynaptic firing is coupled to a frequency greater than 50 Hz. In addition to facilitating synchronised neuronal firing, gamma oscillations may also aid the postsynaptic depolarisation necessary for STDP by inducing subthreshold oscillatory fluctuations in postsynaptic membrane potential. For example, in vitro work has shown that pairing presynaptic spikes to the peak of a 40-Hz oscillation led to greater LTP than when spikes were paired to the trough of the oscillation [35.Wespatat V. et al.Phase sensitivity of synaptic modifications in oscillating cells of rat visual cortex.J. Neurosci. 2004; 24: 9067-9075Crossref PubMed Scopus (137) Google Scholar], purportedly because the change in potential at the oscillatory peak adds an additional drive for depolarising the postsynaptic neuron. This may explain why, in humans and nonhuman primates, successful memory formation occurs when neuronal firing is coupled to particular phases of the ongoing gamma oscillation [9.Jutras M.J. et al.Gamma-band synchronization in the macaque hippocampus and memory formation.J. Neurosci. 2009; 29: 12521-12531Crossref PubMed Scopus (143) Google Scholar,36.Roux F. et al.Oscillations support short latency co-firing of neurons during human episodic memory formation.eLife. 2022; 11e78109Crossref Scopus (3) Google Scholar]. Considering all the above, it appears plausible that gamma oscillations can facilitate LTP by increasing the likelihood of postsynaptic spiking. Gamma oscillations may also provide a spike-timing delay between the pre- and postsynaptic neurons that is optimal for STDP (~10–20 ms) [37.Traub R.D. et al.Gamma-frequency oscillations: a neuronal population phenomenon, regulated by synaptic and intrinsic cellular processes, and inducing synaptic plasticity.Prog. Neurobiol. 1998; 55: 563-575Crossref PubMed Scopus (145) Google Scholar]. However, little work has been conducted at the cellular level to demonstrate that observed links between gamma oscillatory activity and STDP are specifically due to gamma oscillations matching the optimal timing constraints of STDP. This may be because the spiking delays necessary for STDP can vary across brain regions, cell types, and even between individual cells (Box 1). Consequently, a gamma oscillation of a precise frequency cannot match the timing delay of every cell in a network. However, it remains possible that gamma oscillations match the average preferred delay of the network, meaning that STDP-like phenomena could be reliable on a macroscopic (e.g., behavioural) level. In line with this idea, humans are better able to learn pairings between stimuli that rhythmically fluctuate in intensity (at 37.5 Hz) when, during the initial pairing, the cue preceded the target by ~7 ms (matching traditional STDP delays) relative to when the cue and target are presented simultaneously during encoding [15.Wang D. et al.Altering stimulus timing via fast rhythmic sensory stimulation induces STDP-like recall performance in human episodic memory.bioRxiv. 2022; (Published online November 3, 2022. https://doi.org/10.1101/2022.11.02.514843)Google Scholar]. Based on this finding, perhaps it is not a matter of ensuring that synapses of every neuron pair undergo STDP, but rather that sufficient pairs undergo STDP to ensure that a memory can be reliably formed.Box 1Variations on the traditional STDP curveThe textbook STDP curve depicts pre-to-postsynaptic firing inducing LTP, post-to-presynaptic firing inducing LTD, and the strength of the effects diminishing as the delay between the firing of the two neurons increases. Depictions of this curve are based on NMDA receptor-dependent STDP in slices of the rat hippocampus (e.g., [24.Bi G. Poo M. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type.J. Neurosci. 1998; 18: 1-9Crossref PubMed Google Scholar]), with the assumption that these curves generalise to other cells, brain regions, and even species. However, this may not be the case (Figure I).For example, GABAergic neurons fail to display LTP [24.Bi G. Poo M. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type.J. Neurosci. 1998; 18: 1-9Crossref PubMed Google Scholar] (and can even display LTD [134.Tzounopoulos T. et al.Cell-specific, spike timing-dependent plasticities in the dorsal cochlear nucleus.Nat. Neurosci. 2004; 7: 719-725Crossref PubMed Scopus (243) Google Scholar]) following pre-to-postsynaptic firing, suggesting that STDP curves vary based on cell type. In spiny stellate cells of the barrel cortex of rodents, pre-to-postsynaptic firing also induces LTD [135.Egger V. et al.Coincidence detection and changes of synaptic efficacy in spiny stellate neurons in rat barrel cortex.Nat. Neurosci. 1999; 2: 1098-1105Crossref PubMed Scopus (233) Google Scholar], hinting that STDP curves vary based on both brain regions and cell types. In human hippocampal tissue, LTP can be observed regardless of whether the presynaptic spike precedes or follows the postsynaptic spike, with LTD only being observed when the postsynaptic spike precedes the presynaptic spike by ~100 ms [30.Testa-Silva G. Human synapses show a wide temporal window for spike-timing-dependent plasticity.Front. Synaptic Neurosci. 2010; 2: 12PubMed Google Scholar], suggesting variation across species. Even in cells of the same type and region, STDP curves can vary simply because of variation in the distance between the soma and the location where input arrives on the dendrite: short distances produce the stereotypical curves, while greater distances invert the curve [136.Letzkus J.J. et al.Learning rules for spike timing-dependent plasticity depend on dendritic synapse location.J. Neurosci. 2006; 26: 10420-10429Crossref PubMed Scopus (221) Google Scholar]. Lastly, STDP curves of a single neuronal pair can vary based on the time difference between glutamate arriving at the NMDA receptor and the occurrence of a depolarising potential [137.Kampa B.M. et al.Kinetics of Mg2+ unblock of NMDA receptors: implications for spike-timing dependent synaptic plasticity.J. Physiol. 2004; 556: 337-345Crossref PubMed Scopus (142) Google Scholar]. In short, STDP curves can take many forms, and one should exercise caution when generalising STDP curves to other cells, brain regions, and species.This conclusion is also pertinent to the discussion of STDP and gamma oscillations: given that no two neurons are identical, it appears unlikely that there is a single oscillatory frequency that is optimal for enhancing STDP in all neurons. Indeed, variations in gamma oscillatory frequency across regions/species may well align with the differences in STDP curves that neurons in these regions/species exhibit. The textbook STDP curve depicts pre-to-postsynaptic firing inducing LTP, post-to-presynaptic firing inducing LTD, and the strength of the effects diminishing as the delay between the firing of the two neurons increases. Depictions of this curve are based on NMDA receptor-dependent STDP in slices of the rat hippocampus (e.g., [24.Bi G. Poo M. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type.J. Neurosci. 1998; 18: 1-9Crossref PubMed Google Scholar]), with the assumption that these curves generalise to other cells, brain regions, and even species. However, this may not be the case (Figure I). For example, GABAergic neurons fail to display LTP [24.Bi G. Poo M. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type.J. Neurosci. 1998; 18: 1-9Crossref PubMed Google Scholar] (and can even display LTD [134.Tzounopoulos T. et al.Cell-specific, spike timing-dependent plasticities in the dorsal cochlear nucleus.Nat. Neurosci. 2004; 7: 719-725Crossref PubMed Scopus (243) Google Scholar]) following pre-to-postsynaptic firing, suggesting that STDP curves vary based on cell type. In spiny stellate cells of the barrel cortex of rodents, pre-to-postsynaptic firing also induces LTD [135.Egger V. et al.Coincidence detection and changes of synaptic efficacy in spiny stellate neurons in rat barrel cortex.Nat. Neurosci. 1999; 2: 1098-1105Crossref PubMed Scopus (233) Google Scholar], hinting that STDP curves vary based on both brain regions and cell types. In human hippocampal tissue, LTP can be observed regardless of whether the presynaptic spike precedes or follows the postsynaptic spike, with LTD only being observed when the postsynaptic spike precedes the presynaptic spike by ~100 ms [30.Testa-Silva G. Human synapses show a wide temporal window for spike-timing-dependent plasticity.Front. Synaptic Neurosci. 2010; 2: 12PubMed Google Scholar], suggesting variation across species. Even in cells of the same type and region, STDP curves can vary simply because of variation in the distance between the soma and the location where input arrives on the dendrite: short distances produce the stereotypical curves, while greater distances invert the curve [136.Letzkus J.J. et al.Learning rules for spike timing-dependent plasticity depend on dendritic synapse location.J. Neurosci. 2006; 26: 10420-10429Crossref PubMed Scopus (221) Google Scholar]. Lastly, STDP curves of a single neuronal pair can vary based on the time difference between glutamate arriving at the NMDA receptor and the occurrence of a depolarising potential [137.Kampa B.M. et al.Kinetics of Mg2+ unblock of NMDA receptors: implications for spike-timing dependent synaptic plasticity.J. Physiol. 2004; 556: 337-345Crossref PubMed Scopus (142) Google Scholar]. In short, STDP curves can take many forms, and one should exercise caution when generalising STDP curves to other cells, brain regions, and species. This conclusion is also pertinent to the discussion of STDP and gamma oscillations: given that no two neurons are identical, it appears unlikely that there is a single oscillatory frequency that is optimal for enhancing STDP in all neurons. Indeed, variations in gamma oscillatory frequency across regions/species may well align with the differences in STDP curves that neurons in these regions/species exhibit. While the explanations explored in the preceding text suggest gamma oscillatory activity enhances STDP, they introduce an issue of firing order ambiguity. Specifically, if two neurons repeatedly and reliably fire as a function of gamma oscillatory phase, it becomes unclear which neuron leads which and, consequently, whether LTP or LTD will occur. In these instances, evidence suggests that LTP and LTD do not sum linearly [13.Sjöström P.J. et al.Rate, timing, and cooperativity jointly determine cortical synaptic plasticity.Neuron. 2001; 32: 1149-1164Abstract Full Text Full Text PDF PubMed Scopus (833) Google Scholar,38.Wang H.-X. et al.Coactivation and timing-dependent integration of synaptic potentiation and depression.Nat. Neurosci. 2005; 8: 187-193Crossref PubMed Scopus (233) Google Scholar,39.Froemke R.C. Dan Y. Spike-timing-dependent synaptic modification induced by natural spike trains.Nature. 2002; 416: 433-438Crossref PubMed Scopus (635) Google Scholar], with LTP possibly supplanting LTD [13.Sjöström P.J. et al.Rate, timing, and cooperativity jointly determine cortical synaptic plasticity.Neuron. 2001; 32: 1149-1164Abstract Full Text Full Text PDF PubMed Scopus (833) Google Scholar]. This suggests that the relevant timing of pre- and postsynaptic spikes becomes irrelevant so long as both neurons fire regularly and in quick succession. Consequently, ambiguity in firing order does not undermine the idea that gamma oscillations can enhance STDP. There is also the question of how gamma-facilitated plasticity scales up to the formation of fully fledged episodic memories. Unfortunately, linking gamma oscillations to both STDP and behavioural expressions of episodic memory in a single experiment is a troublesome endeavour: STDP is most easily observed in small cultures of cells and slice preparations, whereas behavioural expressions of episodic memory can only be observed in active individuals. That said, progress has been made. For example, in rodents, an increase in gamma oscillatory activity correlated with both an enhanced fear response to an auditory tone (i.e., a learned response) and a change in A1 receptive fields (a proxy for plasticity) [7.Headley D.B. Weinberger N.M. Gamma-band activation predicts both associative memory and cortical plasticity.J. Neurosci. 2011; 31: 12748-12758Crossref PubMed Scopus (51) Google Scholar]. Indirect links also exist in humans. For example, successful memory formation occurs when two conditions are met: (i) when the latency of firing between two neurons is ~20 ms (approximating the delay required for STDP); and (ii) when the co-firing neurons couple to an ongoing gamma oscillation [36.Roux F. et al.Oscillations support short latency co-firing of neurons during human episodic memory formation.eLife. 2022; 11e78109Crossref Scopus (3) Google Scholar]. This suggests that episodic memory formation is most probable when STDP-like delays in neuronal firing are coupled to an ongoing gamma oscillation. Together, these studies support the idea that gamma-facilitated STDP can lead to the formation of complex and highly detailed episodic memories. In sum, STDP is intimately tied to gamma oscillatory activity, although the mechanistic explanation of this link is open to debate. Moreover, it remains an open question whether gamma oscillations are necessary for STDP to occur. These questions may benefit from causal interventions that quantify the relevance of gamma oscillatory activity to STDP. Neural communication refers to the process of relaying information across the brain, be that between local cell assemblies or across large portions of the cortex. Neural communication is relevant to almost all aspects of cognition, from perception to action, but we focus here on its relevance to episodic memory. Effective neural communication ensures that, during memory formation, incoming information in sensory cortices activates the relevant cell assemblies in the hippocampus to ensure associative binding. Similarly, during retrieval, neural communication ensures that reactivated hippocampal cell assemblies induce neocortical activity to allow for the reinstatement of an episode. Here, we review key theories that link gamma oscillations to neural communication and assess whether they may, as a result, explain the link between gamma oscillatory activity and episodic memory. A prominent theory tying gamma activity to information exchange is 'communication through coherence' [40.Fries P. A mechanism for cognitive dynamics: neuronal communication through neuronal coherence.Trends Cogn. Sci. 2005; 9: 474-480Abstract Full Text Full Text PDF PubMed Scopus (2822) Google Scholar,41.Fries P. Rhythms for cognition: communication through coherence.Neuron. 2015; 88: 220-235Abstract Full Text Full Text PDF PubMed Scopus (1321) Google Scholar]. Communication through coherence proposes that information from one neural population can be relayed to another population when: (i) gamma