The consolidation of spatial memory depends on the reactivation ('replay') of hippocampal place cells that were active during recent behaviour. Such reactivation is observed during sharp-wave ripples ...(SWRs)-synchronous oscillatory electrical events that occur during non-rapid-eye-movement (non-REM) sleep
and whose disruption impairs spatial memory
. Although the hippocampus also encodes a wide range of non-spatial forms of declarative memory, it is not yet known whether SWRs are necessary for such memories. Moreover, although SWRs can arise from either the CA3 or the CA2 region of the hippocampus
, the relative importance of SWRs from these regions for memory consolidation is unknown. Here we examine 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-focusing on CA2 because of its essential role in social memory
. We find that ensembles of CA2 pyramidal neurons that are active during social exploration of previously unknown conspecifics are reactivated during SWRs. Notably, disruption or enhancement of CA2 SWRs suppresses or prolongs social memory, respectively. Thus, SWR-mediated reactivation of hippocampal firing related to recent experience appears to be a general mechanism for binding spatial, temporal and sensory information into high-order memory representations, including social memory.
Sharp-wave ripples (SPW-Rs) in the hippocampus are implied in memory consolidation, as shown by observational and interventional experiments. However, the mechanism of their generation remains ...unclear. Using two-dimensional silicon probe arrays, we investigated the propagation of SPW-Rs across the hippocampal CA1, CA2, and CA3 subregions. Synchronous activation of CA2 ensembles preceded SPW-R-related population activity in CA3 and CA1 regions. Deep CA2 neurons gradually increased their activity prior to ripples and were suppressed during the population bursts of CA3-CA1 neurons (ramping cells). Activity of superficial CA2 cells preceded the activity surge in CA3-CA1 (phasic cells). The trigger role of the CA2 region in SPW-R was more pronounced during waking than sleeping. These results point to the CA2 region as an initiation zone for SPW-Rs.
•Synchronous activity in CA2 region precedes sharp-wave ripples (SPW-Rs).•Activity of deep CA2 pyramidal cells ramps up before SPW-R, then quickly drops•Superficial CA2 cells fire synchronously preceding CA3 and CA1 during SPW-Rs•CA2 cells contribute more strongly to WAKE SPW-Rs while CA3 participates more in SLEEP
Oliva et al. show that sharp-wave ripple (SPW-R) related activation of CA2 neurons precede those in CA3 and CA1. Deep CA2 cells gradually increase their activity prior to SPW-Rs, establishing the CA2 region as a potential trigger for SPW-R generation.
Long-duration hippocampal sharp wave ripples improve memory Fernández-Ruiz, Antonio; Oliva, Azahara; Fermino de Oliveira, Eliezyer ...
Science (American Association for the Advancement of Science),
06/2019, Letnik:
364, Številka:
6445
Journal Article
Recenzirano
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Hippocampal sharp wave ripples (SPW-Rs) have been hypothesized as a mechanism for memory consolidation and action planning. The duration of ripples shows a skewed distribution with a minority of ...long-duration events. We discovered that long-duration ripples are increased in situations demanding memory in rats. Prolongation of spontaneously occurring ripples by optogenetic stimulation, but not randomly induced ripples, increased memory during maze learning. The neuronal content of randomly induced ripples was similar to short-duration spontaneous ripples and contained little spatial information. The spike content of the optogenetically prolonged ripples was biased by the ongoing, naturally initiated neuronal sequences. Prolonged ripples recruited new neurons that represented either arm of the maze. Long-duration hippocampal SPW-Rs replaying large parts of planned routes are critical for memory.
Transcranial electric stimulation is a non-invasive tool that can influence brain activity; however, the parameters necessary to affect local circuits in vivo remain to be explored. Here, we report ...that in rodents and human cadaver brains, ~75% of scalp-applied currents are attenuated by soft tissue and skull. Using intracellular and extracellular recordings in rats, we find that at least 1 mV/mm voltage gradient is necessary to affect neuronal spiking and subthreshold currents. We designed an 'intersectional short pulse' stimulation method to inject sufficiently high current intensities into the brain, while keeping the charge density and sensation on the scalp surface relatively low. We verify the regional specificity of this novel method in rodents; in humans, we demonstrate how it affects the amplitude of simultaneously recorded EEG alpha waves. Our combined results establish that neuronal circuits are instantaneously affected by intensity currents that are higher than those used in conventional protocols.
Gamma oscillations are thought to coordinate the spike timing of functionally specialized neuronal ensembles across brain regions. To test this hypothesis, we optogenetically perturbed gamma spike ...timing in the rat medial (MEC) and lateral (LEC) entorhinal cortices and found impairments in spatial and object learning tasks, respectively. MEC and LEC were synchronized with the hippocampal dentate gyrus through high- and low-gamma-frequency rhythms, respectively, and engaged either granule cells or mossy cells and CA3 pyramidal cells in a task-dependent manner. Gamma perturbation disrupted the learning-induced assembly organization of target neurons. Our findings imply that pathway-specific gamma oscillations route task-relevant information between distinct neuronal subpopulations in the entorhinal-hippocampal circuit. We hypothesize that interregional gamma-time-scale spike coordination is a mechanism of neuronal communication.
In understanding circuit operations, a key problem is the extent to which neuronal spiking reflects local computation or responses to upstream inputs. We addressed this issue in the hippocampus by ...performing combined optogenetic and pharmacogenetic local and upstream inactivation. Silencing the medial entorhinal cortex (mEC) largely abolished extracellular theta and gamma currents in CA1 while only moderately affecting firing rates. In contrast, CA3 and local CA1 silencing strongly decreased firing of CA1 neurons without affecting theta currents. Each perturbation reconfigured the CA1 spatial map. However, the ability of the CA1 circuit to support place field activity persisted, maintaining the same fraction of spatially tuned place fields and reliable assembly expression as in the intact mouse. Thus, the CA1 network can induce and maintain coordinated cell assemblies with minimal reliance on its inputs, but these inputs can effectively reconfigure and assist in maintaining stability of the CA1 map.
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•Unilateral or bilateral silencing of the mEC decreases theta and gamma currents•Bilateral but not unilateral mEC silencing causes remapping in CA1 cell assemblies•CA3 silencing decreases CA1 firing rates and leads to place cell remapping•CA1 place cells and assemblies persist despite combined mEC and CA3 silencing
Zutshi et al. perform simultaneous silencing of major afferents into the hippocampal CA1 to address whether CA1 spiking can be sustained by local computations. These manipulations reveal that coordinated CA1 place cell assemblies persist with minimal input but that each input has distinct effects on spatial tuning and field potentials.
Theta-gamma phase coupling and spike timing within theta oscillations are prominent features of the hippocampus and are often related to navigation and memory. However, the mechanisms that give rise ...to these relationships are not well understood. Using high spatial resolution electrophysiology, we investigated the influence of CA3 and entorhinal inputs on the timing of CA1 neurons. The theta-phase preference and excitatory strength of the afferent CA3 and entorhinal inputs effectively timed the principal neuron activity, as well as regulated distinct CA1 interneuron populations in multiple tasks and behavioral states. Feedback potentiation of distal dendritic inhibition by CA1 place cells attenuated the excitatory entorhinal input at place field entry, coupled with feedback depression of proximal dendritic and perisomatic inhibition, allowing the CA3 input to gain control toward the exit. Thus, upstream inputs interact with local mechanisms to determine theta-phase timing of hippocampal neurons to support memory and spatial navigation.
•Cooperation of entorhinal and CA3 inputs controls spike timing of hippocampal neurons•Phase precession is under dual entorhinal and CA3 control•Spike timing in REM and learning depends on the strengths of upstream gamma inputs•Feedback inhibition is layer specific and varies within place fields
Fernández-Ruiz et al. provide evidence that the phase-precession phenomenon is part of a larger family of spike timing mechanisms and provide a common explanation for all of them. Cooperation of CA3 and entorhinal gamma inputs, together with local inhibition, determines spike timing.
Precisely how rhythms support neuronal communication remains obscure. We investigated interregional coordination of gamma oscillations using high-density electrophysiological recordings in the rat ...hippocampus and entorhinal cortex. We found that 30–80 Hz gamma dominated CA1 local field potentials (LFPs) on the descending phase of CA1 theta waves during navigation, with 60–120 Hz gamma at the theta peak. These signals corresponded to CA3 and entorhinal input, respectively. Above 50 Hz, interregional phase-synchronization of principal cell spikes occurred mostly for LFPs in the axonal target domain. CA1 pyramidal cells were phase-locked mainly to fast gamma (>100 Hz) LFP patterns restricted to CA1, which were strongest at the theta trough. While theta phase coordination of spiking across entorhinal-hippocampal regions depended on memory demands, LFP gamma patterns below 100 Hz in the hippocampus were consistently layer specific and largely reflected afferent activity. Gamma synchronization as a mechanism for interregional communication thus rapidly loses efficacy at higher frequencies.
•CA1 dendritic layer gamma rhythms reflect driving afferent patterns•CA3 input to CA1 typically occurs later in the theta cycle than EC input•CA1 output patterns are not coherently entrained by fast input rhythms•CA1 pyramidal cell activity is locally coordinated at high frequencies
How brain rhythms support information exchange remains obscure. Schomburg et al. employ large-scale electrophysiological recordings in the hippocampus and entorhinal cortex of behaving rats to investigate the coordination and synchrony of gamma oscillations within and between regions.
Using clever experimental design and exploiting the high temporal resolution power of magnetoencephalography, Liu et al. show in humans how “offline” reactivation of brain patterns allows the ...abstraction of new knowledge from previous experience. The key mechanism may involve hippocampal sharp-wave ripples.
Using clever experimental design and exploiting the high temporal resolution power of magnetoencephalography, Liu et al. show in humans how “offline” reactivation of brain patterns allows the abstraction of new knowledge from previous experience. The key mechanism may involve hippocampal sharp-wave ripples.
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