Cell Type-Specific Firing during Ripple Oscillations in the Hippocampal Formation of Humans

Centre National de la Recherche Scientifique, Cognitive Neuroscience and Brain Imaging Laboratory, Unité Propre de Recherche 640, Hôpital de la Pitié-Salpêtrière, 75651 Paris, France.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 07/2008; 28(24):6104-10. DOI: 10.1523/JNEUROSCI.0437-08.2008
Source: PubMed


High-frequency field ripples occur in the rodent hippocampal formation and are assumed to depend on interneuron type-specific firing patterns, structuring the activity of pyramidal cells. Ripples with similar characteristics are also present in humans, yet their underlying cellular correlates are still unknown. By in vivo recording interneurons and pyramidal cells in the human hippocampal formation, we find that cell type-specific firing patterns and phase-locking on a millisecond timescale can be distinguished during ripples. In particular, pyramidal cells fired preferentially at the highest amplitude of the ripple, but interneurons began to discharge earlier than pyramidal cells. Furthermore, a large fraction of cells were phase-locked to the ripple cycle, but the preferred phase of discharge of interneurons followed the maximum discharge probability of pyramidal neurons. These relationships between human ripples and unit activity are qualitatively similar to that observed in vivo in the rodents, suggesting that their underlying mechanisms are similar.

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Available from: Anatol Bragin, Oct 13, 2015
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    • "In patient studies and chronic animal models of epilepsy, there appear to be different types of HFOs with some that have properties that strongly resemble 100–200 Hz ripples in the normal nonprimate and nonhuman primate hippocampal formation (Axmacher, Elger, & Fell, 2008; Bragin, Engel, Wilson, Vizentin, & Mathern, 1999; Buzsaki, 1998; Le Van Quyen et al., 2008; Skaggs et al., 2007; Staba, Wilson, Bragin, Fried, & "
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    ABSTRACT: Limbic epilepsy refers to a condition that consists of epileptic seizures that originate in or preferentially involve the limbic system. The majority of cases are medically refractory, necessitating surgical resection when possible. However, even resection of structures thought to be responsible for seizure generation may not leave a patient seizure free. While mesial temporal lobe limbic structures are centrally involved, there is growing evidence that the epileptogenic network consists of a broader area, involving structures outside of the temporal lobe and the limbic system. Information on structural, functional, and metabolic connectivity in patients with limbic epilepsy is available from a large body of studies employing methods such as MRI, EEG, MEG, fMRI, PET, and SPECT scanning, implicating the involvement of various brain regions in the epileptogenic network. To date, there are no consistent and conclusive findings to define the exact boundaries of this network, but it is possible that in the future studies of network connectivity in the individual patient may allow more tailored treatment and prognosis in terms of surgical resection.
    International Review of Neurobiology 08/2014; 114C:89-120. DOI:10.1016/B978-0-12-418693-4.00005-4 · 1.92 Impact Factor
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    • "Selective elimination of ripples during postlearning results in impairment of memory performance (Girardeau et al., 2009; Jadhav et al., 2012). Despite the critical role of ripples for information transfer from the hippocampus to the neocortex and for memory consolidation, and their postulated role in epilepsy (''fast ripples''; Bragin et al., 1999; Le Van Quyen et al., 2008), the local network mechanisms underlying the generation of ripples are not well understood (Buzsá ki and Silva, 2012). Three classes of models for ripple generation have been proposed . "
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    ABSTRACT: High-frequency ripple oscillations, observed most prominently in the hippocampal CA1 pyramidal layer, are associated with memory consolidation. The cellular and network mechanisms underlying the generation, frequency control, and spatial coherence of the rhythm are poorly understood. Using multisite optogenetic manipulations in freely behaving rodents, we found that depolarization of a small group of nearby pyramidal cells was sufficient to induce high-frequency oscillations, whereas closed-loop silencing of pyramidal cells or activation of parvalbumin- (PV) or somatostatin-immunoreactive interneurons aborted spontaneously occurring ripples. Focal pharmacological blockade of GABAA receptors abolished ripples. Localized PV interneuron activation paced ensemble spiking, and simultaneous induction of high-frequency oscillations at multiple locations resulted in a temporally coherent pattern mediated by phase-locked interneuron spiking. These results constrain competing models of ripple generation and indicate that temporally precise local interactions between excitatory and inhibitory neurons support ripple generation in the intact hippocampus.
    Neuron 07/2014; 83(2):467–480. DOI:10.1016/j.neuron.2014.06.023 · 15.05 Impact Factor
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    • "In particular, the authors of those reports have shown that, like in the case of the rodent sharp-wave ripple complexes, units coordinated their firing to specific phase of ripple HFO cycle in humans, during which interneurons fired before pyramidal cells. The neuronal correlates of induced ripples and fast ripples, or cortical HFOs remain to be explored but given the evidence from human (Le Van Quyen et al., 2008, 2010) and rodent studies (Sullivan et al., 2011) they could share similar networks and mechanisms. "
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    ABSTRACT: High frequency oscillations are associated with normal brain function, but also increasingly recognized as potential biomarkers of the epileptogenic brain. Their role in human cognition has been predominantly studied in classical gamma frequencies (30-100 Hz), which reflect neuronal network coordination involved in attention, learning and memory. Invasive brain recordings in animals and humans demonstrate that physiological oscillations extend beyond the gamma frequency range, but their function in human cognitive processing has not been fully elucidated. Here we investigate high frequency oscillations spanning the high gamma (50-125 Hz), ripple (125-250 Hz) and fast ripple (250-500 Hz) frequency bands using intracranial recordings from 12 patients (five males and seven females, age 21-63 years) during memory encoding and recall of a series of affectively charged images. Presentation of the images induced high frequency oscillations in all three studied bands within the primary visual, limbic and higher order cortical regions in a sequence consistent with the visual processing stream. These induced oscillations were detected on individual electrodes localized in the amygdala, hippocampus and specific neocortical areas, revealing discrete oscillations of characteristic frequency, duration and latency from image presentation. Memory encoding and recall significantly modulated the number of induced high gamma, ripple and fast ripple detections in the studied structures, which was greater in the primary sensory areas during the encoding (Wilcoxon rank sum test, P = 0.002) and in the higher-order cortical association areas during the recall (Wilcoxon rank sum test, P = 0.001) of memorized images. Furthermore, the induced high gamma, ripple and fast ripple responses discriminated the encoded and the affectively charged images. In summary, our results show that high frequency oscillations, spanning a wide range of frequencies, are associated with memory processing and generated along distributed cortical and limbic brain regions. These findings support an important role for fast network synchronization in human cognition and extend our understanding of normal physiological brain activity during memory processing.
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