Gamma Oscillatory Firing Reveals Distinct Populations of Pyramidal Cells in the CA1 Region of the Hippocampus

357

315

Hippocampal theta (5-10 Hz) and gamma (35-85 Hz) oscillations depend on an inhibitory network of GABAergic interneurons. However, the lack of methods for direct and cell-type-specific interference with inhibition has prevented better insights that help link synaptic and cellular properties with network function. Here, we generated genetically modified mice (PV-⌬␥ 2) in which synaptic inhibition was ablated in parvalbumin-positive (PV؉) interneurons. Hippocampal local field potential and unit recordings in the CA1 area of freely behaving mice revealed that theta rhythm was strongly reduced in these mice. The characteristic coupling of theta and gamma oscillations was strongly altered in PV-⌬␥ 2 mice more than could be accounted for by the reduction in theta rhythm only. Surprisingly, gamma oscillations were not altered. These data indicate that synaptic inhibition onto PV؉ interneurons is indispensable for theta-and its coupling to gamma oscillations but not for rhythmic gammaactivity in the hippocampus. Similar alterations in rhythmic activity were obtained in a computational hippocampal network model mimicking the genetic modification, suggesting that intrahippocampal networks might contribute to these effects.compartmental model ͉ GABA ͉ GABAA receptor ͉ knockout ͉ network synchrony

Section: Discussionmentioning

confidence: 94%

“…Here, the power (or amplitude) of the gamma oscillations is systematically modulated (coupled) during each theta cycle. Such cross-frequency coupling may aid the execution of cognitive functions such as working memory (10)(11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

Hippocampal theta rhythm and its coupling with gamma oscillations require fast inhibition onto parvalbumin-positive interneurons

Wulff

Ponomarenko²,

Bartos

et al. 2009

357

315

“…In animals, action potentials firing with respect to specific phases of ongoing theta oscillations accompany the encoding of sequences of spatial positions (11). In addition, firing rate is modulated by the phase of gamma band activity (12,13). A related phase code based on interactions of theta phase and gamma oscillations has been suggested to support maintenance of multiple items in WM (14,15).…”

mentioning

confidence: 99%

Cross-frequency coupling supports multi-item working memory in the human hippocampus

Axmacher

Henseler

Jensen³

et al. 2010

821

757

Recent findings indicate that the hippocampus supports not only longterm memory encoding but also plays a role in working memory (WM) maintenance of multiple items; however, the neural mechanism underlying multi-item maintenance is still unclear. Theoretical work suggests that multiple items are being maintained by neural assemblies synchronized in the gamma frequency range (25-100 Hz) that are locked to consecutive phase ranges of oscillatory activity in the theta frequency range (4-8 Hz). Indeed, cross-frequency coupling of the amplitude of high-frequency activity to the phase of slower oscillations has been described both in animals and in humans, but has never been linked to a theoretical model of a cognitive process. Here we used intracranial EEG recordings in human epilepsy patients to test pivotal predictions from theoretical work. First, we show that simultaneous maintenance of multiple items in WM is accompanied by cross-frequency coupling of oscillatory activity in the hippocampus, which is recruited during multiitem WM. Second, maintenance of an increasing number of items is associated with modulation of beta/gamma amplitude with theta band activity of lower frequency, consistent with the idea that longer cycles are required for an increased number of representations by gamma cycles. This effect cannot be explained by a difference in theta or beta/ gamma power. Third, we describe how the precision of cross-frequency coupling predicts individual WM performance. These data support the idea that working memory in humans depends on a neural code using phase information. W orking memory (WM), the ability to maintain information about multiple items over a short time span, is indispensable for goal-directed behavior (1). Precise synchronization of neurons and neural networks results in oscillatory activity patterns in the gamma frequency range (25-100 Hz) and serves to facilitate neural communication and memory processing (2, 3). Data from animals and humans provide evidence that sustained increases of high-frequency activity (4-7) and theta (4-8 Hz) oscillations (8-10) are a neural correlate of WM maintenance. However, how multiple items can be simultaneously maintained without interference remains unknown. In animals, action potentials firing with respect to specific phases of ongoing theta oscillations accompany the encoding of sequences of spatial positions (11). In addition, firing rate is modulated by the phase of gamma band activity (12, 13). A related phase code based on interactions of theta phase and gamma oscillations has been suggested to support maintenance of multiple items in WM (14,15). Such crossfrequency coupling has been described in rodents (16,17) and recently in the human brain (18,19), but its link to multi-item WM has not been investigated.Here we address the question of whether multiple items are encoded by modulation of the amplitude of high-frequency oscillations by the phase of oscillations in a lower-frequency range in the human hippocampus. We used a modified Sternberg paradigm...

“…Thus, it has been proposed that memory sequences can be encoded by the firing patterns of cells in successive gamma cycles nested within each theta cycle (16). Recently, it was revealed in the hippocampus of behaving animals that gamma-related firing during theta oscillations can support the formation of such a temporal code (17). However, 2 distinct populations of hippocampal principal cells were differentiated in the CA1 region, representing movement trajectories and places, which each support different types of population codes within a theta cycle.…”

mentioning

confidence: 99%

Inhibitory interneurons and network oscillations

Dupret

Pleydell-Bouverie

Csicsvari

2008

N euronal networks in the brain oscillate in various frequency bands, and such oscillations can be detected by observing local field potential or EEG activity (1). Oscillations in the gamma frequency band (30-80 Hz) have drawn special attention because of their link to a variety of cognitive processes including sensory binding (2), attention selection (3), and memory (4, 5). Of particular physiological interest are questions of how gamma oscillations are generated and synchronized across brain regions. The study by Middleton et al. in this issue of PNAS (6) provides novel insights into these questions: it identifies 2 subcircuits within the entorhinal cortex (EC) that are capable of generating gamma oscillations at different frequencies. Moreover, it presents data implying that these generators recruit different neuronal pathways in their communication with the hippocampus. Their study points out for the first time the specialized role of inhibitory interneuron types in generating oscillatory patterns at different frequencies. Given that both the hippocampo-EC system and gamma oscillations are linked to memory processing, the temporal interactions between the EC and the hippocampus at these distinct gamma frequencies could be involved in different aspects of mnemonic processes.The report by Middleton et al. (6) examines the mechanism behind how gamma oscillations are generated in the EC with an emphasis on the effect of the NMDA receptor activation: a key glutamatergic receptor for synaptic plasticity and memory formation. Using an in vitro preparation of the EC, they demonstrate that gamma oscillations slow down when NMDA receptors (NMDARs) are blocked by ketamine (an NMDAR antagonist). They then show that NMDA-dependent (fast, Ϸ40 Hz) and NMDA-independent (slow, Ϸ30 Hz) gamma rhythms are generated by functionally distinct subcircuits (Fig.