Fast-reset of pacemaking and theta-frequency resonance patterns in cerebellar golgi cells: Simulations of their impact in vivo

Grid cell spatial period is thought to be dictated by a mapping between the speed-direction modulated excitatory inputs, and consequent modulation of the firing rate, yet, the exact underlying mechanisms are not known. Here, through experiments on the medial entorhinal cortex stellate cells, subjected to in-vivo like stochastic synaptic activity through the dynamic clamp, we show that such mapping can emerge from a theta-frequency resonance in the signal gain, which is HCN sensitive, robust to noise, and is potent enough to modulate the synaptic responses in the theta frequency. This modulation also extends to the corresponding theta-gamma modulation of the firing rate, the slope of whose excitation mediated increase is steeper in the presence of HCN channels. We also show that in the cells devoid of HCN channels, inhibition can emulate their role. Considering the dorso-ventral gradients of HCN and inhibition, which are present aligned to the grid spacing gradient in the medial entorhinal cortex, these findings should be noteworthy.

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Theta-Frequency Resonance in Hippocampal CA1 Neurons In Vitro Demonstrated by Sinusoidal Current Injection

Journal of Neurophysiology ◽

10.1152/jn.1998.79.3.1592 ◽

1998 ◽

Vol 79 (3) ◽

pp. 1592-1596 ◽

Cited By ~ 108

Author(s):

L. Stan Leung ◽

Hui-Wen Yu

Keyword(s):

Resonant Frequency ◽

Hippocampal Neurons ◽

Ca1 Neurons ◽

Frequency Resonance ◽

Hippocampal Ca1 Neurons ◽

Hippocampal Ca1 ◽

Theta Frequency ◽

Sinusoidal Current ◽

Sinusoidal Currents

Leung, L. Stan and Hui-Wen Yu. Theta-frequency resonance in hippocampal CA1 neurons in vitro demonstrated by sinusoidal current injection. J. Neurophysiol. 79: 1592–1596, 1998. Sinusoidal currents of various frequencies were injected into hippocampal CA1 neurons in vitro, and the membrane potential responses were analyzed by cross power spectral analysis. Sinusoidal currents induced a maximal (resonant) response at a theta frequency (3–10 Hz) in slightly depolarized neurons. As predicted by linear systems theory, the resonant frequency was about the same as the natural (spontaneous) oscillation frequency. However, in some cases, the resonant frequency was higher than the spontaneous oscillation frequency, or resonance was found in the absence of spontaneous oscillations. The sharpness of the resonance ( Q), measured by the peak frequency divided by the half-peak power bandwidth, increased from a mean of 0.44 at rest to 0.83 during a mean depolarization of 6.5 mV. The phase of the driven oscillations changed most rapidly near the resonant frequency, and it shifted about 90° over the half-peak bandwidth of 8.4 Hz. Similar results were found using a sinusoidal function of slowly changing frequency as the input. Sinusoidal currents of peak-to-peak intensity of >100 pA may evoke nonlinear responses characterized by second and higher harmonics. The theta-frequency resonance in hippocampal neurons in vitro suggests that the same voltage-dependent phenomenon may be important in enhancing a theta-frequency response when hippocampal neurons are driven by medial septal or other inputs in vivo.

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Intrinsic Theta-Frequency Membrane Potential Oscillations in Hippocampal CA1 Interneurons of Stratum Lacunosum-Moleculare

Journal of Neurophysiology ◽

10.1152/jn.1999.81.3.1296 ◽

1999 ◽

Vol 81 (3) ◽

pp. 1296-1307 ◽

Cited By ~ 98

Author(s):

C. Andrew Chapman ◽

Jean-Claude Lacaille

Keyword(s):

Membrane Potential ◽

Hippocampal Slices ◽

Stratum Radiatum ◽

Potential Oscillations ◽

Spike Threshold ◽

Hippocampal Ca1 ◽

Theta Frequency ◽

Stratum Lacunosum Moleculare ◽

Membrane Potential Oscillations

Intrinsic theta-frequency membrane potential oscillations in hippocampal CA1 interneurons of stratum lacunosum-moleculare. The ionic conductances underlying membrane potential oscillations of hippocampal CA1 interneurons located near the border between stratum lacunosum-moleculare and stratum radiatum (LM) were investigated using whole cell current-clamp recordings in rat hippocampal slices. At 22°C, when LM cells were depolarized near spike threshold by current injection, 91% of cells displayed 2–5 Hz oscillations in membrane potential, which caused rhythmic firing. At 32°C, mean oscillation frequency increased to 7.1 Hz. Oscillations were voltage dependent and were eliminated by hyperpolarizing cells 6–10 mV below spike threshold. Blockade of ionotropic glutamate and GABA synaptic transmission did not affect oscillations, indicating that they were not synaptically driven. Oscillations were eliminated by tetrodotoxin, suggesting that Na+ currents generate the depolarizing phase of oscillations. Oscillations were not affected by blocking Ca2+ currents with Cd2+ or Ca2+-free ACSF or by blocking the hyperpolarization-activated current ( I h) with Cs+. Both Ba2+ and a low concentration of 4-aminopyridine (4-AP) reduced oscillations but TEA did not. Theta-frequency oscillations were much less common in interneurons located in stratum oriens. Intrinsic membrane potential oscillations in LM cells of the CA1 region thus involve an interplay between inward Na+ currents and outward K+ currents sensitive to Ba2+ and 4-AP. These oscillations may participate in rhythmic inhibition and synchronization of pyramidal neurons during theta activity in vivo.

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Optogenetic activation of SST-positive interneurons restores hippocampal theta oscillation impairment induced by soluble amyloid beta oligomersin vivo

10.1101/465112 ◽

2018 ◽

Author(s):

Hyowon Chung ◽

Kyerl Park ◽

Hyun Jae Jang ◽

Michael M Kohl ◽

Jeehyun Kwag

Keyword(s):

Learning And Memory ◽

Peak Power ◽

Pyramidal Neurons ◽

Hippocampal Slices ◽

Field Potential ◽

Theta Oscillations ◽

Ca1 Pyramidal Neurons ◽

Theta Frequency ◽

Hippocampal Theta

AbstractAbnormal accumulation of amyloid β oligomers (AβO) is a hallmark of Alzheimer’s disease (AD), which leads to learning and memory deficits. Hippocampal theta oscillations that are critical in spatial navigation, learning and memory are impaired in AD. Since GABAergic interneurons, such as somatostatin-positive (SST+) and parvalbumin-positive (PV+) interneurons, are believed to play key roles in the hippocampal oscillogenesis, we asked whether AβO selectively impairs these SST+ and PV+ interneurons. To selectively manipulate SST+ or PV+ interneuron activity in mice with AβO pathologyin vivo, we co-injected AβO and adeno-associated virus (AAV) for expressing floxed channelrhodopsin-2 (ChR2) into the hippocampus of SST-Cre or PV-Cre mice. Local field potential (LFP) recordingsin vivoin these AβO–injected mice showed a reduction in the peak power of theta oscillations and desynchronization of spikes from CA1 pyramidal neurons relative to theta oscillations compared to those in control mice. Optogenetic-activation of SST+ but not PV+ interneurons in AβO–injected mice fully restored the peak power of theta oscillations and resynchronized the theta spike phases to a level observed in control mice.In vitrowhole-cell voltage-clamp recordings in CA1 pyramidal neurons in hippocampal slices treated with AβO revealed that short-term plasticity of SST+ interneuron inhibitory inputs to CA1 pyramidal neurons at theta frequency were selectively disrupted while that of PV+ interneuron inputs were unaffected. Together, our results suggest that dysfunction in inputs from SST+ interneurons to CA1 pyramidal neurons may underlie the impairment of theta oscillations observed in AβO-injected micein vivo.Our findings identify SST+ interneurons as a target for restoring theta-frequency oscillations in early AD.

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Deciphering how interneuron specific 3 cells control oriens lacunosum-moleculare cells to contribute to circuit function

Journal of Neurophysiology ◽

10.1152/jn.00204.2021 ◽

2021 ◽

Author(s):

Alexandre Guet-McCreight ◽

Frances K Skinner

Keyword(s):

Pyramidal Cell ◽

Inhibitory Interneuron ◽

Cell Type ◽

Cell Recruitment ◽

External Modulation ◽

Theta Frequency ◽

Cell Firing ◽

Circuit Function

The wide diversity of inhibitory cells across the brain makes them suitable to contribute to network dynamics in specialized fashions. However, the contributions of a particular inhibitory cell type in a behaving animal are challenging to untangle as one needs to both record cellular activities and identify the cell type being recorded. Thus, using computational modeling and theory to predict and hypothesize cell-specific contributions is desirable. Here, we examine potential contributions of interneuron-specific 3 (I-S3) cells - an inhibitory interneuron found in CA1 hippocampus that only targets other inhibitory interneurons - during simulated theta rhythms. We use previously developed multi-compartment models of oriens lacunosum-moleculare (OLM) cells, the main target of I-S3 cells, and explore how I-S3 cell inputs during in vitro and in vivo scenarios contribute to theta. We find that I-S3 cells suppress OLM cell spiking, rather than engender its spiking via post-inhibitory rebound mechanisms, and contribute to theta frequency spike resonance during simulated in vivo scenarios. To elicit recruitment similar to in vitro experiments, inclusion of disinhibited pyramidal cell inputs is necessary, implying that I-S3 cell firing broadens the window for pyramidal cell disinhibition. Using in vivo virtual networks, we show that I-S3 cells contribute to a sharpening of OLM cell recruitment at theta frequencies. Further, shifting the timing of I-S3 cell spiking due to external modulation shifts the timing of the OLM cell firing and thus disinhibitory windows. We propose a specialized contribution of I-S3 cells to create temporally precise coordination of modulation pathways.

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Theta-Frequency Resonance at the Cerebellum Input Stage Improves Spike Timing on the Millisecond Time-Scale

Frontiers in Neural Circuits ◽

10.3389/fncir.2013.00064 ◽

2013 ◽

Vol 7 ◽

Cited By ~ 26

Author(s):

Daniela Gandolfi ◽

Paola Lombardo ◽

Jonathan Mapelli ◽

Sergio Solinas ◽

Egidio D’Angelo

Keyword(s):

Time Scale ◽

Spike Timing ◽

Input Stage ◽

Frequency Resonance ◽

Theta Frequency ◽

Millisecond Time Scale

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Endocannabinoids regulate mAChR-evoked theta rhythm IPSCs in hippocampus

10.1101/022442 ◽

2015 ◽

Author(s):

Ai-Hui Tang ◽

Daniel A Nagode ◽

Bradley E Alger

Keyword(s):

Theta Rhythm ◽

Cannabinoid Receptor ◽

Spectral Power ◽

Hippocampal Slices ◽

Ionotropic Glutamate Receptors ◽

Frequency Range ◽

Neuronal Oscillations ◽

Theta Frequency ◽

Endogenous Cannabinoids

Exogenous cannabinoids can affect behaviorally relevant neuronal oscillations, but there is little evidence that endogenous cannabinoids (endocannabinoids, eCBs) can affect them, although it is unknown whether eCBs were generated during oscillations investigated in previous studies. In rat hippocampal slices, muscarinic receptor (mAChR) agonists stimulate the occurrence of persistent, rhythmic inhibitory post-synaptic currents (IPSC) activity and mobilize eCBs. We tested the hypothesis that mAChR-induced IPSCs would be modulated by concomitantly produced eCBs. With ionotropic glutamate receptors inhibited, mAChR agonist application triggered eCB-sensitive IPSCs that were enhanced in amplitude and frequency when a cannabinoid receptor antagonist was also present. There was also a highly significant increase in IPSC spectral power in the theta-frequency range. The data show that eCBs released by mAChRs modulate rhythmic IPSCs, and suggest that eCBs are candidate regulators of neuronal oscillations associated with eCB production in vivo.

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Hippocampal rhythm generation: Gamma-related theta-frequency resonance in CA3 interneurons

Biological Cybernetics ◽

10.1007/s004220000199 ◽

2001 ◽

Vol 84 (2) ◽

pp. 123-132 ◽

Cited By ~ 23

Author(s):

G. Orbán ◽

T. Kiss ◽

M. Lengyel ◽

P. Érdi

Keyword(s):

Rhythm Generation ◽

Frequency Resonance ◽

Theta Frequency

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Intrinsic and Synaptic Mechanisms Determining the Timing of Neuron Population Activity During Hippocampal Theta Oscillation

Journal of Neurophysiology ◽

10.1152/jn.01233.2005 ◽

2006 ◽

Vol 96 (6) ◽

pp. 2889-2904 ◽

Cited By ~ 31

Author(s):

Gergő Orbán ◽

Tamás Kiss ◽

Péter Érdi

Keyword(s):

Metabotropic Glutamate Receptors ◽

Pyramidal Cells ◽

Neuron Population ◽

Population Activity ◽

Theta Oscillation ◽

Hippocampal Ca1 ◽

Theta Frequency ◽

Hippocampal Theta

Hippocampal theta (3–8 Hz) is a major electrophysiological activity in rodents, which can be found in primates and humans as well. During theta activity, pyramidal cells and different classes of interneurons were shown to discharge at different phases of the extracellular theta. A recent in vitro study has shown that theta-frequency oscillation can be elicited in a hippocampal CA1 slice by the activation of metabotropic glutamate receptors with similar pharmacological and physiological profile that was found in vivo. We constructed a conductance based three-population network model of the hippocampal CA1 region to study the specific roles of neuron types in the generation of the in vitro theta oscillation and the emergent network properties. Interactions between pairs of neuron populations were studied systematically to assess synchronization and delay properties. We showed that the circuitry consisting of pyramidal cells and two types of hippocampal interneurons [basket and oriens lacunosum-moleculare (O-LM) neurons] was able to generate coherent theta-frequency population oscillation. Furthermore, we found that hyperpolarization-activated nonspecific cation current in pyramidal cells, but not in O-LM neurons, plays an important role in the timing of spike generation, and thus synchronization of pyramidal cells. The model was shown to exhibit the same phase differences between neuron population activities found in vivo, supporting the idea that these patterns of activity are determined internal to the hippocampus.

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Bidirectional propagation of low frequency oscillations over the human hippocampal surface

Nature Communications ◽

10.1038/s41467-021-22850-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jonathan K. Kleen ◽

Jason E. Chung ◽

Kristin K. Sellers ◽

Jenny Zhou ◽

Michael Triplett ◽

...

Keyword(s):

Low Frequency ◽

Low Frequency Oscillations ◽

Spatiotemporal Processing ◽

Propagation Axis ◽

Theta Frequency ◽

Temporal Pole ◽

Scale Network ◽

Bidirectional Propagation ◽

Oscillation Frequencies

AbstractThe hippocampus is diversely interconnected with other brain systems along its axis. Cycles of theta-frequency activity are believed to propagate from the septal to temporal pole, yet it is unclear how this one-way route supports the flexible cognitive capacities of this structure. We leveraged novel thin-film microgrid arrays conformed to the human hippocampal surface to track neural activity two-dimensionally in vivo. All oscillation frequencies identified between 1–15 Hz propagated across the tissue. Moreover, they dynamically shifted between two roughly opposite directions oblique to the long axis. This predominant propagation axis was mirrored across participants, hemispheres, and consciousness states. Directionality was modulated in a participant who performed a behavioral task, and it could be predicted by wave amplitude topography over the hippocampal surface. Our results show that propagation directions may thus represent distinct meso-scale network computations, operating along versatile spatiotemporal processing routes across the hippocampal body.

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