Intrinsic Cornu Ammonis Area 1 Theta-Nested Gamma Oscillations Induced by Optogenetic Theta Frequency Stimulation

Abstract

Gamma oscillations (30 -120 Hz) are thought to be important for various cognitive functions, including perception and working memory, and disruption of these oscillations has been implicated in brain disorders, such as schizophrenia and Alzheimer's disease. The cornu ammonis area 1 (CA1) of the hippocampus receives gamma frequency inputs from upstream regions (cornu ammonis area 3 and medial entorhinal cortex) and generates itself a faster gamma oscillation. The exact nature and origin of the intrinsic CA1 gamma oscillation is still under debate. Here, we expressed channelrhodopsin-2 under the CaMKII␣ promoter in mice and prepared hippocampal slices to produce a model of intrinsic CA1 gamma oscillations. Sinusoidal optical stimulation of CA1 at theta frequency was found to induce robust theta-nested gamma oscillations with a temporal and spatial profile similar to CA1 gamma in vivo. The results suggest the presence of a single gamma rhythm generator with a frequency range of 65-75 Hz at 32°C. Pharmacological analysis found that the oscillations depended on both AMPA and GABA A receptors. Cell-attached and whole-cell recordings revealed that excitatory neuron firing slightly preceded interneuron firing within each gamma cycle, suggesting that this intrinsic CA1 gamma oscillation is generated with a pyramidal-interneuron circuit mechanism.

Altered Oscillatory Dynamics of CA1 Parvalbumin Basket Cells during Theta–Gamma Rhythmopathies of Temporal Lobe Epilepsy

“…Recently, Schomburg et al (2014) showed that local hippocampal theta–gamma coupling at 30–60 Hz is more prominent at the proximal CA1, where GABAergic interneurons are strongly driven by Schaffer collaterals (Oliva et al, 2016). Both in epileptic and control rats, slow gamma oscillations were in phase with CSD sinks at the SR, which is consistent with this feedforward activation model (Mann et al, 2005; Zemankovics et al, 2013; Butler et al, 2016). PV basket cell firing at the falling theta phase have been involved in the mechanism (Lasztóczi and Klausberger, 2014).…”

“…An intrahippocampal slow gamma generator (30–60 Hz) operates at the falling phase of theta coincident with CA3 Schaffer inputs arriving at the stratum radiatum (SR; Csicsvari et al, 2003; Lasztóczi and Klausberger, 2014). A third, even faster, generator (>100 Hz) runs locally at SP during the negative peak of theta when CA1 pyramidal cells (PCs) fire maximally (Schomburg et al, 2014; Butler et al, 2016). A detailed proximodistal arrangement along the hippocampal axis from CA3 to subiculum implements entorhinal–hippocampal function (Henriksen et al, 2010; Bellistri et al, 2013; Schomburg et al, 2014; Laurent et al, 2015).…”

Differential effects of oxytocin on mouse hippocampal oscillations in vitro

“…in the theta frequency range), these slices expressed a nested gamma‐frequency oscillation at about 45 Hz (Fig. , Butler et al ., ; Akam et al ., ; Pastoll et al ., ). Similar to our previous findings with pharmacologically induced gamma oscillations, the properties of optogenetically induced gamma oscillations did not change in the presence of 100 n m TGOT [Fig.…”

“…Typical firing rates of FSI in their in vitro model were below 1 Hz during baseline conditions and reached 8 Hz in presence of TGOT. In vitro models of gamma‐frequency oscillations typically produce firing rates of FSI around 30–45 Hz (Bartos et al ., ; Butler et al ., ), and SPW‐R oscillations in vitro go along with firing rates around 6 Hz (Bähner et al ., ). Thus, OT can have a strong impact on firing frequency during SPW‐R oscillations while the high‐frequency firing of FSI during gamma activity may limit the range for additional enhancement.…”

Differential and complementary roles of medial and lateral septum in the orchestration of limbic oscillations and signal integration

“…The activity of septal fast‐spiking GABAergic neurons is also linked to the induction of high‐frequency gamma oscillations (30–100 Hz; Buzsaki & Wang, ). Both slow theta and fast gamma hippocampal oscillations depend on the burst discharges of septal interneurons, but hippocampal theta and gamma are also mediated by the activity of entorhinal inputs (Pernia‐Andrade & Jonas, ) and local rhythm generators (Goutagny et al ., ; Butler et al ., ). One hypothesis is that hippocampal self‐generated theta generators (Kocsis et al ., ; Goutagny et al ., ; Stark et al ., ) can resonate or interfere with the septum‐generated theta oscillation, which in turn could amplify or reduce the limbic theta waves (Patel et al ., ).…”