Local Optogenetic Induction of Fast (20–40 Hz) Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity

Abstract

The neurophysiological processes that can cause theta-to-gamma frequency range (4–80 Hz) network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2) expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20–40 Hz) field potential oscillations in hippocampal area CA1 in vitro (at 25°C) and in vivo (i.e., slightly anesthetized NEX-Cre-ChR2 mice). As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer) and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I) oscillations. Consistently, the oscillations comprised rhythmically occurring population spikes (generated by pyramidal cells) and their frequency increased with increasing spectral power. We further demonstrate that the optogenetically driven CA1 oscillations, which remain stable over repeated evocations, are impaired by the stress hormone corticotropin-releasing factor (CRF, 125 nM) in vitro and, even more remarkably, found that they are accompanied by concurrent states of enforced theta activity in the memory-associated perirhinal cortex (PrC) in vivo. The latter phenomenon most likely derives from neurotransmission via a known, but poorly studied excitatory CA1→PrC pathway. Collectively, our data provide evidence for the existence of a prototypic (CRF-sensitive) P-I gamma rhythm generator in area CA1 and suggest that CA1 P-I oscillations can rapidly up-regulate theta activity strength in hippocampus-innervated rhinal networks, at least in the PrC.

Chronic Paroxetine Treatment Prevents the Emergence of Abnormal Electroencephalogram Oscillations in Huntington's Disease Mice

“…Although the functional significance of abnormal high-frequency EEG oscillations in these neuropsychiatric disorders is unknown, gamma oscillations have attracted a lot of attention in recent years because of the role they play in feature binding [ 43 ], object representation [ 44 ], and selective attention [ 45 ]. Gamma oscillations are generated in the cortex and hippocampus [ 46 , 47 ]. Since basal ganglia is severely affected in HD, insufficient inhibition of cortical activity by cortical projecting neurons of basal ganglia could account, at least in part, for the abnormal low-gamma EEG oscillations seen in HD [ 10 ].…”

Comparison of three gamma oscillations in the mouse entorhinal–hippocampal system

“…A). This is consistent with previous studies of ChR2‐induced CA1 gamma oscillations (Dine et al ., ), where it was observed that blocking muscarinic acetylcholine receptors with atropine eliminated these residual gamma oscillations. These results indicate that a fast excitatory–inhibitory feedback loop underlies the generation of gamma oscillations during theta‐rhythmic activation of principal cells in all three regions, consistent with a PING mechanism of generation (Fisahn et al ., ; Whittington et al ., ).…”

Substance P and pain chronicity

“…In the cortex and other subcortical areas, PNNs preferentially surround GABAergic interneurons containing the calcium-binding protein parvalbumin. These specific cells have been recently identified as fast-spiking cells relevant for gamma-oscillations (Dine et al 2016 ).…”