Key pointsr The synchronisation of neuronal activity at gamma frequencies (30-100 Hz) could determine the effectiveness of neuronal communication.r Gamma oscillations in the CA1 region of the hippocampus in vitro was thought to be dependent on gamma oscillations generated in area CA3, but in vivo CA1 can generate gamma oscillations independently.r In this study we found that activating acetylcholine receptors induced stable gamma oscillations in the CA1 local network isolated in slices in vitro that were faster than those in CA3, but relied on similar neuronal circuitry involving feedback inhibition.r Gamma frequency inputs from CA3 (spontaneous in intact hippocampal slices or stimulated in isolated CA1) can suppress the local fast gamma oscillation in CA1 and force it to adopt the slower CA3 oscillation through feed-forward inhibition.r This modulation could allow CA1 to alternate between effective communication with the entorhinal cortex and CA3, which may regulate memory encoding and memory recall phases.Abstract Hippocampal gamma oscillations have been associated with cognitive functions including navigation and memory encoding/retrieval. Gamma oscillations in area CA1 are thought to depend on the oscillatory drive from CA3 (slow gamma) or the entorhinal cortex (fast gamma). Here we show that the local CA1 network can generate its own fast gamma that can be suppressed by slow gamma-paced inputs from CA3. Moderate acetylcholine receptor activation induces fast (45 ± 1 Hz) gamma in rat CA1 minislices and slow (33 ± 1 Hz) gamma in CA3 minislices in vitro. Using pharmacological tools, current-source density analysis and intracellular recordings from pyramidal cells and fast-spiking stratum pyramidale interneurons, we demonstrate that fast gamma in CA1 is of the pyramidal-interneuron network gamma (PING) type, with the firing of principal cells paced by recurrent perisomal IPSCs. The oscillation frequency was only weakly dependent on IPSC amplitude, and decreased to that of CA3 slow gamma by reducing IPSC decay rate or reducing interneuron activation through tonic inhibition of interneurons. Fast gamma in CA1 was replaced by slow CA3-driven gamma in unlesioned slices, which could be mimicked in CA1 minislices by sub-threshold 35 Hz Schaffer collateral stimulation that activated fast-spiking interneurons but hyperpolarised pyramidal cells, suggesting that slow gamma frequency CA3 outputs can suppress the CA1 fast gamma-generating network by feed-forward inhibition and replaces it with a slower gamma oscillation driven by feed-forward inhibition. The transition between the two gamma oscillation modes in CA1 might allow it to alternate between effective communication with the medial entorhinal cortex and CA3, which have different roles in encoding and recall of memory.

Oriens-lacunosum moleculare (OLM) cells are hippocampal inhibitory interneurons that are implicated in the regulation of information flow in the CA1 circuit, inhibiting cortical inputs to distal pyramidal cell dendrites, whilst disinhibiting CA3 inputs to pyramidal cells. OLM cells express metabotropic cholinergic (mAChR) and glutamatergic (mGluR) receptors, so modulation of these cells via these receptors may contribute to switching between functional modes of the hippocampus. Using a transgenic mouse line to identify OLM cells, we found that both mAChR and mGluR activation caused the cells to exhibit long-lasting depolarizing plateau potentials following evoked spike trains. Both mAChR- and mGluR-induced plateau potentials were eliminated by blocking transient receptor potential (TRP) channels, and were dependent on intracellular calcium concentration and calcium entry. Pharmacological tests indicated that Group I mGluRs are responsible for the glutamatergic induction of plateaus. There was also a pronounced synergy between the cholinergic and glutamatergic modulation, plateau potentials being generated by agonists applied together at concentrations too low to elicit any change when applied individually. This synergy could enable OLM cells to function as coincidence detectors of different neuromodulatory systems, leading to their enhanced and prolonged activation and a functional change in information flow within the hippocampus.

Oriens-lacunosum moleculare (OLM) cells are hippocampal inhibitory interneurons that have been implicated in regulation of information flow and synaptic plasticity in the CA1 circuit.Since anatomical evidence indicates that OLM cells express metabotopic cholinergic (mAChR) and glutamatergic (mGluR) receptors, such modulation of these cells may contribute to switching between functional modes of the hippocampus.Using a transgenic mouse line to identify the Chrna2-positive OLM cells, we investigated metabotropic neuromodulation of intrinsic properties of OLM cells.We found that both mAChR and mGluR activation increased the spontaneous action potential rate and caused the cells to exhibit long-lasting depolarizing plateau potentials following evoked spike trains.Both the mAChR-and mGluR-induced increased spontaneous firing rate and plateau potentials were dependent on intracellular calcium, and were eliminated by blocking Ca 2+ -dependent transient receptor potential (TRP) cation channels. At the receptor level, Group I mGluRs were found to be responsible for the glutamatergic modulation of the plateau potentials. There was also a pronounced synergy between the cholinergic and glutamatergic modulation of the plateau potentials.Our findings provide insights into how OLM cells are modulated by different neurotransmitters, and are likely to have functional implications on how OLM cells regulate hippocampal information processing during different brain states.