Interneuronal Tuning Of Hippocampal CA1 Ripple Oscillations

High-frequency ripple oscillations(100-250 Hz)of local field potentials(LFPs),observed most prominently in the hippocampus during slow wave sleep or awake immobility,always accompanied by sharp wave(sharp wave-ripple complex),are associated with memory consolidation.We recorded LFPs as well as activities of ripple-related interneurons from mouse hippocampal CA1 area using multi-channel in vivo recording technique.These interneurons tend to fire at ripple troughs and can be assigned into two categories based on their firing profiles.Type ? ripple-related interneurons fire one action potential,while type ? interneurons fire doublets during each ripple cycle.We recorded a total of 35 type ? interneurons as well as 13 type? interneurons from 27 mice.To further study the relationship between interneuronal firing and ripple oscillations,we applied Granger Causality analysis.High Granger causality was observed with neuronal firing to local field potential within ripple frequency range.Therefore we assume that these interneurons play an essential role in tuning hippocampal ripple oscillations.Morphological studies have demonstrated multiple interneuron types in hippocampal CA1 area.We combined optogenetics with multi-channel in vivo recording technique,trying to identify ripple-related interneurons.In vivo recordings were made from optogenetically modified mouse with Parvalbumin-positive interneurons expressing excitatory channelrhodopsin ChR2.No evoked spikes were observed from 7 putative type ? ripple-related interneurons,while in 2 out of 3 interneurons with light evoked responses that we consider them type ? ripple-related interneurons based on their firing profiles.These results indicate that type ? ripple-related interneurons are not PV positive interneurons while type ? ripple-related interneurons might be.Hippocampal LFP represents the summation of postsynaptic potential of local pyramidal neuron assemblies.Hence we combined multi-channel in vivo recording with patch clamp recording technique,trying to reveal the relationship among ripple-related interneuronal firing,membrane potential fluctuation of pyramidal neuron and ripple oscillations of LFP.We observed ripple oscillations from membrane potential fluctuations of pyramidal neuron,which are superimposed on large amplitude depolarizing postsynaptic potential and highly synchronized with LFP ripple oscillations as well as ripple-related interneuronal firing.