High and low expression of the hyperpolarization activated current (Ih) in mouse CA1 stratum oriens interneurons

Abstract

AbstractInhibitory interneurons are among the most diverse cell types in the brain; the hippocampus itself contains more than 28 different inhibitory interneurons. Interneurons are typically classified using a combination of physiological, morphological and biochemical observations. One broad separator is action potential firing: low threshold, regular spiking vs. higher threshold, fast spiking. We found that spike frequency adaptation (SFA) was highly heterogeneous in low threshold interneurons in the mouse stratum oriens region of area CA1. Analysis with a k-means clustering algorithm parsed the data set into two distinct clusters based on a constellation of physiological parameters and reliably sorted strong and weak SFA cells into different groups. Interneurons with strong SFA fired fewer action potentials across a range of current inputs and had lower input resistance compared to cells with weak SFA. Strong SFA cells also had higher sag and rebound in response to hyperpolarizing current injections. Morphological analysis shows no difference between the two cell types and the cell types did not segregate along the dorsal-ventral axis of the hippocampus. Strong and weak SFA cells were labeled in hippocampal slices from SST:cre Ai14 mice suggesting both cells express somatostatin. Voltage-clamp recordings showed hyperpolarization activated current Ih was significantly larger in strong SFA cells compared to weak SFA cells. We suggest that the strong SFA cell represents a previously uncharacterized type of CA1 stratum oriens interneuron. Due to the combination of physiological parameters of these cells, we will refer to them as Low Threshold High Ih (LTH) cells.Key PointsSpike frequency adaptation (SFA) was highly variable among stratum oriens interneuronsAdapting stratum oriens interneurons were separated into two cell groups using multiple subthreshold and action potential parameters by cluster analysisCells with strong SFA fired fewer action potentials for a given current injection, had lower input resistance and more sag and rebound compared to weak SFA cellsThe physiological differences were not correlated with neuron morphology, location in stratum oriens, or anatomical location along the dorsal-ventral axis of the hippocampusVoltage-clamp recordings revealed that strong SFA cells had higher density of the hyperpolarization activated current Ih compared to weak SFA cells