Heterogeneity in Kv2 Channel Expression Shapes Action Potential Characteristics and Firing Patterns in CA1 versus CA2 Hippocampal Pyramidal Neurons

Abstract

The CA1 region of the hippocampus plays a critical role in spatial and contextual memory, and has well-established circuitry, function and plasticity. In contrast, the properties of the flanking CA2 pyramidal neurons, important for social memory, and lacking CA1-like plasticity, remain relatively understudied. In particular, little is known regarding the expression of voltage-gated ion channels and the contribution of these channels to the distinct properties of intrinsic excitability, action potential waveform, firing patterns and neurotransmission between CA1 and CA2 pyramidal neurons. In the present study, we used multiplex fluorescence immunolabeling of mouse brain sections, and whole-cell recordings in acute mouse brain slices, to define the role of heterogeneous expression of Kv2 family voltage-gated potassium channels in CA1 versus CA2 pyramidal cell excitability. Our results show that the somatodendritic delayed rectifier voltage-gated potassium (Kv) channel subunits Kv2.1, Kv2.2 and their auxiliary subunit AMIGO-1 have region-specific differences in expression in pyramidal neurons, with the highest expression levels in CA1, a sharp decrease at the CA1-CA2 boundary, and significantly reduced levels in CA2 neurons. Pyramidal neurons in CA1 exhibit a robust contribution of Guangxitoxin-1E-sensitive Kv2-based delayed rectifier current to action potential shape and after-hyperpolarization potential relative to that seen in CA2 pyramidal neurons. Our results indicate that robust Kv2 channel expression confers a distinct pattern of intrinsic excitability to CA1 pyramidal neurons, potentially contributing to their different roles in hippocampal network function.

Significance Statement CA1 and CA2 pyramidal neurons (PNs) play distinct roles in hippocampal network function. Determining the molecular mechanisms that regulate excitability of CA1 versus CA2 PNs is important in understanding their distinct plasticity, and their different roles in spatial and contextual versus social memory, respectively. Here we show that specific characteristics of action potential firing properties in CA1 versus CA2 PNs can be attributed to Kv2 channels, with higher expression levels and functional contributions in CA1 versus CA2. Our results suggest that Kv2 channel expression is an important determinant of specific aspects of action potential firing properties in CA1 versus CA2 PNs, and that regulation of membrane excitability by Kv2 channels may contribute to the robust synaptic plasticity of CA1 PNs.