Dorsoventral differences in Kv7/M‐current and its impact on resonance, temporal summation and excitability in rat hippocampal pyramidal cells

Abstract

Key pointsr Kv7 (KCNQ/M) channels are known to control excitability and generate subthreshold M-resonance in CA1 hippocampal pyramidal cells, but their properties and functions have not previously been compared along the dorsoventral (septotemporal) axis r We used whole-cell recordings to compare electrophysiological properties of dorsal and ventral CA1 pyramidal cells in hippocampal slices from 3-to 4-week-old rats r Blockade of Kv7/M-channels with 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride (XE991) had a stronger impact on electrical properties in dorsal than ventral pyramidal cells, including input resistance, temporal summation, M-resonance, spike threshold, medium after-hyperpolarization, excitability, and spike frequency adaptation. r I M -dependent differences in excitability and resonance may be important for rate and phase coding of CA1 place cells along the dorsoventral axis and may enhance epileptiform activity in ventral pyramidal cells.Abstract In rodent hippocampi, the connections, gene expression and functions differ along the dorsoventral (D-V) axis. CA1 pyramidal cells show increasing excitability along the D-V axis, although the underlying mechanism is not known. In the present study, we investigated how the M-current (I M ), caused by Kv7/M (KCNQ) potassium channels, and known to often control neuronal excitability, contributes to D-V differences in intrinsic properties of CA1 pyramidal cells. Using whole-cell patch clamp recordings and the selective Kv7/M blocker 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride (XE991) in hippocampal slices from 3-to 4-week-old rats, we found that: (i) I M had a stronger impact on subthreshold electrical properties in dorsal than ventral CA1 pyramidal cells, including input resistance, temporal summation of artificial synaptic potentials, and M-resonance; (ii) I M activated at more negative potentials (left-shifted) and had larger peak amplitude in the dorsal than ventral CA1; and (iii) the initial spike threshold (during ramp depolarizations) was elevated, and the medium after-hyperpolarization and spike frequency adaptation were increased (i.e. excitability was lower) in the dorsal rather than ventral CA1. These differences were abolished or reduced by application of XE991, indicating that they were caused by I M . Thus, it appears that I M has stronger effects in dorsal than in ventral rat CA1 pyramidal cells because of a larger maximal M-conductance and left-shifted activation curve in the dorsal cells. These mechanisms may contribute to D-V Authors C. Hönigsperger and M. Marosi contributed equally to this work.

Switching between persistent firing and depolarization block in individual rat CA1 pyramidal neurons

“…However, too few dorsal neurons were sampled to allow statistical evaluation of this distribution (χ 2 test). Our findings are tentative but in line with data suggesting stronger epileptiform activity in ventral regions of CA1 (Hönigsperger, Marosi, Murphy, & Storm, ).…”

Electrophysiological Properties of CA1 Pyramidal Neurons along the Longitudinal Axis of the Mouse Hippocampus

“…Indeed, in rats, membrane conductances near rest differ from DH to VH (i.e. Kv723, HNCN24 and GIRK25) and dendritic surface area of DH neurons is larger than that of VH ones101126. We did not observe any significant difference in the average membrane capacitance between VH and DH cells but we measured a similar specific conductance, suggesting that differences in RMP and Rin might depend on both cell dimension and ionic conductances.…”

Increased Persistent Sodium Current Causes Neuronal Hyperexcitability in the Entorhinal Cortex of Fmr1 Knockout Mice

“…There are 3 major types of sub-threshold currents in central neurons: M current (I M , carried by Kv7 channels), H current (I h , carried by HCN channels) and I NaP (Honigsperger et al, 2015; Stafstrom, 2007; Yamada-Hanff and Bean, 2013, 2015). We thus used specific inhibitors of I M , I h or I NaP to probe their role in regulating neuronal excitability in EC Layer III PCs.…”

“…Among the conductances that modulate neuronal excitability, the sub-threshold voltage-dependent conductances are critical to both the membrane excitability state and synaptic integration via regulation of both RMP and AP threshold. I M , I h and I NaP are the three major sub-threshold conductances in central neurons that are active and do not inactivate at sub-threshold voltages, and thus play a critical role in setting neuronal excitability (Honigsperger et al, 2015; Yamada-Hanff and Bean, 2013, 2015). However, these three conductances have distinct pattern of voltage dependence: subthreshold depolarization enhances I M and I NaP , but dampens I h ; in contrast, sub-threshold hyperpolarization dampens I M and I NaP , but enhances I h .…”