D-type potassium channels normalize action potential firing between dorsal and ventral CA1 neurons of the mouse hippocampus

Abstract

Specific memory processes and neurological disorders can be ascribed to different dorsoventral regions of the hippocampus. Recently, differences in the anatomical and physiological properties between dorsal and ventral hippocampal CA1 neurons were described for both the rat and mouse hippocampus and have greatly contributed to our understanding of these processes. While differences in the subthreshold properties were similar between rat and mouse neurons, differences in action potential output between dorsal and ventral neurons were strikingly less divergent in mouse compared with rat CA1 neurons. Here, we investigate the mechanism underlying the lack of difference in action potential firing between dorsal and ventral CA1 pyramidal neurons in mouse hippocampus. Consistent with rat, we found that ventral CA1 neurons had a more depolarized resting membrane potential and higher input resistance than dorsal CA1 neurons in the mouse hippocampus. Despite these differences, action potential output in response to current injection was not significantly different. We found that ventral neurons have a more depolarized action potential threshold compared with dorsal neurons and that threshold in ventral neurons was more sensitive to block of KV1 channels compared with dorsal neurons. Outside-out voltage-clamp recordings found that slowly inactivating K+ currents were larger in ventral CA1 neurons. These results suggest that, despite differences in subthreshold properties between dorsal and ventral CA1 neurons, action potential output is normalized by the differential functional expression of D-type K+ channels. NEW & NOTEWORTHY Understanding differences in neurons within a brain region is integral in the reliable interpretation of comparative studies. Our findings identify a novel mechanism by which D-type potassium channels normalize action potential firing between dorsal and ventral CA1 neurons of mouse hippocampus despite differences in subthreshold intrinsic properties. Action potential threshold in ventral neurons is influenced by a greater functional expression of D-type potassium channels resulting in a depolarized action potential threshold compared with dorsal hippocampus.

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

“…The properties of hippocampal pyramidal neurons vary along the dorsal ventral axis of the hippocampus (Dougherty et al 2012; Kim and Johnston 2015; Malik et al 2016; Ordemann et al 2019). More recently, OLM cells were shown to have distinct intrinsic physiological properties depending on the dorsal ventral location of the cell (Hilscher et al 2019).…”

Differential developmental refinement of the intrinsic electrophysiological properties of CA1 pyramidal neurons from the rat dorsal and ventral hippocampus

“…This suggests the presence of a complicating factor in VHC neurons that disrupts the correlation between V thr at −65 mV and the max dV/dt . Interestingly, Ordemann et al have recently described a D‐type potassium current that depolarizes V thr in VHC neurons of the adult mouse hippocampus, and future work will be necessary to determine if a similar mechanism depolarizes V thr in rat VHC neurons (Ordemann, Apgar, & Brager, ).…”

Fragile X Mental Retardation Protein modulates somatic D-type K+channels and action potential threshold in the mouse prefrontal cortex

“…The biophysical properties of D-type K + channels allow them to act as high pass filters by depolarizing the voltage threshold for action potential generation in response to slow, but not fast, voltage trajectories. It was previously shown that current injections of variable duration can be used to separate the contribution of IKD to action potential threshold (Higgs and Spain, 2011;Kalmbach et al, 2015;Ordemann et al, 2019). Given that FMRP increases IKD in L5 ET, we expect that expression of FMRP will depolarize ET neuron action potential threshold for longer current injections.…”

“…This allows for a broader time window during which D-type channels can influence changes in membrane potential. D-type K + channels are enriched in the axo-somatic region of neurons where they oppose depolarization and exert strong influence over the threshold for action potential generation (Kole et al, 2007;Higgs and Spain, 2011;Ordemann et al, 2019). Changes in K + channel function contribute to neuronal hyperexcitability in neurological disorders such as epilepsy and episodic ataxia (Jan and Jan, 2012;Noebels et al, 2012;D'Adamo et al, 2020b).…”