Reduced K⁺ Channel Inactivation, Spike Broadening, and After-Hyperpolarization in Kvβ1.1-Deficient Mice with Impaired Learning

Abstract

A-type K+ channels are known to regulate neuronal firing, but their role in repetitive firing and learning in mammals is not well characterized. To determine the contribution of the auxiliary K+ channel subunit Kvβ1.1 to A-type K+ currents and to study the physiological role of A-type K+ channels in repetitive firing and learning, we deleted the Kvβ1.1 gene in mice. The loss of Kvβ1.1 resulted in a reduced K+ current inactivation in hippocampal CA1 pyramidal neurons. Furthermore, in the mutant neurons, frequency-dependent spike broadening and the slow afterhyperpolarization (sAHP) were reduced. This suggests that Kvβ1.1-dependent A-type K+ channels contribute to frequency-dependent spike broadening and may regulate the sAHP by controlling Ca2+ influx during action potentials. The Kvβ1.1-deficient mice showed normal synaptic plasticity but were impaired in the learning of a water maze test and in the social transmission of food preference task, indicating that the Kvβ1.1 subunit contributes to certain types of learning and memory.

Morpho-electric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex

“…Notably, spike adaptation properties showed a strong inverse relationship with sag across the dataset (Fig S2A). Sag is often mediated by HCN channels ( 31 ) and spike broadening by specific K+ channels ( 32, 33 ), so this finding may indicate a functional relationship between these channels in all subclasses of human L1 neurons.…”

“…Notably, spike adaptation properties showed a strong inverse relationship with sag across the dataset (Fig S2A). Sag is often mediated by HCN channels (31) and spike broadening by specific K+ channels (32,33), so this finding may indicate a functional relationship between these channels in all subclasses of human L1 neurons. LAMP5 cells, the largest subclass, corresponded to the classical neurogliaform cell type (34), with highly branched, descending dendrites and horizontally elongated axons, either with a rectangular or triangular shape.…”

Social transmission of food preference in mice: Methodology and application to galanin-overexpressing transgenic mice.

“…STFP is a test of olfactory memory that was developed in rats (Berger-Sweeney, Stearns, Frick, Beard, & Baxter, 2000; Bunsey & Eichenbaum, 1995; Galef & Wigmore, 1983; Strupp & Levitsky, 1984; Winocur, McDonald, & Moscovitch, 2001) and is becoming increasingly used in mice (Choleris, Guo, Liu, Mainardi, & Valsecchi, 1997; Ferguson, Anagnostaras, Silva, & Herschman, 2000; Gass et al, 1998; Giese et al, 1998; Kogan et al, 1996; Mayeux-Portas, File, Stewart, & Morris, 2000; Valsecchi & Galef, 1989). In the first phase (interaction phase) of this task, a demonstrator mouse is allowed to eat food mixed with a novel flavor and is then allowed to interact with conspecific observer mice.…”

A missense mutation in Kcnc3 causes hippocampal learning deficits in mice

“…Voltage-gated potassium channels play key roles in the electrical properties of neurons, and many of them are expressed in the hippocampus. However, only Kv4.2 (KCND2) and Kv12.2 (KCNH3) have been previously implicated in learning and memory ( 61 – 68 ).…”