Kv4.2 knockout mice display learning and memory deficits in the Lashley maze

Abstract

Background: Potassium channels have been shown to be involved in neural plasticity and learning. Kv4.2 is a subunit of the A-type potassium channel. Kv4.2 channels modulate excitability in the dendrites of pyramidal neurons in the cortex and hippocampus. Deletion of Kv4.2 results in spatial learning and conditioned fear deficits; however, previous studies have only examined deletion of Kv4.2 in aversive learning tests. Methods: For the current study, we used the Lashley maze as an appetitive learning test. We examined Kv4.2 wildtype (WT) and knockout (KO) mice in the Lashley maze over 4 days during adulthood. The first day consisted of habituating the mice to the maze. The mice then received five trials per day for the next 3 days. The number of errors and the time to the goal box was recorded for each trial. The goal box contained a weigh boat with an appetitive reward (gelatin with sugar). There was an intertrial interval of 15 minutes. Results: We found that Kv4.2 KO mice committed more errors across the trials compared to the WT mice p<0.001. There was no difference in the latency to find the goal box over the period. Discussion: Our finding that deletion of Kv4.2 resulted in more errors in the Lashley maze across 15 trials contribute to a growing body of evidence that Kv4.2 channels are significantly involved in learning and memory.

Keywords: A type current; Kv4.2; hippocampus; lashley maze; learning; potassium ion channel.

Figure 1.. Schematic overview of the Lashley maze. The correct path: ACFILN.

On day 1 the test mice were habituated to each of the chambers of the maze. For each mouse, a weigh boat containing a small amount of the gelatin was placed in the goal box (area N). The mice began habituation in section BCD with door 1 and door A blocked and were allowed to explore for 3 minutes. The mice were then moved to section GFE with doors 1 and 2 blocked, and again allowed to explore for 3 minutes. The same was then repeated in area HIJ for another 3 minutes. Finally the mice were moved to area MLK with door 3 and door N blocked and allowed to explore for 5 minutes. The apparatus was cleaned using 30% isopropanol between each mouse and a new weigh boat with fresh gelatin was used for each mouse. On day 2 a fresh weigh boat containing a small amount of gelatin was placed in the area N and the test mouse was placed in area A. The amount of time and path used to reach the goal box was recorded. The number of repeated sections the mouse entered on the way to the goal were recorded. If the mouse did not reach the end after 5 minutes it was guided to the goal using a piece of acrylic plastic used to block the doors, to prevent back tracking and wrong turns. Each mouse received 5 trials, one every 15 minutes. The same procedures were then repeated on days 3 and 4 for a total of 15 trials per mouse.

Figure 2.. Number of errors and time to completion for maze.

There was a significant difference between genotypes with the WT mice committing fewer errors when compared to the KO mice. There was no difference in the time to completion of Lashley maze for the WT and KO mice. A. The graph reflects the number of errors committed by the WT and KO mice across the 15 trials. B. The graph shows the time to completion of the Lashley maze across the 15 trials between the WT and KO mice. There was a group × time interaction across the 15 trials. An independent t-test revealed a significant difference on the first trial. No other differences were found in the remaining 14 trials. WT n = 11, KO n = 9. * = p < 0.05; *** = p < 0.001.