alexander kim neur 500 thesis final

IKCaInvolvement in the slow after-hyperpolarization in CA1

pyramidal cells and implications for spatial memory

Alexander B. KimSupervisor: Dr. Ray W. Turner

After-hyperpolarizations (AHPs)

Fast AHPVoltage-dependentCa2+-dependentLasts for 1-2 msBK channels

Medium AHPCa2+-dependentLasts for 50-100 msSK channels

Slow AHPOutward K+ currentCa2+-dependentLasts for secondsUnderlies spike accommodationUnknown channel(s)

IKCa is a candidate for the channel underlying the slow AHP in CA1 pyramidal cells

Spatial memory and the slow AHP

• Morris watermaze training reduces the slow AHP in CA1 pyramidal cells

• The slow AHP increases with age and correlates with spatial learning ability

• Application of a slow AHP blocker before retrieval impairs performance

Is modulation of IKCa responsible for the effects of learning on the slow AHP?

My Project

Hypothesis: The effects of learning on the slow AHP in CA1 pyramidal cells are mediated by modulation of IKCa.

Aim 1: Characterize the slow AHP in CA1 pyramidal cells of IKCa-/- mice

Aim 2: Evaluate spatial memory in IKCa-/- mice

Aim 3: Investigate the effects of spatial learning on the slow AHP in IKCa-/- mice

Generating a synaptically evoked slow AHP

IKCa-/- mice have a diminished slow AHP that is TRAM-34 insensitive

Water task training

Probe one day after training

Probe seven days after training

The effect of training on the slow AHP

Findings

• Deletion of IKCa diminishes the slow AHP in CA1 pyramidal cells.

• Deletion of IKCa alters spatial memory in the Morris water task.

Hypothesis: The effects of learning on the slow AHP in CA1 pyramidal cells are mediated by modulation of IKCa.

In progress…

AcknowledgementsBrian King

Bonita Gunning

Tom Seredynski

Simon Spanswick

Ray W. Turner

Cam Teskey

Ted Bartoletti

Hadhi Asmara

Colin Heath VI

Arsalan Rizwan

Steven Dykstra

Mirna Kruskic