The T-type calcium channel antagonist Z944 rescues impairments in crossmodal and visual recognition memory in Genetic Absence Epilepsy Rats from Strasbourg

Neurobiol Dis. 2016 Oct;94:106-15. doi: 10.1016/j.nbd.2016.06.001. Epub 2016 Jun 6.

Abstract

Childhood absence epilepsy (CAE) is often comorbid with behavioral and cognitive symptoms, including impaired visual memory. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is an animal model closely resembling CAE; however, cognition in GAERS is poorly understood. Crossmodal object recognition (CMOR) is a recently developed memory task that examines not only purely visual and tactile memory, but also requires rodents to integrate sensory information about objects gained from tactile exploration to enable visual recognition. Both the visual and crossmodal variations of the CMOR task rely on the perirhinal cortex, an area with dense expression of T-type calcium channels. GAERS express a gain-in-function missense mutation in the Cav3.2 T-type calcium channel gene. Therefore, we tested whether the T-type calcium channel blocker Z944 dose dependently (1, 3, 10mg/kg; i.p.) altered CMOR memory in GAERS compared to the non-epileptic control (NEC) strain. GAERS demonstrated recognition memory deficits in the visual and crossmodal variations of the CMOR task that were reversed by the highest dose of Z944. Electroencephalogram recordings determined that deficits in CMOR memory in GAERS were not the result of seizures during task performance. In contrast, NEC showed a decrease in CMOR memory following Z944 treatment. These findings suggest that T-type calcium channels mediate CMOR in both the GAERS and NEC strains. Future research into the therapeutic potential of T-type calcium channel regulation may be particularly fruitful for the treatment of CAE and other disorders characterized by visual memory deficits.

Keywords: Absence epilepsy; Electroencephalography; GAERS; Object recognition; Perirhinal cortex.

MeSH terms

  • Acetamides / pharmacology*
  • Animals
  • Benzamides / pharmacology*
  • Calcium Channels, T-Type / drug effects*
  • Disease Models, Animal
  • Electroencephalography / methods
  • Epilepsy, Absence* / drug therapy
  • Epilepsy, Absence* / genetics
  • Female
  • Male
  • Memory / drug effects*
  • Memory Disorders* / drug therapy
  • Piperidines
  • Touch / physiology

Substances

  • Acetamides
  • Benzamides
  • Calcium Channels, T-Type
  • Piperidines
  • Z944