The translationally relevant mouse model of the 15q13.3 microdeletion syndrome reveals deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia

Research output: Contribution to journalArticle

Abstract

AIM: To date, the understanding and development of novel treatments for mental illness is hampered by inadequate animal models. For instance, it is unclear to what extent commonly used behavioural tests in animals can inform us on the mental and affective aspects of schizophrenia.

METHODS: To link pathophysiological processes in an animal model to clinical findings, we have here utilized the recently developed Df(h15q13)/+ mouse model for detailed investigations of cortical neuronal engagement during pre-attentive processing of auditory information from two back-translational auditory paradigms. We also investigate if compromised putative fast-spiking interneurone (FSI) function can be restored through pharmacological intervention using the Kv3.1 channel opener RE1. Chronic multi-array electrodes in primary auditory cortex were used to record single cell firing from putative pyramidal and FSI in awake animals during processing of auditory sensory information.

RESULTS: We find a decreased amplitude in the response to auditory stimuli and reduced recruitment of neurones to fast steady-state gamma oscillatory activity. These results resemble encephalography recordings in patients with schizophrenia. Furthermore, the probability of interneurones to fire with low interspike intervals during 80 Hz auditory stimulation was reduced in Df(h15q13)/+ mice, an effect that was partially reversed by the Kv3.1 channel modulator, RE1.

CONCLUSIONS: This study offers insight into the consequences on a neuronal level of carrying the 15q13.3 microdeletion. Furthermore, it points to deficient functioning of interneurones as a potential pathophysiological mechanism in schizophrenia and suggests a therapeutic potential of Kv3.1 channel openers.

Details

Authors
Organisations
External organisations
  • H. Lundbeck A/S
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
Original languageEnglish
Pages (from-to)124-136
JournalActa Physiologica
Volume220
Issue number1
Early online date2016 Jul 1
StatePublished - 2017 May
Peer-reviewedYes