SLIT-2 conditional knock-out in parvalbumin-expressing interneurons lead to anxiety deficits

Abstract

Parvalbumin-expressing (PV) interneurons innervate a large amount of neighboring pyramidal neurons and establish perisomatic inhibition of pyramidal neurons. The lack of perisomatic inhibition is one of the factors for neurological dysfunction in seizures, autism spectrum disorders and schizophrenia (Baohan et al., 2016). PV neurons are found essential for learning and drives both long-term network plasticity and memory formation (Ognjanovski et al., 2017). And studies show that PV-Cre mutant mouse strain represents a model that may be useful in studies of neuronal plasticity (Hippenmeyer et al., 2005). Knowing that Slit-2 protein has been shown to be highly enriched in PV cells which promotes axon elongation and maturation (Paul et al., 2017). The lack of Slit-2 protein in PV neurons of PV-Cre mutant mice can potentially affect their maturation and proper functioning, and ultimately lead to memory defects and behavioral changes. We therefore aim at testing this hypothesis by performing behavioral tests on PV-Cre mutant mice in which Slit-2 protein is deleted from PV neurons to evaluate their memory processing and memory formation. We will also assess if this deletion affects PV axon elongation and overall morphology.