The effects of DISC1 disruption on the prefrontal cortex

Dysfunction of the prefrontal cortex is involved in schizophrenia and other psychiatric disorders. Therefore understanding the circuitry of the prefrontal cortex and how it is affected in psychiatric conditions is vital. One of the properties affected in psychiatric disorders is synaptic plasticity using a transgenic mouse with inducible disruption of DISC1 signalling. We have revealed a critical period for the establishment of mature properties, including synaptic plasticity. This coincides with a dynamic period of dendritic growth and spinogenesis. We want to establish whether there is a similar critical period in the prefrontal cortex.

Preliminary data suggest that a P7 DISC1 disruption has an effect on prefrontal cortex plasticity. Once this critical period is established in more detail we would like to examine effects of DISC1 disruption on the cellular properties and the cortical circuitry using imaging techniques. We have used RNAseq to identify downstream targets of P7 DISC1 disruption in barrel cortex and are keen to repeat this in the prefrontal cortex and attempt to rescue synaptic plasticity by agonising target molecules.

Our results will provide insight into the role of DISC1 in the prefrontal cortex and form a basis for subsequent studies