P.1.c.020 - Cadherin-13, a risk factor for neurodevelopmental disorders, modulates serotonin system development via radial glia interaction

Abstract

The dorsal periaqueductal grey matter (dPAG) and the deep layers of the superior colliculus (dlSC) have been implicated in the organisation of innate fear-related defensive behaviours. Furthermore, GABAergic neurons from the substantia nigra pars reticulata (SNpr) connected to the dlSC and dPAG receive convergent disinhibitory inputs from the caudate-putamen (CPu), comprising the neostriatum, and modulate defence responses elicited by midbrain tectum stimulation. The purpose of this work was to study the effect of either excitatory cortico-neostriatal input blockade or neostriato-nigral GABAergic disinhibitory output activation on the responsivity of GABAergic nigro-collicular tonic inhibitory pathways during the elicitation of panic attack-like defensive responses produced by bicuculline administration into the dlSC. Thus, we investigated the effects of microinjection of either the synaptic activity blocker cobalt chloride (CoCl2) or the NMDA receptor agonist N-methyl-D-aspartic acid in the CPu on the elaboration of the defensive behaviour elicited by the selective blockade of GABAA receptors in the dlSC. Our findings showed that pretreatment of the neostriatum with CoCl2 caused clear anxiolytic and panicolytic-like effects, reducing the incidence and duration of alertness and diminishing defensive immobility and explosive escape responses. On the other hand, pretreatment of the neostriatum with NMDA (40 nmol) caused a pro-aversive effect, enhancing running and jumping responses elicited by GABAergic disinhibition in the dlSC. We conclude from the data that the neostriato-nigral disinhibitory and nigro-collicular inhibitory GABAergic pathways modulate innate fear and panic attack-like responses organised by dlSC neurons.