Presentation Date: Feb 14, 2026
AGSA Abstract
Higher forebrain operations are mediated through an extensive network of corticothalamic, thalamocortical and corticocortical connections. Within the corticothalamic network, two projection systems have been classically regarded to have complementary roles; the layer 5 corticothalamic pathways are considered ‘drivers’ of thalamic activity, while the layer 6a pathways are considered ‘modulators’ of thalamic activity. Recently through, a third corticothalamic pathway, originating from layer 6b, has received increased attention, in part due to its laminar role in mediating forebrain wake states. Moreover, we have shown that this sublayer may be a significant source of contralateral corticothalamic projections originating from limbic/prefrontal cortical areas. As such, layer 6b is uniquely poised to influence contralateral forebrain operations via overlooked ipsicortico-contrathalamocortical loops. Thus, to assess the organization of this circuit, we characterized the corticothalamic projections from cortical layer 6b of three cortical areas: primary auditory cortex (A1), insular cortex (IC), and prefrontal cortex (PFC). We employed the Drd1a-Cre mouse lines, which specifically expresses Cre-recombinase in layer 6b corticothalamic neurons. We stereotaxically injected floxed anterograde adeno-associated virus expressing various fluorophores, EYFP (green) and mCherry (red), and examined the terminations of ipsilateral and contralateral corticothalamic projections to specific thalamic nuclei. These projections differ according to the area injected, topographic segregation of terminal fields, characteristic morphological features, with no contralateral projections observed from A1. Our experiments addressed overlooked neuronal pathways involved in forebrain processing, which could offer insights into deficits in neurological disorders mediated by these pathways.
