Increased Callosal Connectivity in Reeler Mice Revealed by Brain-Wide Input Mapping of VIP Neurons in Barrel Cortex

Abstract

The neocortex is composed of layers. Whether layers constitute an essential framework for the formation of functional circuits is not well understood. We investigated the brain-wide input connectivity of vasoactive intestinal polypeptide (VIP) expressing neurons in the reeler mouse. This mutant is characterized by a migration deficit of cortical neurons so that no layers are formed. Still, neurons retain their properties and reeler mice show little cognitive impairment. We focused on VIP neurons because they are known to receive strong long-range inputs and have a typical laminar bias toward upper layers. In reeler, these neurons are more dispersed across the cortex. We mapped the brain-wide inputs of VIP neurons in barrel cortex of wild-type and reeler mice with rabies virus tracing. Innervation by subcortical inputs was not altered in reeler, in contrast to the cortical circuitry. Numbers of long-range ipsilateral cortical inputs were reduced in reeler, while contralateral inputs were strongly increased. Reeler mice had more callosal projection neurons. Hence, the corpus callosum was larger in reeler as shown by structural imaging. We argue that, in the absence of cortical layers, circuits with subcortical structures are maintained but cortical neurons establish a different network that largely preserves cognitive functions.

VIP-Expressing GABAergic Neurons: Disinhibitory vs. Inhibitory Motif and Its Role in Communication Across Neocortical Areas

“…In a complementary condition, the S1 VIP-expressing neurons lost their preferential abundance in the superficial layers. Moreover, the long-range inputs onto VIP-expressing neurons from ipsilateral and contralateral cortices were compromised, contributing to a dysfunctional elaboration of the incoming inputs ( Hafner et al, 2021 ). In addition, Goff and Goldberg (2019) have shown that the neocortical VIP-expressing neurons in Scn1a +/– mice, a mouse model of Dravet syndrome, exhibited impaired excitability.…”

The Reelin Receptor ApoER2 is a Cargo for the Adaptor Protein Complex AP-4: Implications for Hereditary Spastic Paraplegia

“…This neuronal subtype readily populates the corpus callosum, playing an essential role in interhemispheric connection (Pesold, Impagnatiello et al 1998). This process has been recently associated with Reelin signaling (Hafner, Guy et al 2021),suggesting that local Reelin secretion could participate in the maintenance of axonal tracks in the corpus callosum.…”