Transient callosal projections of L4 neurons are eliminated for the acquisition of local connectivity

Abstract

Interhemispheric axons of the corpus callosum (CC) facilitate the higher order functions of the cerebral cortex. According to current views, callosal and non-callosal fates are determined early after a neuron’s birth, and certain populations, such as cortical layer (L) 4 excitatory neurons of the primary somatosensory (S1) barrel, project only ipsilaterally. Using a novel axonal-retrotracing strategy and GFP-targeted visualization of Rorb+ neurons, we instead demonstrate that L4 neurons develop transient interhemispheric axons. Locally restricted L4 connectivity emerges when exuberant contralateral axons are refined in an area- and layer-specific manner during postnatal development. Surgical and genetic interventions of sensory circuits demonstrate that refinement rates depend on distinct inputs from sensory-specific thalamic nuclei. Reductions in input-dependent refinement result in mature functional interhemispheric hyperconnectivity, demonstrating the plasticity and bona fide callosal potential of L4 neurons. Thus, L4 neurons discard alternative interhemispheric circuits as instructed by thalamic input. This may ensure optimal wiring.

Ontogeny of the VIP+ interneuron sensory-motor circuit prior to active whisking

“…We have used a viral optogenetic strategy, previously employed to delineate the emergence of prefrontal cortex-amygdala connectivity (Arruda-Carvalho et al, 2017), to show that long-range connections from anteriormotor areas engage not only with pyramidal cells in S1BF, but also VIP+ INs (Lee et al, 2013;Wall et al, 2016) as early as the CPP. This extends our knowledge of how brain-wide circuits come online (Arruda-Carvalho et al, 2017;De León Reyes et al, 2019) and identifies the recruitment of GABAergic interneurons during circuit plasticity and maturation across brain areas. The relative balance between longrange and local influences remains to be investigated but our data argues for an initial compartmentalization of these two influences prior to the potentiation of feedforward and local synapses in supragranular layers at the onset of active perception (Bureau et al, 2004;Clem and Barth, 2006;Clem et al, 2008;Itami and Kimura, 2012;Wen and Barth, 2011).…”

“…However to date developmental studies have largely focused on emergent connectivity within a given sensory area (e.g. Erzurumlu and Gaspar, 2012;Hensch, 2005) and, as a consequence, relatively little is known about how long range synaptic connections integrate with local circuits within the first few postnatal weeks (Arruda-Carvalho et al, 2017;De León Reyes et al, 2019). The need for such an understanding is evident in somatosensory barrel field (S1BF), a primary sensory neocortical area that requires processing of both motor -active exploration of the target by the vibrissaeand tactile sensory information arriving in S1BF (Petersen, 2019).…”

Circuits in the absence of cortical layers: increased callosal connectivity in reeler mice revealed by brain-wide input mapping of VIP neurons in barrel cortex

“…in (Innocenti and Price, 2005)). In the somatosensory system, CPNs invade the contralateral cortex by P5, reach their maximum density by P10 and then reduce again to reach a stable level of innervation by P20 (Fenlon et al, 2017; De Leon Reyes et al, 2019). Because the establishment of permanent callosal synapses is only finished in the third postnatal week, they might mature based on the network activity generated by already existing ipsilateral connections (Petreanu et al, 2007; Suárez et al, 2014).…”

New Molecular Players in the Development of Callosal Projections

“…Guidance of callosal axons is a series of well-orchestrated interactions of attractive and repulsive cues that navigates extending axons to their targets on the contralateral side [ 21 , 90 , 91 ]. Callosal axons from lower cortical layers cross the midline during the embryonic period, while callosal axons from upper cortical layers do not reach the midline until postnatal stages [ 92 ]. The guidance cues for early callosal axon growth are mainly provided by midline glia and pioneering axons [ 27 , 93 ], but other brain tissues, e.g., meninges, or CPNs themselves, also participate in delivering axon guiding cues [ 94 , 95 ].…”

“…Callosal axons from lower cortical layers cross the midline during the embryonic period, while callosal axons from upper cortical layers reach the midline during the postnatal stage [ 92 ]. Although the mechanisms underlying the axon guidance through the midline during prenatal period have been extensively studied [ 9 , 86 , 96 , 100 , 102 ], the mechanisms of postnatal callosal axon guidance remains to be addressed.…”