Molecularly Defined Subplate Neurons Project Both to Thalamocortical Recipient Layers and Thalamus

Abstract

In mammals, subplate neurons (SPNs) are among the first generated cortical neurons. While most SPNs exist only transiently during development, a number of SPNs persist among adult Layer 6b (L6b). During development, SPNs receive thalamic and intra-cortical input, and primarily project to Layer 4 (L4). SPNs are critical for the anatomical and functional development of thalamocortical connections and also pioneer corticothalamic projections. Since SPNs are heterogeneous, SPN subpopulations might serve different roles. Here, we investigate the connectivity of one subpopulation, complexin-3 (Cplx3)-positive SPNs (Cplx3-SPNs), in mouse whisker somatosensory (barrel) cortex (S1). We find that many Cplx3-SPNs survive into adulthood and become a subpopulation of L6b. Cplx3-SPNs axons project to thalamorecipient layers, that is, L4, 5a, and 1. The L4 projections are biased towards the septal regions between barrels in the second postnatal week. Thus, S1 Cplx3-SPN targets co-localize with the eventual projections of the medial posterior thalamic nucleus (POm). In addition to their cortical targets, Cplx3-SPNs also extend long-range axons to several thalamic nuclei, including POm. Thus, Cplx3-SPN/L6b neurons are associated with paralemniscal pathways and can potentially directly link thalamocortical and corticothalamic circuits. This suggests an additional key role for SPNs in the establishment and maintenance of thalamocortical processing.

Laminar specific gene expression reveals differences in postnatal laminar maturation in mouse auditory, visual, and somatosensory cortex

“…The vesicular glutamate transporter 2 (vGlut2) antibody was raised against purified recombinant protein containing amino acids 510–582 of rat vGlut2 and recognized a single band of ∼65 kDa with Western blot on synaptic vesicle fraction of rat brain (manufacturer's technical information). An immunostaining pattern in layer 4 had been reported in mouse somatosensory and motor cortexes (Matsui et al, ; Tantirigama, Oswald, Duynstee, Hughes, & Empson, ; Viswanathan, Sheikh, Looger, & Kanold, ).…”

Distinct Translaminar Glutamatergic Circuits to GABAergic Interneurons in the Neonatal Auditory Cortex

“…Subplate neurons are important because they are the first cortical neurons to receive thalamic inputs and because they relay these inputs into the developing cortical plate before thalamocortical inputs mature (Kanold and Luhmann, 2010; Viswanathan et al, 2016; Zhao et al, 2009). Subplate neurons are required for the maturation of thalamocortical connections (Kanold et al, 2003), cortical network activity (Dupont et al, 2006; Kanold et al, 2003; Kanold and Luhmann, 2010; Tolner et al, 2012), and for the maturation of inhibitory transmission (Kanold and Shatz, 2006).…”

“…While hippocampal interneurons have silent synapses at young ages (Matta et al, 2013; Riebe et al, 2009) the presence of silent synapses on cortical interneurons as well as the presynaptic laminar source of such synapses is unknown. Thalamic activity can reach cortical interneurons via multiple potential intra-cortical pathways such as subplate neurons, which relay thalamic input to L4 before the maturation of thalamocortical connections (Barkat et al, 2011; Kanold and Luhmann, 2010; Viswanathan et al, 2016; Zhao et al, 2009). We thus investigated the intra-cortical sources of excitatory input to developing cortical GABAergic interneurons and delineated which spatial circuits were NMDAR-only and thus might precede later mature connections.…”

Understanding neural circuit development through theory and models

“…The depolarizing action of GABA in immature circuits (reviewed in [32,33]) is an example of a transient developmental feature which several models have utilized for the propagation of spontaneous activity [30, 31 • ] -this feature seems to be important to support spontaneous activity in networks where immature neurons have high excitability thresholds, and weak and unreliable connectivity. The subplate is a transient structure with relatively mature properties, which serves as a scaffold to establish strong and precise connectivity between the thalamus and cortex and then disappears [34,35]. As a third example, we mention the transient excitatory feedback connectivity between the thalamic reticular nucleus (TRN), thalamus and visual cortex, which appears necessary for the generation of feedforward connectivity along the developing visual pathway [36 •• ].…”