Bottom-up inputs are required for the establishment of top-down connectivity onto cortical layer 1 neurogliaform cells

Abstract

Higher order feedback projections to sensory cortical areas converge on layer 1 (L1), the primary site for integration of top-down information via the apical dendrites of pyramidal neurons and L1 GABAergic interneurons. Here, we investigated the contribution of early thalamic inputs onto L1 interneurons for the establishment of top-down inputs in the primary visual cortex. We find that bottom-up thalamic inputs predominate during early L1 development and preferentially target neurogliaform cells. We find that these projections are critical for the subsequent strengthening of feedback inputs from the anterior cingulate cortex. Enucleation or selective removal of thalamic afferents blocked this phenomenon. Notably, while early activation of anterior cingulate afferents resulted in a premature strengthening of these top-down inputs to neurogliaform cells, this was also dependent on thalamic inputs. Our results demonstrate that the proper establishment of top-down feedback inputs critically depends on bottom-up inputs from the thalamus during early postnatal development.

Morpho-electric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex

“…The accompanying increase in soma density in human L1 could enable the conservation of the ‘blanket’ inhibitory function while also permitting some increased spatial/topographic selectivity. Neurogliaform circuit connectivity has been shown to be both tightly controlled ( 52, 53 ) and to exert strong effects on pyramidal cell sensory processing ( 1, 6 ). Neurogliaform cell density changes are thus likely to have either a direct or a compensatory function, perhaps linked to broader changes in excitatory to inhibitory cell ratios between mouse and human ( 21, 22, 54 ).…”

“…The copyright holder for this preprint this version posted October 25, 2022. ; https://doi.org/10.1101/2022.10.24.511199 doi: bioRxiv preprint has been shown to be both tightly controlled (52,53) and to exert strong effects on pyramidal cell sensory processing (1, 6). Neurogliaform cell density changes are thus likely to have either a direct or a compensatory function, perhaps linked to broader changes in excitatory to inhibitory cell ratios between mouse and human (21,22,54).…”

Id2 GABAergic interneurons: a neglected fourth major group of cortical inhibitory cells

“…The genetic strategies described here have also facilitated the in vivo recording of NGFCs. Outside of L1, where NGFCs express NDNF, a gene that has been used to facilitate the identification and in vivo recording of these neurons (84)(85)(86), recording of NGFCs has been limited to blind recordings followed by post-hoc identification (87-89), a very low yield approach. Here, we combined optogenetic labeling via Id2 intersectional genetics with silicon probe recordings to identify putative NGFCs in vivo (Fig.…”

Extrinsic control of the early postnatal CA1 hippocampal circuits

“…Such bottom-up thalamic drive is integrated within intracortical circuits capable of self-organizing their activity into network bursts, thus producing co-existing network patterns. Interestingly, these thalamic inputs transiently contact local interneurons in the neocortex, the same way VMT inputs are relayed by CA1 slm interneurons (Ibrahim et al, 2021; Marques-Smith et al, 2016; Molnár et al, 2020; Tuncdemir et al, 2016).…”

“…If these inputs segregate between CA1 pyramids, they converge onto local slm GABAergic interneurons, including NGF cells of the slm . This is reminiscent of the developing neocortex, where layer 1 NGF neurons are first driven by bottom-up inputs, which in turn regulate the establishment of top-down connections from integrative areas (Che et al, 2018; Ibrahim et al, 2021). Whether similar mechanisms operate in the developing CA1 opens an interesting venue for research, this even more given the role of the nucleus reuniens on developmental brain disorders implicating impaired cognitive functions (Cassel et al, 2021; Ferraris et al, 2021; Weel and Witter, 2020).…”