Layer 1 of somatosensory cortex: An important site for input to a tiny cortical compartment

Abstract

Neocortical layer (L) 1 is a locus for interactions between long-range inputs, L1 interneurons and apical tuft dendrites of pyramidal neurons. Even though we have a wealth of information about L1, the level and effect of local input to this layer have not been quantified. Here we characterized the input to L1 of mouse somatosensory cortex with fast blue, monosynaptic rabies and optogenetics. Our work shows that most of the input to L1 is local, and that both local and long-range inputs to this layer arise predominantly from L2/3 and L5 neurons. Subtypes of L5 and L6b neurons project to the overlying L1 with different probabilities. VIP and SST interneurons in L2/3 and L5 also innervate L1. A subset of local L5, the intratelencephalic, pyramidal neurons, drive L1 interneurons but have no effect on L5 apical tuft dendrites. Monosynaptic rabies-based retrograde labelling reveals presynaptic boutons covering the entire somato-dendritic axis of pyramidal neurons, including in L1. When fast blue application was combined with rabies virus, we found that only a fraction of local and long-range neurons was both presynaptic to L5 neurons and projected to L1. These results demonstrate that L1 receives a large proportion of its input from local neurons, and that some of these inputs specifically target interneurons. We conclude that L1 is not just a site for interaction between long-range feedback and apical tuft dendrites of pyramidal cells, it is also a site for complex modulation of pyramidal neurons and interneurons by local inputs.Significance StatementHere we used traditional retrograde tracing combined with physiology and rabies virus to quantify the connectivity to L1 of somatosensory cortex. We show that local inputs far outweigh long-range inputs. We also show that subtypes of L5 neurons target the overlying L1 and depolarize L1 interneurons but have little effect on the apical tuft dendrites of L5 neurons. Local and long-range cortical inputs to L1 arise from presynaptic neurons in L2/3 and L5. The long-range input arises from a variety of cortical areas including primary motor, secondary somatosensory and motor, perirhinal and visual cortex. Thus, interneurons in L1 and the dendrites of pyramidal neurons are the site of complex interactions with local and long-range inputs.

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).…”

Higher-order thalamic nuclei facilitate the generalization and maintenance of spike-and-wave discharges of absence seizures

“…Alternatively, HO nuclei can potentiate cortical input via projections to the apical tufts of layer V pyramidal cells located in layer I (Ledderose et al, 2021, Diamond ME., 1995. Activation of these dendrites is known to trigger back-propagating calcium spikes that can increase the activity of the pyramidal cells when coincident with feedforward cortico-cortical input (Larkum et al, 2001).…”

Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex

“…NGFC GABAergic (both synaptic and extrasynaptic) and gap junctionmediated transmission depend critically on the spatial properties of the axonal arbor (37,57,58), but the increase in arbor size in human LAMP5 cells (~1.2×) was much less than the 1.6× increase in pyramidal-cell apical dendrite extent in L1. Changes in input sensitivity could enable the conservation of their "blanket" inhibitory function while also permitting some increased spatial and topographic selectivity; NGFC circuit connectivity has been shown to be both tightly controlled (59,60) and to exert strong effects on pyramidal-cell sensory processing (1,6).…”