Cre‐expressing neurons in visual cortex of Ntsr1‐Cre GN220 mice are corticothalamic and are depolarized by acetylcholine

Sundberg, Sofie; Lindström, Sivert; Sanchez, Gonzalo M.; Granseth, Björn

doi:10.1002/cne.24323

Cited by 39 publications

(47 citation statements)

References 35 publications

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“…Together, the molecular and connectivity analysis of FOXP2-positive 119 neurons in layer 6 indicate that FOXP2 expression is highly enriched in CT neurons of primary 120 SSC during postnatal development. This is consistent with analysis in primary visual cortex of 121 adult mice, which showed that Foxp2/FOXP2 expression is nearly exclusive to Ntsr1-cre 122 expressing (CT) neurons in the adult (Tasic et al, 2016;Sundberg et al, 2018). The present 123 study builds on previous findings by demonstrating minimal colocalization with two layer 6 CC 124 markers (MET and CCK).…”

supporting

confidence: 87%

FOXP2 exhibits projection neuron class specific expression, but is not required for multiple aspects of cortical histogenesis

Kast

Lanjewar

Smith

et al. 2019

Preprint

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24The expression patterns of the transcription factor FOXP2 in the developing mammalian 25 forebrain have been described, and some studies have tested the role of this protein in the 26 development and function of specific forebrain circuits by diverse methods and in multiple 27 species. Clinically, mutations in FOXP2 are associated with severe developmental speech 28 disturbances, and molecular studies indicate that impairment of Foxp2 may lead to 29 dysregulation of genes involved in forebrain histogenesis. Here, anatomical and molecular 30 phenotypes of the cortical neuron populations that express FOXP2 were characterized in mice. 31Additionally, Foxp2 was removed from the developing mouse cortex at different prenatal ages 32 using two Cre-recombinase driver lines. Detailed molecular and circuit analyses were 33 undertaken to identify potential disruptions of development. Surprisingly, the results 34 demonstrate that Foxp2 function is not required for many functions that it has been proposed to 35 regulate, and therefore plays a more limited role in cortical development than previously 36 thought. 3738 prenatal ages to ascertain its putative roles in the normal histogenic processes that generate the 65 canonical 6 layers, specific cell types based on gene expression, and basic axon targeting to 66 subcortical structures. The results show that FOXP2 expression is limited to specific corticofugal 67 neuron populations and suggest that the gene plays a more limited role in mouse corticogenesis 68 than previously concluded based on results obtained by other experimental methodologies. 69 70 Results 71 Foxp2 expression is enriched in developing corticothalamic projection neurons 72 Initial Foxp2 expression mapping studies determined that Foxp2 transcript and protein 73 expression begin prenatally, with the onset of protein expression delayed relative to the mRNA, 74 and with protein present primarily in postmitotic neurons (Ferland et al., 2003). However, other 75 more recent studies have reported that FOXP2 protein is also expressed in mitotic progenitor 76 cells (Tsui et al., 2013), where it regulates cortical neurogenesis. FOXP2 immunohistochemistry 77 of coronal sections of the embryonic forebrain suggested that FOXP2 protein expression begins 78 between embryonic day (E) 14.5 and E16.5 within postmitotic neurons of the infragranular 79 layers (Figure 1A, B). Postnatally, it is well established that Foxp2 expression is limited to 80 glutamatergic neurons of the infragranular cortical layers, with robust expression predominantly 81 in layer 6 (Ferland et al., 2003; Hisaoka et al., 2010; Sundberg et al., 2018). Layer 6 contains 82 many FOXP2 + neurons, whereas layer 5 contains some FOXP2 + neurons that are more 83 abundant in medial cortical areas at early postnatal stages (Ferland et al., 2003; Campbell et al., 84 2009). Layer 6, where most of the FOXP2+ neurons are located, is comprised of two primary 85 glutamatergic cortical neuron populations, corticothalamic (CT) and corticocortical (CC) neurons 86 (Thomson...

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supporting

confidence: 87%

FOXP2 exhibits projection neuron class specific expression, but is not required for multiple aspects of cortical histogenesis

Kast

Lanjewar

Smith

et al. 2019

Preprint

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“…Investigating how their activity related to arousal level, we found that in the dark, spontaneous population activity of NTSR1 -positive CT neurons was strongly positively correlated with the arousal level of the mouse. Given that these NTSR1 -positive CT neurons are known to be directly depolarized and potently modulated by acetylcholine 41 , in the absence of visual inputs the spontaneous activity that we observed in the dark was likely strongly modulated and/or driven by the cholinergic inputs into V1. Upon drifting grating stimulation, CT population activity correlation with arousal became significantly less than in the dark, possibly because the strong visual inputs that they received from local V1 neurons reduced the influence of and thus the correlation with cholinergic activity.…”

Section: Discussionmentioning

confidence: 84%

A distinct population of L6 neurons in mouse V1 mediate cross-callosal communication

Liang

Sun

et al. 2019

Preprint

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12Through the corpus callosum, interhemispheric communication is mediated by callosal projection (CP) 13 neurons. Using retrograde labeling, we identified a population of layer 6 (L6) excitatory neurons as the 14 main conveyer of transcallosal information in the monocular zone of the mouse primary visual cortex (V1). 15 Distinct from L6 corticothalamic (CT) population, V1 L6 CP neurons contribute to an extensive reciprocal 16 network across multiple sensory cortices over two hemispheres. Receiving both local and long-range 17 cortical inputs, they encode orientation, direction, and receptive field information, while are also highly 18 spontaneous active. The spontaneous activity of L6 CP neurons exhibits complex relationships with brain 19 states and stimulus presentation, distinct from the spontaneous activity patterns of the CT population. The 20 anatomical and functional properties of these L6 CP neurons enable them to broadcast visual and nonvisual 21 information across two hemispheres, and thus play a major role in regulating and coordinating brain-wide 22 activity events. 23 24 25 26 27 28 29 Results 61 CP neurons in mouse V1 are dominantly located in L6 62Traditionally, CP neurons were labeled with intra-parenchymal injection of retrograde tracers, such as 63 horseradish peroxidase or Fluoro-Gold (FG), with varying efficacy 18 . To label CP neurons with high 64 efficacy, we took advantage of a recently developed recombinant AAV variant (rAAV2-retro) that permits 65 efficient retrograde access to projection neurons 19 . We injected rAAV2-retro carrying GFP (rAAV2-66 retro.CAG.GFP) into the monocular zone of right V1 of a transgenic mouse line with L5 excitatory neurons 67 labeled with H2B-mCherry (Rbp4-Cre × Rosa26 LSL CAG H2B mCherry 20 ). We observed brightly labeled 68 CP neurons in the left monocular V1 predominantly located in the cortical layer below L5, with few cells 69 in the supragranular layer (L2/3) ( Figure 1A). More superficial CP neurons were observed at the border of 70 V1 and V2L, consistent with earlier studies 2, 8, 9 . Immunostaining with anti-GABA antibody indicated that 71 these neurons were not GABAergic (Supplementary Figure 1A and 1B). Therefore, CP neurons in mouse 72 V1 are dominantly excitatory neurons located in L6. 73L6 CP neurons and NTSR1-positive CT neurons are distinct populations 74 Having identified L6 neurons as the main callosal-projecting neurons in mouse monocular V1, we then 75 asked whether these CP neurons were distinct from the thalamus-projecting L6 CT neurons. To this end, 76 we utilized a Cre-recombinase transgenic mouse line NTSR1-Cre (NTSR1-cre GN220) that selectively 77 labels L6 CT neurons in V1 21, 22, 23 . Crossed with the Cre reporter line Ai14 24 , the resulting mice had L6 CT 78 neurons expressing red fluorescent protein tdTomato. Injecting rAAV2-retro.syn.GFP in the right V1 and 79 labeling CP neurons in the left hemisphere, we similarly observed that CP neurons were mostly located in 80 L6 (Figure 1B), with high-resolution image stacks ...

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“…We next examined the cell types of Foxp2 and/or Ctip2 expressing cells in layer 6. Since previous retrograde tracing experiments indicated that corticothalamic projection neurons in layer 6 expressed Foxp2 in SCx (Sorensen et al, ) and VCx (Sundberg, Lindström, Sanchez, & Granseth, ) of ∼8‐week old mice, we wondered if this is also the case in young postnatal mice. We injected the Retrobeads into the thalamus at P1 and examined the labeled cells at P5.…”

Section: Resultsmentioning

confidence: 99%

“…Our analysis of retrograde tracing of corticothalamic neurons with the Retrobeads combined with Foxp2 immunostaining at P5 showed that the majority of the labeled cells was Foxp2 + in the three sensory cortexes. We are not aware of any report showing the proportion of Foxp2 + in corticothalamic neurons at this young age, but with about 8‐week old mice, about 30% of corticothalamic neurons expressed Foxp2 in S1 (Sorensen et al, ), and about 85% of corticothalamic neurons are expected to express Foxp2 as about 98% of Ntsr‐1 expressing cells was Foxp2 + , while about 87% of corticothalamic neurons expressed Ntsr‐1 (Sundberg et al, ). No such report on ACx is available yet, but the support comes from our observation that the Foxp2 + band in ACx radially extends dorso‐medially toward VCx in the same coronal sections, where a recent report in VCx indicated the Foxp2 + band likely represents layer 6 (Gray et al, ).…”

Section: Discussionmentioning

confidence: 98%

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

Chang¹,

Suzuki²,

Kawai³

2018

J of Comparative Neurology

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Proper formation of laminar structures in sensory cortexes is critical for sensory information processing. Previous studies suggested that the timing of neuronal migration and the laminar position of cortical neurons differ among sensory cortexes. How they differ during postnatal development has not been systematically investigated. Here, identifying laminas using transcription factors, we examined postnatal changes in neuronal density and distribution in presumptive primary auditory (ACx), visual (VCx), and somatosensory cortexes (SCx) in a strain of mice using immunofluorescence techniques. Development of laminar thickness and its cortical proportion differed among the sensory cortexes. Layers 2-4 defined by Cut-like homeobox 1 (Cux1)-expressing neurons were narrower, and layer 5 was wider in ACx compared to those in VCx or SCx, while Forkhead-box protein P2 (Foxp2)-defined layer 6 was wider in SCx than the other two sensory cortexes throughout postnatal development. Meanwhile, thalamocortical input layers identified by Cux1-expressing neurons formed later in ACx than in the other two cortical regions. The cell densities of ETS-related protein 81-expressing neurons increased in both lower and upper layers but at distinct timing, while those of COUP-TF-interacting protein 2 expressing neurons in the lower layers changed bidirectionally (i.e., increased or decreased) both in layer- and cortical region-specific manners. Foxp2-expressing cells in layer 6 distributed differently and declined at different timing among the sensory cortexes. Overall, we demonstrate that the maturational timing of lamina differs among the sensory cortexes and that postnatal age-dependent changes in neuronal distribution are unique to each of the sensory cortexes.

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Cre‐expressing neurons in visual cortex of Ntsr1‐Cre GN220 mice are corticothalamic and are depolarized by acetylcholine

Cited by 39 publications

References 35 publications

FOXP2 exhibits projection neuron class specific expression, but is not required for multiple aspects of cortical histogenesis

FOXP2 exhibits projection neuron class specific expression, but is not required for multiple aspects of cortical histogenesis

A distinct population of L6 neurons in mouse V1 mediate cross-callosal communication

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

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