Author response for "Laminar distribution of cortical projection neurons to the pulvinar: A comparative study in cats and mice"

The cortical projection to the subcortical pathway underlying the optokinetic reflex was studied using antidromic electrical stimulation in the midbrain structures nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT-DTN) while simultaneously recording from cortical neurons in the superior temporal sulcus (STS) of macaque monkeys. Projection neurons were found in all subregions of the middle temporal area (MT) as well as in the medial superior temporal area (MST). Antidromic latencies ranged from 0.9 to 6 ms with a median of 1.8 ms. There was a strong bias in the population of cortical neurons projecting to the NOT-DTN for ipsiversive stimulus movement (towards the recording side), whereas in the population of cortical neurons not projecting to the NOT-DTN a more or less equal distribution of stimulus directions was evident. Our data indicate that there is no special area in the posterior STS coding for ipsiversive horizontal stimulus movement. Instead, a specific selection of cortical neurons from areas MT and MST forms the projection to the NOT-DTN and as a subpopulation has the same directional bias as their subcortical target neurons. These findings are discussed in relation to the functional grouping of cortical output as an organizational principle for specific motor responses.

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Impaired lipid metabolism in astrocytes underlies degeneration of cortical projection neurons in hereditary spastic paraplegia

Acta Neuropathologica Communications ◽

10.1186/s40478-020-01088-0 ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

Yongchao Mou ◽

Yi Dong ◽

Zhenyu Chen ◽

Kyle R. Denton ◽

Michael O. Duff ◽

...

Keyword(s):

Axonal Transport ◽

Lipid Droplet ◽

Axonal Degeneration ◽

Cholesterol Homeostasis ◽

Projection Neurons ◽

Missense Mutations ◽

Cortical Projection ◽

Hereditary Spastic Paraplegias ◽

Cholesterol Levels ◽

Lipid Droplet Size

AbstractHereditary spastic paraplegias (HSPs) are caused by a length-dependent axonopathy of long corticospinal neurons, but how axons of these cortical projection neurons (PNs) degenerate remains elusive. We generated isogenic human pluripotent stem cell (hPSC) lines for two ATL1 missense mutations associated with SPG3A, the most common early-onset autosomal dominant HSP. In hPSC-derived cortical PNs, ATL1 mutations resulted in reduced axonal outgrowth, impaired axonal transport, and accumulated axonal swellings, recapitulating disease-specific phenotypes. Importantly, ATL1 mutations dysregulated proteolipid gene expression, reduced lipid droplet size in astrocytes, and unexpectedly disrupted cholesterol transfer from glia to neurons, leading to cholesterol deficiency in SPG3A cortical PNs. Applying cholesterol or conditioned medium from control astrocytes, a major source of cholesterol in the brain, rescued aberrant axonal transport and swellings in SPG3A cortical PNs. Furthermore, treatment with the NR1H2 agonist GW3965 corrected lipid droplet defects in SPG3A astrocytes and promoted cholesterol efflux from astrocytes, leading to restoration of cholesterol levels and rescue of axonal degeneration in SPG3A cortical PNs. These results reveal a non-cell autonomous mechanism underlying axonal degeneration of cortical PNs mediated by impaired cholesterol homeostasis in glia.

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Single-cell genomics identifies cell type–specific molecular changes in autism

Science ◽

10.1126/science.aav8130 ◽

2019 ◽

Vol 364 (6441) ◽

pp. 685-689 ◽

Cited By ~ 134

Author(s):

Dmitry Velmeshev ◽

Lucas Schirmer ◽

Diane Jung ◽

Maximilian Haeussler ◽

Yonatan Perez ◽

...

Keyword(s):

Cell Types ◽

Molecular State ◽

Clinical Severity ◽

Projection Neurons ◽

Specific Cell ◽

Cortical Projection ◽

Molecular Changes ◽

Single Nucleus ◽

Gene Expression Studies ◽

Transcriptomic Changes

Despite the clinical and genetic heterogeneity of autism, bulk gene expression studies show that changes in the neocortex of autism patients converge on common genes and pathways. However, direct assessment of specific cell types in the brain affected by autism has not been feasible until recently. We used single-nucleus RNA sequencing of cortical tissue from patients with autism to identify autism-associated transcriptomic changes in specific cell types. We found that synaptic signaling of upper-layer excitatory neurons and the molecular state of microglia are preferentially affected in autism. Moreover, our results show that dysregulation of specific groups of genes in cortico-cortical projection neurons correlates with clinical severity of autism. These findings suggest that molecular changes in upper-layer cortical circuits are linked to behavioral manifestations of autism.

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