Laminar Dynamics of Target Selection in the Posterior Parietal Cortex of the Common Marmoset.

The lateral intraparietal area (LIP) plays a crucial role in target selection and attention in primates, but the laminar microcircuitry of this region is largely unknown. To address this, we used ultra-high density laminar electrophysiology with Neuropixels probes to record neural activity in the posterior parietal cortex (PPC) of two adult marmosets while they performed a simple visual target selection task. Our results reveal neural correlates of visual target selection in the marmoset, similar to those observed in macaques and humans, with distinct timing and profiles of activity across cell types and cortical layers. Notably, a greater proportion of neurons exhibited stimulus-related activity in superficial layers whereas a greater proportion of infragranular neurons exhibited significant postsaccadic activity. Stimulus-related activity was first observed in granular layer putative interneurons, whereas target discrimination activity emerged first in supragranular layers putative pyramidal neurons, supporting a canonical laminar circuit underlying visual target selection in marmoset PPC. These findings provide novel insights into the neural basis of visual attention and target selection in primates.

Cell-type-resolved mosaicism reveals clonal dynamics of the human forebrain.

Debate remains around the anatomical origins of specific brain cell subtypes and lineage relationships within the human forebrain1-7. Thus, direct observation in the mature human brain is critical for a complete understanding of its structural organization and cellular origins. Here we utilize brain mosaic variation within specific cell types as distinct indicators for clonal dynamics, denoted as cell-type-specific mosaic variant barcode analysis. From four hemispheres and two different human neurotypical donors, we identified 287 and 780 mosaic variants, respectively, that were used to deconvolve clonal dynamics. Clonal spread and allele fractions within the brain reveal that local hippocampal excitatory neurons are more lineage-restricted than resident neocortical excitatory neurons or resident basal ganglia GABAergic inhibitory neurons. Furthermore, simultaneous genome transcriptome analysis at both a cell-type-specific and a single-cell level suggests a dorsal neocortical origin for a subgroup of DLX1+ inhibitory neurons that disperse radially from an origin shared with excitatory neurons. Finally, the distribution of mosaic variants across 17 locations within one parietal lobe reveals that restriction of clonal spread in the anterior-posterior axis precedes restriction in the dorsal-ventral axis for both excitatory and inhibitory neurons. Thus, cell-type-resolved somatic mosaicism can uncover lineage relationships governing the development of the human forebrain.

Synaptic wiring motifs in posterior parietal cortex support decision-making.

The posterior parietal cortex exhibits choice-selective activity during perceptual decision-making tasks1-10. However, it is not known how this selective activity arises from the underlying synaptic connectivity. Here we combined virtual-reality behaviour, two-photon calcium imaging, high-throughput electron microscopy and circuit modelling to analyse how synaptic connectivity between neurons in the posterior parietal cortex relates to their selective activity. We found that excitatory pyramidal neurons preferentially target inhibitory interneurons with the same selectivity. In turn, inhibitory interneurons preferentially target pyramidal neurons with opposite selectivity, forming an opponent inhibition motif. This motif was present even between neurons with activity peaks in different task epochs. We developed neural-circuit models of the computations performed by these motifs, and found that opponent inhibition between neural populations with opposite selectivity amplifies selective inputs, thereby improving the encoding of trial-type information. The models also predict that opponent inhibition between neurons with activity peaks in different task epochs contributes to creating choice-specific sequential activity. These results provide evidence for how synaptic connectivity in cortical circuits supports a learned decision-making task.