Areal specializations in the morpho-electric and transcriptomic properties of primate layer 5 extratelencephalic projection neurons.

Large-scale analysis of single-cell gene expression has revealed transcriptomically defined cell subclasses present throughout the primate neocortex with gene expression profiles that differ depending upon neocortical region. Here, we test whether the interareal differences in gene expression translate to regional specializations in the physiology and morphology of infragranular glutamatergic neurons by performing Patch-seq experiments in brain slices from the temporal cortex (TCx) and motor cortex (MCx) of the macaque. We confirm that transcriptomically defined extratelencephalically projecting neurons of layer 5 (L5 ET neurons) include retrogradely labeled corticospinal neurons in the MCx and find multiple physiological properties and ion channel genes that distinguish L5 ET from non-ET neurons in both areas.

Input rate encoding and gain control in dendrites of neocortical pyramidal neurons.

Elucidating how neurons encode network activity is essential to understanding how the brain processes information. Neocortical pyramidal cells receive excitatory input onto spines distributed along dendritic branches. Local dendritic branch nonlinearities can boost the response to spatially clustered and synchronous input, but how this translates into the integration of patterns of ongoing activity remains unclear.

GABA-B receptors enhance GABA-A receptor currents by modulation of membrane trafficking in dentate gyrus granule cells.

Activation of postsynaptic GABA-B receptors enhances tonic inhibition mediated by high-affinity extrasynaptic GABA receptors in dentate gyrus granule cells (DGGCs), thalamocortical neurons, and cerebellar granule cells. We investigated the mechanism(s) of GABA current modulation by GABA receptors in DGGCs using a combination of electrophysiological and biochemical approaches. In acute hippocampal brain slices the GABA receptor agonist baclofen increased GABA-evoked currents in ∼2/3rds of DGGCs, significantly increasing GABA currents by 41% on average.

Comparative cellular analysis of motor cortex in human, marmoset and mouse.

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species.