Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. Here we applied single nucleus RNA-sequencing to perform a comprehensive analysis of cell types in the middle temporal gyrus of human cortex. We identified a highly diverse set of excitatory and inhibitory neuronal types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to similar mouse cortex single cell RNA-sequencing datasets revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of human cell type properties. Despite this general conservation, we also find extensive differences between homologous human and mouse cell types, including dramatic alterations in proportions, laminar distributions, gene expression, and morphology. These species-specific features emphasize the importance of directly studying human brain.

Dendritic spines are morphological specializations that receive synaptic inputs and compartmentalize calcium. In spite of a long history of research, the specific function of spines is still not well understood. Here we review the current status of the relation between morphological changes in spines and synaptic plasticity. Since Cajal and Tanzi proposed that changes in the structure of the brain might occur as a consequence of experience, the search for the morphological correlates of learning has constituted one of the central questions in neuroscience. Although there are scores of studies that encompass this wide field in many species, in this review we focus on experimental work that has analyzed the morphological consequences of hippocampal long-term potentiation (LTP) in rodents. Over the past two decades many studies have demonstrated changes in the morphology of spines after LTP, such as enlargements of the spine head and shortenings of the spine neck. Biophysically, these changes translate into an increase in the synaptic current injected at the spine, as well as shortening of the time constant for calcium compartmentalization. In addition, recent online studies using time-lapse imaging have reported increased spinogenesis. The currently available data show a strong correlation between synaptic plasticity and morphological changes in spines, although at the same time, there is no evidence that these morphological changes are necessary or sufficient for the induction or maintenance of LTP. Still, they highlight once more how form and function go hand in hand in the central nervous system.

Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.

How can neural activity propagate through cortical networks built with weak, stochastic synapses? We find precise repetitions of spontaneous patterns of synaptic inputs in neocortical neurons in vivo and in vitro. These patterns repeat after minutes, maintaining millisecond accuracy. Calcium imaging of slices reveals reactivation of sequences of cells during the occurrence of repeated intracellular synaptic patterns. The spontaneous activity drifts with time, engaging different cells. Sequences of active neurons have distinct spatial structures and are repeated in the same order over tens of seconds, revealing modular temporal dynamics. Higher order sequences are replayed with compressed timing.