Neocortex

Abstract: Mammals adapt to a rapidly changing world because of the sophisticated cognitive functions that are supported by the neocortex. The neocortex, which forms almost 80% of the human brain, seems to have arisen from repeated duplication of a stereotypical microcircuit template with subtle specializations for different brain regions and species. The quest to unravel the blueprint of this template started more than a century ago and has revealed an immensely intricate design. The largest obstacle is the daunting variety of inhibitory interneurons that are found in the circuit. This review focuses on the organizing principles that govern the diversity of inhibitory interneurons and their circuits.

Abstract: Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography—the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.

Abstract: This study examined the temporal profile of ischemic neuronal damage following transient bilateral forebrain ischemia in the rat model of four-vessel occlusion. Wistar rats were subjected to transient but severe forebrain ischemia by permanently occluding the vertebral arteries and 24 hours later temporarily occluding the common carotid arteries for 10, 20, or 30 minutes. Carotid artery blood flow was restored and the rats were killed by perfusion-fixation after 3, 6, 24, and 72 hours. Rats with postischemic convulsions were discarded. Ischemic neuronal damage was graded in accordance with conventional neuropathological criteria. Ten minutes of four-vessel occlusion produced scattered ischemic cell change in the cerebral hemispheres of most rats. The time to onset of visible neuronal damage varied among brain regions and in some regions progressively worsened with time. After 30 minutes of ischemia, small to medium-sized striatal neurons were damaged early while the initiation of visible damage to hippocampal neurons in the h1 zone was delayed for 3 to 6 hours. The number of damaged neurons in neocortex (layer 3, layers 5 and 6, or both) and hippocampus (h1, h3-5, paramedian zone) increased significantly (p less than 0.01) between 24 and 72 hours. The unique delay in onset of ischemic cell change and the protracted increase in its incidence between 24 and 72 hours could reflect either delayed appearance of ischemic change in previously killed neurons or a delayed insult that continued to jeopardize compromised but otherwise viable neurons during the postischemic period.

Abstract: Synchronized oscillations and inhibitory interneurons have important and interconnected roles within cortical microcircuits. In particular, interneurons defined by the fast-spiking phenotype and expression of the calcium-binding protein parvalbumin have been suggested to be involved in gamma (30-80 Hz) oscillations, which are hypothesized to enhance information processing. However, because parvalbumin interneurons cannot be selectively controlled, definitive tests of their functional significance in gamma oscillations, and quantitative assessment of the impact of parvalbumin interneurons and gamma oscillations on cortical circuits, have been lacking despite potentially enormous significance (for example, abnormalities in parvalbumin interneurons may underlie altered gamma-frequency synchronization and cognition in schizophrenia and autism). Here we use a panel of optogenetic technologies in mice to selectively modulate multiple distinct circuit elements in neocortex, alone or in combination. We find that inhibiting parvalbumin interneurons suppresses gamma oscillations in vivo, whereas driving these interneurons (even by means of non-rhythmic principal cell activity) is sufficient to generate emergent gamma-frequency rhythmicity. Moreover, gamma-frequency modulation of excitatory input in turn was found to enhance signal transmission in neocortex by reducing circuit noise and amplifying circuit signals, including inputs to parvalbumin interneurons. As demonstrated here, optogenetics opens the door to a new kind of informational analysis of brain function, permitting quantitative delineation of the functional significance of individual elements in the emergent operation and function of intact neural circuitry.