Inhibitors of ectonucleotidases have paradoxical effects on synaptic transmission in the mouse cortex

We show that the splicing regulator PTBP2 controls a genetic program essential for neuronal maturation. Depletion of PTBP2 in developing mouse cortex leads to degeneration of these tissues over the first three postnatal weeks, a time when the normal cortex expands and develops mature circuits. Cultured Ptbp2−/− neurons exhibit the same initial viability as wild type, with proper neurite outgrowth and marker expression. However, these mutant cells subsequently fail to mature and die after a week in culture. Transcriptome-wide analyses identify many exons that share a pattern of mis-regulation in the mutant brains, where isoforms normally found in adults are precociously expressed in the developing embryo. These transcripts encode proteins affecting neurite growth, pre- and post-synaptic assembly, and synaptic transmission. Our results define a new genetic regulatory program, where PTBP2 acts to temporarily repress expression of adult protein isoforms until the final maturation of the neuron.

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A Platform for Spatiotemporal “Matrix” Stimulation in Brain Networks Reveals Novel Forms of Circuit Plasticity

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.792228 ◽

2022 ◽

Vol 15 ◽

Author(s):

Nathan R. Wilson ◽

Forea L. Wang ◽

Naiyan Chen ◽

Sherry X. Yan ◽

Amy L. Daitch ◽

...

Keyword(s):

Neural Networks ◽

Synaptic Transmission ◽

High Throughput ◽

Brain Networks ◽

Neural Prosthetics ◽

Traditional Methods ◽

Cortical Areas ◽

Precise Timing ◽

Mouse Cortex ◽

Brain Circuit

Here we demonstrate a facile method by which to deliver complex spatiotemporal stimulation to neural networks in fast patterns, to trigger interesting forms of circuit-level plasticity in cortical areas. We present a complete platform by which patterns of electricity can be arbitrarily defined and distributed across a brain circuit, either simultaneously, asynchronously, or in complex patterns that can be easily designed and orchestrated with precise timing. Interfacing with acute slices of mouse cortex, we show that our system can be used to activate neurons at many locations and drive synaptic transmission in distributed patterns, and that this elicits new forms of plasticity that may not be observable via traditional methods, including interesting measurements of associational and sequence plasticity. Finally, we introduce an automated “network assay” for imaging activation and plasticity across a circuit. Spatiotemporal stimulation opens the door for high-throughput explorations of plasticity at the circuit level, and may provide a basis for new types of adaptive neural prosthetics.

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Preplate neurons in embryonic mouse cortex: Ultrastructural observations using photoconversion of the fluorescent lipophilic dye dil

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100124938 ◽

1992 ◽

Vol 50 (1) ◽

pp. 906-907

Author(s):

Linda C. Hassinger ◽

James E. Crandall

Keyword(s):

Mouse Embryos ◽

Embryonic Mouse ◽

Cortical Afferents ◽

Mouse Cortex ◽

Carbocyanine Dye ◽

Increased Sensitivity

We have begun to look directly at small numbers of afferent axons to early generated neurons that form the preplate in the developing mouse cortex. The carbocyanine dye Dil (1’1, dioctadecyl-3,3,3’3’-tetramethyl-indocarbocyanine) has proved especially useful for this goal. DiI labels axons and their terminals with greater sensitivity and without some of the disadvantages of axon filling with HRP. The increased sensitivity provided by labeling embryonic axons with DiI has given us new insights into the development of cortical afferents. For instance, we reported originally that afferents from the thalamus were present below the cortex as early as embryonic day 15 (E15) based on HRP injections into mouse embryos. By using DiI placements into the thalamus in aldehyde-fixed brains, we now know that thalamic fibers reach the cortex 24 hrs earlier.

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