Multifunctional Tetrode-like Drug delivery, Optical stimulation, and Electrophysiology (Tetro-DOpE) probes.

Having reliable tools for recording and manipulating circuit activity are essential to understand the complex patterns of neural dynamics that underlie brain function. We present Tetro-DOpE (Tetrode-like Drug delivery, Optical stimulation, and Electrophysiology) probes that can simultaneously record and manipulate neural activity in behaving rodents. We fabricated thin multifunctional fibers (<50 μm) using the scalable convergence thermal drawing process.

Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice.

Perineuronal nets (PNNs) are densely packed extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. PNNs stabilize synapses inhibiting synaptic plasticity. Here we show that synaptic terminals of fast-spiking interneurons localize to holes in the PNNs in the adult mouse somatosensory cortex.

Using Two-Choice Assay to Study Optogenetics in Hands-On Neurobiology Laboratory Activities.

Optogenetics has made a significant impact on neuroscience, allowing activation and inhibition of neural activity with exquisite spatiotemporal precision in response to light. In this lab session, we use fruit flies to help students understand the fundamentals of optogenetics through hands-on activities. The CsChrimson channelrhodopsin, a light-activated cation channel, is expressed in sweet and bitter sensory neurons.

Increased expression of chondroitin sulfate proteoglycans in dentate gyrus and amygdala causes postinfectious seizures.

Alterations in the extracellular matrix are common in patients with epilepsy and animal models of epilepsy, yet whether they are the cause or consequence of seizures and epilepsy development is unknown. Using Theiler's murine encephalomyelitis virus (TMEV) infection-induced model of acquired epilepsy, we found de novo expression of chondroitin sulfate proteoglycans (CSPGs), a major extracellular matrix component, in dentate gyrus (DG) and amygdala exclusively in mice with acute seizures. Preventing the synthesis of CSPGs specifically in DG and amygdala by deletion of the major CSPG aggrecan reduced seizure burden.

Perineuronal nets support astrocytic ion and glutamate homeostasis at tripartite synapses.

Perineuronal nets (PNNs) are dense, negatively charged extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. Synapses can be embedded and stabilized by PNNs believed to prevent synaptic plasticity. We find that in cortical fast-spiking interneurons synaptic terminals localize to perforations in the PNNs, 95% of which contain either excitatory or inhibitory synapses or both.

Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age.

Astrocytes extend endfeet that enwrap the vasculature, and disruptions to this association which may occur in disease coincide with breaches in blood-brain barrier (BBB) integrity. Here we investigate if focal ablation of astrocytes is sufficient to disrupt the BBB in mice. Targeted two-photon chemical apoptotic ablation of astrocytes induced a plasticity response whereby surrounding astrocytes extended processes to cover vascular vacancies.

Nano-optoelectrodes Integrated with Flexible Multifunctional Fiber Probes by High-Throughput Scalable Fabrication.

Metallic nano-optoelectrode arrays can simultaneously serve as nanoelectrodes to increase the electrochemical surface-to-volume ratio for high-performance electrical recording and optical nanoantennas to achieve nanoscale light concentrations for ultrasensitive optical sensing. However, it remains a challenge to integrate nano-optoelectrodes with a miniaturized multifunctional probing system for combined electrical recording and optical biosensing in vivo. Here, we report that flexible nano-optoelectrode-integrated multifunctional fiber probes can have hybrid optical-electrical sensing multimodalities, including optical refractive index sensing, surface-enhanced Raman spectroscopy, and electrophysiological recording.

Spatially expandable fiber-based probes as a multifunctional deep brain interface.

Understanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires miniaturized neural interfaces that integrate into brain tissue without altering its properties. Existing neural interface technologies have been shown to provide high-resolution electrophysiological recording with high signal-to-noise ratio.

Polymer Composite with Carbon Nanofibers Aligned during Thermal Drawing as a Microelectrode for Chronic Neural Interfaces.

Microelectrodes provide a direct pathway to investigate brain activities electrically from the external world, which has advanced our fundamental understanding of brain functions and has been utilized for rehabilitative applications as brain-machine interfaces. However, minimizing the tissue response and prolonging the functional durations of these devices remain challenging. Therefore, the development of next-generation microelectrodes as neural interfaces is actively progressing from traditional inorganic materials toward biocompatible and functional organic materials with a miniature footprint, good flexibility, and reasonable robustness.

Vascular amyloidosis impairs the gliovascular unit in a mouse model of Alzheimer's disease.

Reduced cerebral blood flow impairs cognitive function and ultimately causes irreparable damage to brain tissue. The gliovascular unit, composed of neural and vascular cells, assures sufficient blood supply to active brain regions. Astrocytes, vascular smooth muscle cells, and pericytes are important players within the gliovascular unit modulating vessel diameters.

Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells.

Astrocytic endfeet cover the entire cerebral vasculature and serve as exchange sites for ions, metabolites and energy substrates from the blood to the brain. They maintain endothelial tight junctions that form the blood-brain barrier (BBB) and release vasoactive molecules that regulate vascular tone. Malignant gliomas are highly invasive tumours that use the perivascular space for invasion and co-opt existing vessels as satellite tumour form.