Social interaction is a complex behavior essential for many species, and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically- and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social but not novel-object interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type-1 dopamine receptor signaling downstream in the NAc. Direct observation of projection-specific activity in this way captures a fundamental and previously inaccessible dimension of circuit dynamics.
Brain function depends on simultaneous electrical, chemical and mechanical signaling at the cellular level. This multiplicity has confounded efforts to simultaneously measure or modulate these diverse signals in vivo. Here we present fiber probes that allow for simultaneous optical stimulation, neural recording and drug delivery in behaving mice with high resolution. These fibers are fabricated from polymers by means of a thermal drawing process that allows for the integration of multiple materials and interrogation modalities into neural probes. Mechanical, electrical, optical and microfluidic measurements revealed high flexibility and functionality of the probes under bending deformation. Long-term in vivo recordings, optogenetic stimulation, drug perturbation and analysis of tissue response confirmed that our probes can form stable brain-machine interfaces for at least 2 months. We expect that our multifunctional fibers will permit more detailed manipulation and analysis of neural circuits deep in the brain of behaving animals than achievable before.
Improvements in quantum dot light-emitting device (QD-LED) performance are achieved by the choice of organic charge transporting layers, by use of different colloidal QDs for the different parts of the visible spectrum, and by utilizing a recently demonstrated robust QD deposition method. Spectrally narrow electroluminescence of our QD-LEDs is tuned over the entire visible wavelength range from lambda = 460 nm (blue) to lambda = 650 nm (deep red). By printing close-packed monolayers of different QD types inside an identical QD-LED structure, we demonstrate that different color QD-LEDs with QDs of different chemistry can be fabricated on the same substrate. We discuss mechanisms responsible for efficiency increase for green (4-fold) and orange (30%) QD-LEDs as compared to previous reports and outline challenges associated with achieving high-efficiency blue QD-LEDs.
Exciting nerve cells deep inside the brain Current techniques to stimulate regions inside the brain need a permanently implanted wire or an optical fiber. Working in mice, Chen et al. developed a method to overcome this problem (see the Perspective by Temel and Jahanshahi). They introduced heat-sensitive capsaicin receptors into nerve cells and then injected magnetic nanoparticles into specific brain regions. The nanoparticles could be heated by external alternating magnetic fields, which activated the ion channel–expressing neurons. Thus, cellular signaling deep inside the brain can be controlled remotely without permanent implants. Science , this issue p. 1477 ; see also p. 1418
Cholinergic neurons are widespread, and pharmacological modulation of acetylcholine receptors affects numerous brain processes, but such modulation entails side effects due to limitations in specificity for receptor type and target cell. As a result, causal roles of cholinergic neurons in circuits have been unclear. We integrated optogenetics, freely moving mammalian behavior, in vivo electrophysiology, and slice physiology to probe the cholinergic interneurons of the nucleus accumbens by direct excitation or inhibition. Despite representing less than 1% of local neurons, these cholinergic cells have dominant control roles, exerting powerful modulation of circuit activity. Furthermore, these neurons could be activated by cocaine, and silencing this drug-induced activity during cocaine exposure (despite the fact that the manipulation of the cholinergic interneurons was not aversive by itself) blocked cocaine conditioning in freely moving mammals.
Within the mammalian nervous system, billions of neurons connected by quadrillions of synapses exchange electrical, chemical and mechanical signals. Disruptions to this network manifest as neurological or psychiatric conditions. Despite decades of neuroscience research, our ability to treat or even to understand these conditions is limited by the tools capable of probing the signalling complexity of the nervous system. Although orders of magnitude smaller and computationally faster than neurons, conventional substrate-bound electronics do not address the chemical and mechanical properties of neural tissue. This mismatch results in a foreign-body response and the encapsulation of devices by glial scars, suggesting that the design of an interface between the nervous system and a synthetic sensor requires additional materials innovation. Advances in genetic tools for manipulating neural activity have fuelled the demand for devices capable of simultaneous recording and controlling individual neurons at unprecedented scales. Recently, flexible organic electronics and bio- and nanomaterials have been developed for multifunctional and minimally invasive probes for long-term interaction with the nervous system. In this Review, we discuss the design lessons from the quarter-century-old field of neural engineering, highlight recent materials-driven progress in neural probes, and look at emergent directions inspired by the principles of neural transduction.
Optogenetic interrogation of neural pathways relies on delivery of light-sensitive opsins into tissue and subsequent optical illumination and electrical recording from the regions of interest. Despite the recent development of multifunctional neural probes, integration of these modalities within a single biocompatible platform remains a challenge. Here, we introduce a device composed of an optical waveguide, six electrodes, and two microfluidic channels produced via fiber drawing. Our probes facilitated injections of viral vectors carrying opsin genes, while providing collocated neural recording and optical stimulation. The miniature (< 200 μm) footprint and modest weight (<0.5 g) of these probes allowed for multiple implantations into the mouse brain, which enabled opto-electrophysiological investigation of projections from the basolateral amygdala to the medial prefrontal cortex and ventral hippocampus during behavioral experiments. Fabricated solely from polymers and polymer composites, these flexible probes minimized tissue response to achieve chronic multimodal interrogation of brain circuits with high fidelity.
We demonstrate light emitting devices (LEDs) with a broad spectral emission generated by electroluminescence from a mixed-monolayer of red, green, and blue emitting colloidal quantum dots (QDs) in a hybrid organic/inorganic structure. The colloidal QDs are reproducibly synthesized and yield high luminescence efficiency materials suitable for LED applications. Independent processing of the organic charge transport layers and the QD luminescent layer allows for precise tuning of the emission spectrum without changing the device structure, simply by changing the ratio of different color QDs in the active layer. Spectral tuning is demonstrated through fabrication of white QD-LEDs that exhibit external quantum efficiencies of 0.36% (Commission Internationale de l'Eclairage) coordinates of (0.35, 0.41) at video brightness, and color rendering index of 86 as compared to a 5500 K blackbody reference.
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