3D microphotonic probe for high resolution deep tissue imaging.

Ultra-compact miniaturized optical components for microendoscopic tools and miniaturized microscopes are required for minimally invasive imaging. Current microendoscopic technologies used for deep tissue imaging procedures are limited to a large diameter and/or low resolution due to manufacturing restrictions. We demonstrate a platform for miniaturization of an optical imaging system for microendoscopic applications with a resolution of 1 µm. We designed our probe using cascaded micro-lenses and waveguides (lensguide) to achieve a probe as small as 100 µm x 100 µm with a field of view of 60 µm in diameter. We demonstrate wide-field microscopy based on our polymeric probe fabricated using photolithography and a two-photon polymerization process.

Author Correction: Divergence in the metabolome between natural aging and Alzheimer's disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Divergence in the metabolome between natural aging and Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disorder and one of the leading causes of death in the United States. Although amyloid plaques and fibrillary tangles are hallmarks of AD, research suggests that pathology associated with AD often begins 20 or more years before symptoms appear. Therefore, it is essential to identify early-stage biomarkers in those at risk for AD and age-related cognitive decline (ARCD) in order to develop preventative treatments. Here, we used an untargeted metabolomics analysis to define system-level alterations following cognitive decline in aged and APP/PS1 (AD) mice. At 6, 12, and 24 months of age, both control (Ctrl) and AD mice were tested in a 3-shock contextual fear conditioning (CFC) paradigm to assess memory decline. AD mice exhibited memory deficits across age and these memory deficits were also seen in naturally aged mice. Prefrontal cortex (PFC), hippocampus (HPC), and spleen were then collected and analyzed for metabolomic alterations. A number of significant pathways were altered between Ctrl and AD mice and naturally aged mice. By identifying systems-level alterations following ARCD and AD, these data could provide insights into disease mechanisms and advance the development of biomarker panels.

Microphotonic needle for minimally invasive endoscopic imaging with sub-cellular resolution.

Ultra-compact micro-optical elements for endoscopic instruments and miniaturized microscopes allow for non-invasive and non-destructive examination of microstructures and tissues. With sub-cellular level resolution such instruments could provide immediate diagnosis that is virtually consistent with a histologic diagnosis enabling for example to differentiate the boundaries between malignant and benign tissue. Such instruments are now being developed at a rapid rate; however, current manufacturing technologies limit the instruments to very large sizes, well beyond the sub-mm sizes required in order to ensure minimal tissue damage. We show here a platform based on planar microfabrication and soft lithography that overcomes the limitation of current optical elements enabling single cell resolution. We show the ability to resolve lithographic features that are as small as 2 µm using probes with a cross section that is only 100 microns in size. We also show the ability to image individual activated neural cells in brain slices via our fabricated probe.

Regulation of hippocampal memory traces by neurogenesis.

The hippocampus has long been known as a brain structure fundamental for memory formation and retrieval. Recent technological advances of cellular tracing techniques and optogenetic manipulation strategies have allowed to unravel important aspects of the cellular origin of memory, and have started to shed new light on the neuronal networks involved in encoding, consolidation and retrieval of memory in the hippocampus. In particular, memory traces, or engrams, that are formed during encoding in the dentate gyrus and CA3 region are crucial for memory retrieval and amenable to modulation by neuroplastic mechanisms, including adult hippocampal neurogenesis. Here, we will discuss how memory traces are being encoded at the cellular level, how they may contribute to pattern separation and pattern completion in the hippocampus, and how they can be associated with different experiences to express memories of opposite valence. We propose a mechanism by which adult hippocampal neurogenesis may contribute to the formation of engrams, which may be relevant not only for the encoding of contextual information, but also for mood abnormalities, such as anxiety and depression.