. The projects of the major and minor users in this resubmitted grant application require extensive use of a transmission electron Microscopes (TEM) to obtain information having direct relevance to understanding and treating Alzheimer?s and other neurodegenerative, cerebrovascular and addictive diseases. The biomedical relevance of their efforts is evident from the large number of publications in high impact journals and continuous NIH funding for these investigators. The electron microscopic images used in these publications were collected on the obsolete 28-year-old CM-10 and the 18 year-old Tecnai TEMs. The CM-10 TEM is over the 25-year limit for service contracts and no longer serviced by the manufacturer (FEI). With increasing technical problems and without service, this instrument has become non- functional thereby leaving all the electron microscopic analysis to be conducted on the Tecnai that is frequently out of service owing to malfunctions that reflect both age and heavy usage imposed by the diminished functionality of the CM10. Both these microscopes have an archaic design compared with the newly released Hitachi HT-7800 that has many special features needed for optimal quantitation of immunolabeling in unstained sections taken from laminar- and region-specific brain tissue. These include software-controlled (1) switching between high contrast and high-resolution lens modes, and (2) interfacing the TEM and Mirror CLEM accessory for correlative light and electron microscopic imaging. The HT7800 also has a robust vacuum system that allows for high-throughput and effective time management of users. Due to these considerations, funds are requested to replace the dysfunctional CM10 with a Hitachi HT7800, which is easy to use and well suited for the many diverse projects of major and minor users as well as those of the outside community needing the services of the Microscopic Core within the BMRI. The use of the Hitachi HT7800 for the sophisticated quantification needs should increase the user-time for more basis ultrastructural analysis on the Tecnai by diminishing the excessive demands on the instrument. The time-slot management for each microscope will be assigned by a daily sign-up sheet with long-time allotments being pre-approved by a Local Advisory Committee. The installment of the HT7800 will help to assure a fruitful continuation of the many NIH funded projects involving electron microscopy within the multidisciplinary setting of the BMRI that fulfills the institutional commitment by the provision of essential funds and space to the electron microscope facility.
Funds are requested for the purchase of a modernized transmission electron microscope (TEM) that offers improved on-line quantitation and the generation of high contrast images of brain structures most affected by stroke, Alzheimer's, drug addiction and many other debilitating brain diseases. Advanced software on the new TEM seamlessly controls internal operations of the instrument and correlates the electron microscopic images with light microscopic maps of the brain regions under investigation. The replacement of an outdated TEM within the Brain and Mind Research Institute (BMRI) at Weill Cornell Medicine with a new TEM having these attributes will hasten their long-term goal of gaining better understanding and devising more effective therapeutic approaches for treatment of brain diseases.
