Paula L. Croxson - US grants

Project Summary Impairments in cognitive functions that depend on the prefrontal cortex are a common feature of aging, as well as age-related diseases like Alzheimer's disease (AD). These impairments can reduce quality of life and interfere with daily activities including adherence to medication schedules, thereby resulting in additional effects that impact health in the elderly. A potential strategy to augment prefrontal cortex function is to selectively stimulate basal forebrain projections to the prefrontal cortex, increasing acetylcholine release in the dorsolateral prefrontal cortex and stimulating neuronal mechanisms that underlie normal working memory function. We propose to develop such a strategy in rhesus monkeys, and test its ability to improve cognition. This chemogenetic neuromodulation strategy will use a combination of two viruses: one retrogradely-transported vector containing Cre recombinase into dorsolateral prefrontal cortex and a second Cre-dependent DREADD into basal forebrain. This will selectively target basal forebrain neurons projecting to dorsolateral prefrontal cortex. Once this approach has been tested and validated, we will test whether stimulation of neurons of the primate basal forebrain that project to dorsolateral neocortex is effective in offsetting working memory impairment caused by pharmacological antagonism of acetylcholine. This will provide a critical test in a highly translationally-relevant model of the potential for a neurostimulation intervention, targeted at a discrete neuronal circuit, to improve age-related deficits in cognitive functions of the prefrontal cortex.

This project proposal seeks to build and strengthen an existing program for high school students to perform mentored research during the summer, Brain Research Apprenticeships in New York at Columbia (BRAINYAC). Since 2013, BRAINYAC has trained and prepared 108 high school students from low-resourced neighborhoods in New York City for summer research experiences in neuroscience laboratories at Columbia University in the City of New York. We will provide high school students from underprivileged communities and/or who are under-represented minorities the necessary support for a competitive college application and insight into science research as a career choice. We propose to recruit students through partnerships with youth-serving programs and an inclusive application process. We aim to improve students? scientific knowledge and confidence in key scientific skills through directed training, mentoring and research experience. We will achieve this via the two main parts of the program: (A) A comprehensive training program during the spring that incorporates parental involvement, training sessions focused on science content, critical thinking skills, and communication skills, and orientation sessions to assist students in choosing a mentor and laboratory. These sessions are co-developed and run by a scientist and a science educator. (B) Summer laboratory experiences combined with weekly advisory sessions, a final poster presentation and field trips including a social event and a professional development event at the American Museum of Natural History (AMNH). We aim to support our participants? career development and college applications in STEM fields. We will achieve this through comprehensive support structure to work toward our goal of encouraging students to pursue studies and careers in STEM. We will track our success using a mixed-methods evaluation plan and an alumni engagement program including additional opportunities for alumni. In this way, we will reinforce our participants? intent to pursue studies or careers in science, technology, engineering and math (STEM).