On August 29 – 31, 2007, the NIH Blueprint for Neuroscience Research hosted a workshop of approximately thirty leading scientists in the field of neuroplasticity. The participants were charged with discussing and identifying ideas for the most effective tools and resources that can be developed with NIH Blueprint funds to benefit the research community and help advance the field of neuroplasticity. Introductions and plenary lectures took place on the evening of August 29. On August 30, the participants sorted themselves into four breakout groups that represented the major themes that emerged from the ideas the participants brought to the table. These themes were: (a) molecular anatomy; (b) reporting; (c) manipulation; and (d) bridging among different levels and bridging to clinical applications. Each breakout group discussed and identified the highest priority ideas for their domains. On the final morning (August 31), the ideas from each breakout group were presented in a series of Powerpoint presentations in conjunction with examples from recent work.
The highest priority ideas that emerged from the workshop are outlined below. Some of the overlapping ideas that emerged from different breakout groups were consolidated into larger themes.
1. Manipulating and monitoring activity
- Stimulate the development of optical and other hardware to manipulate and monitor activity at multiple loci in the brain including deep structures. Encourage collaborations among investigators in different disciplines to foster innovation. Also, encourage collaborations between researchers and businesses so that early stage research and development take into account important factors such as product effectiveness and ease-of use for the research community.
- Identify novel ways to perturb cellular or molecular signaling functions.
- Stimulate the development of optical and other probes to detect changes in neural activity, e.g. membrane potential, ion concentration, & signaling molecules, recently formed or modified synapses, transcription, translation, endogenous RNA transport, post-translational modifications, mRNA and protein degradation, protein/protein and protein/RNA interactions, etc.
2. Molecular phenotypes of cells
- Assay RNA levels for the complete transcript set of given cell populations using sequencing-by-synthesis technology.
- Assay subcellular distribution of RNAs using in situ hybridization.
- Develop nervous system-specific markers/technologies to identify and monitor experience-induced epigenetic modifications.
4. Better inducible mice
- Address deficiencies in the existing inducible systems for Cre recombinase.
- Develop new systems for site specific recombination.
- Develop wider array of cell-specific promoters.
5. Behavioral phenotyping
- Strengthen and expand facilities for standardization and quality enhancement – extremely useful for labs with a molecular phenotype that need to know behavioral outcome.
- Dissemination of established neuroscience tools
- User-ready viral and plasmid stocks of commonly used reagents such as optical reporters.
- [Also, extended discussion in breakouts of enhanced access to mice.]
- Dissemination of emerging neuroscience tools
- Address lack of incentives/resources to disseminate new technologies
- Funding to support the laborious process of preparing, sharing and sending reagents, protocols and animals
7. Comprehensive analysis of synaptic function and plasticity in animal models of disease
- Determine the synaptic phenotype in various brain regions and use this information to develop therapeutic strategies.
8. Cellular manipulation in primates
- Gene knockdown approaches, refinement of gene targeting strategies, and viral vectors.
9. High throughput screens of synaptic plasticity
- Develop a cell-based assay of synaptic activity and plasticity suitable for high throughput screen format and test with large chemical libraries.
10. Circuit re-training following focal injury of the brain or spinal cord
- Bridge the gap between cellular/synaptic events and plasticity in human imaging studies.
- Develop noninvasive methods for identifying available circuitry after injuries – especially tools for non-invasive circuit analysis in humans – combined stimulation and imaging.
- Identify genetic polymorphisms associated with good vs. bad outcome following injury.
- Develop novel technologies for circuit retraining, such as neuro-robotics & brain stimulation.