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1.  NSF Workshop Report: Discovering General Principles of Nervous System Organization by Comparing Brain Maps across Species 
Efforts to understand nervous system structure and function have received new impetus from the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Comparative analyses can contribute to this effort by leading to the discovery of general principles of neural circuit design, information processing, and gene-structure-function relationships that are not apparent from studies on single species. We here propose to extend the comparative approach to nervous system ‘maps’ comprising molecular, anatomical, and physiological data. This research will identify which neural features are likely to generalize across species, and which are unlikely to be broadly conserved. It will also suggest causal relationships between genes, development, adult anatomy, physiology, and, ultimately, behavior. These causal hypotheses can then be tested experimentally. Finally, insights from comparative research can inspire and guide technological development. To promote this research agenda, we recommend that teams of investigators coalesce around specific research questions and select a set of ‘reference species’ to anchor their comparative analyses. These reference species should be chosen not just for practical advantages, but also with regard for their phylogenetic position, behavioral repertoire, well-annotated genome, or other strategic reasons. We envision that the nervous systems of these reference species will be mapped in more detail than those of other species. The collected data may range from the molecular to the behavioral, depending on the research question. To integrate across levels of analysis and across species, standards for data collection, annotation, archiving, and distribution must be developed and respected. To that end, it will help to form networks or consortia of researchers and centers for science, technology, and education that focus on organized data collection, distribution, and training. These activities could be supported, at least in part, through existing mechanisms at NSF, NIH, and other agencies. It will also be important to develop new integrated software and database systems for cross-species data analyses. Multidisciplinary efforts to develop such analytical tools should be supported financially. Finally, training opportunities should be created to stimulate multidisciplinary, integrative research into brain structure, function, and evolution.
doi:10.1159/000360152
PMCID: PMC4028317  PMID: 24603302
2.  On the Independent Origins of Complex Brains and Neurons 
Brain, Behavior and Evolution  2009;74(3):177-190.
Analysis of the origin and evolution of neurons is crucial for revealing principles of organization of neural circuits with unexpected implications for genomic sciences, biomedical applications and regenerative medicine. This article presents an overview of some controversial ideas about the origin and evolution of neurons and nervous systems, focusing on the independent origin of complex brains and possible independent origins of neurons. First, earlier hypotheses related to the origin of neurons are summarized. Second, the diversity of nervous systems and convergent evolution of complex brains in relation to current views about animal phylogeny is discussed. Third, the lineages of molluscs and basal metazoans are used as illustrated examples of multiple origins of complex brains and neurons. Finally, a hypothesis about the independent origin of complex brains, centralized nervous systems and neurons is outlined. Injury-associated mechanisms leading to secretion of signal peptides (and related molecules) can be considered as evolutionary predecessors of inter-neuronal signaling and the major factors in the appearance of neurons in the first place.
doi:10.1159/000258665
PMCID: PMC2855278  PMID: 20029182
Evolution of nervous systems; Evolution of neurons; Mollusca; Hemichodata; Basal Metazoa; Cell lineages; Neurotransmitters; Genomes; Ctenophora
3.  Molluscan Memory of Injury: Evolutionary Insights into Chronic Pain and Neurological Disorders 
Brain, Behavior and Evolution  2009;74(3):206-218.
Molluscan preparations have yielded seminal discoveries in neuroscience, but the experimental advantages of this group have not, until now, been complemented by adequate molecular or genomic information for comparisons to genetically defined model organisms in other phyla. The recent sequencing of the transcriptome and genome of Aplysia californica, however, will enable extensive comparative studies at the molecular level. Among other benefits, this will bring the power of individually identifiable and manipulable neurons to bear upon questions of cellular function for evolutionarily conserved genes associated with clinically important neural dysfunction. Because of the slower rate of gene evolution in this molluscan lineage, more homologs of genes associated with human disease are present in Aplysia than in leading model organisms from Arthropoda (Drosophila) or Nematoda (Caenorhabditis elegans). Research has hardly begun in molluscs on the cellular functions of gene products that in humans are associated with neurological diseases. On the other hand, much is known about molecular and cellular mechanisms of long-term neuronal plasticity. Persistent nociceptive sensitization of nociceptors in Aplysia displays many functional similarities to alterations in mammalian nociceptors associated with the clinical problem of chronic pain. Moreover, in Aplysia and mammals the same cell signaling pathways trigger persistent enhancement of excitability and synaptic transmission following noxious stimulation, and these highly conserved pathways are also used to induce memory traces in neural circuits of diverse species. This functional and molecular overlap in distantly related lineages and neuronal types supports the proposal that fundamental plasticity mechanisms important for memory, chronic pain, and other lasting alterations evolved from adaptive responses to peripheral injury in the earliest neurons. Molluscan preparations should become increasingly useful for comparative studies across phyla that can provide insight into cellular functions of clinically important genes.
doi:10.1159/000258667
PMCID: PMC2855280  PMID: 20029184
Aplysia; Evolution; Gene loss; Genome; Injury; Nociceptive sensitization; Memory; Neurological disorders; Pain

Results 1-3 (3)