Frontiers in Molecular Neuroscience – résumé and perspective
- 1 Max Delbrück Center for Molecular Medicine, Berlin, Germany
- 2 The School of Pharmacy, London, UK
- 3 Max Planck Institute for Medical Research, Heidelberg, Germany
The open access journal Frontiers in Molecular Neuroscience has existed since 2008. Publications started with an inaugural Research Topic centered on molecular mechanisms of the regulation of excitatory and inhibitory synapses in the brain – also known as E–I balance. This topic addressed the necessity of excitation and inhibition for cognitive function and how both types of transmission need to be co-regulated in order to avoid synaptic dysfunction. De-regulation of the E–I balance is associated with a number of neurological disorders including epilepsy and intellectual disability (Eichler and Meier, 2008; Fritschy, 2008; Harvey et al., 2008; Kehrer et al., 2008). Hence, an understanding of regulatory mechanisms at systemic, network, cellular, and molecular levels is a prerequisite for the development of novel and effective pharmacological therapies. However, we still need to learn and understand how the highly interconnected signaling networks function on a temporal basis, which is required to orchestrate proper brain function. Thus, it is also important to understand synaptic transmission at the level of individual receptors, such as GABAA, glycine, and glutamate receptors (Keith and El-Husseini, 2008; Tretter and Moss, 2008). In addition to synaptic mechanisms, the role of non-synaptic neurotransmitter receptor signaling can also play a fundamental role (Stell and Mody, 2002; Sierra-Paredes and Sierra-Marcuno, 2007; Zhang et al., 2007; Muller et al., 2008; Legendre et al., 2009).
In order to understand how disease-related changes in molecular and cellular mechanisms impact on cognitive processing and brain function in general, it is important to invent experimental tools for targeted manipulation of neuronal activity. In this context, papers focusing on advanced techniques for visualization and manipulation of neuronal activity have helped address unmet needs, placing the journal at the cutting edge of this molecular revolution (Wisden and Meier, 2010). In particular, cell type-selective manipulations of neuronal activity can be achieved with light (Alilain and Silver, 2009; Han et al., 2009; Adamantidis et al., 2010), ligand–receptor combinations (Nichols and Roth, 2009; Wisden et al., 2009), K+ channels (Hodge, 2009), and tethered toxins (Holford et al., 2009). Gene targeting and virally mediated gene expression in mice continues to yield gains (Heldt and Ressler, 2009; Reijmers and Mayford, 2009; Weber et al., 2009). Moreover, model organisms such as Drosophila and zebrafish are increasingly valuable, as they allow rapid generation of transgenic animals or targeted knockdowns and investigation of the systemic changes that result from targeted manipulation of neuronal activity (Kasuya et al., 2009; Tessier and Broadie, 2009; White and Peabody, 2009; Hirata et al., 2010). Molecular systems for monitoring ion flux across the neuronal plasma membrane as well as high-throughput drug screening approaches will also help to develop novel pharmacological tools for treating neurological disorders (Bregestovski et al., 2009; Gilbert et al., 2009; Perron et al., 2009).
Advanced sequencing technologies will play an increasing role in neuroscience, providing us with important information about exomic, genomic, and RNA splice variants. Epigenetic modulation via genomic DNA methylation, regulating gene transcription, is also a rapidly emerging field (Eid et al., 2009; Li et al., 2009; Flusberg et al., 2010). However, it is important to determine whether these polymorphisms, variants, and modifications are relevant to disease. Thus, functional studies that link DNA/RNA polymorphisms or DNA methylation to specific disease states will be required for years to come. A holistic approach involving genomics, RNomics, and proteomics in combination with bioinformatics and computational neuroscience will help create corresponding databases and constitute the basis for multimodal and interdisciplinary views of disease mechanisms. Understanding these multimodal relationships via a multidisciplinary approach should be our primary goal (Engmann and Giese, 2009; Harvey et al., 2009; Legendre et al., 2009; Liebl et al., 2009; Phuket and Covarrubias, 2009; Rivera-Arconada et al., 2009; Poulter et al., 2010).
In summary, the first 3 years of Frontiers in Molecular Neuroscience have been a resounding success, with over 100 articles and 18 Research Topics published to date. The long-term goal of Frontiers in Molecular Neuroscience is to continue publishing the latest findings and conceptual advances in neurobiology (see for example Albrecht, 2011; Carulli et al., 2011; Hideyama and Kwak, 2011; Kaidanovich-Beilin and Woodgett, 2011; Li et al., 2011; Tonges et al., 2011; Weiss, 2011; Zhang et al., 2011). We therefore encourage researchers to submit novel and stimulating findings to Frontiers in Molecular Neuroscience in 2012 and warmly thank all authors and editors for their invaluable support of Frontiers in Molecular Neuroscience.
References
Adamantidis, A., Carter, M. C., and de, L. L. (2010). Optogenetic deconstruction of sleep-wake circuitry in the brain. Front. Mol. Neurosci. 2:31. doi: 10.3389/neuro.02.031.2009
Albrecht, U. (2011). The circadian clock, reward, and memory. Front. Mol. Neurosci. 4:41. doi: 10.3389/fnmol.2011.00041
Alilain, W. J., and Silver, J. (2009). Shedding light on restoring respiratory function after spinal cord injury. Front. Mol. Neurosci. 2:18. doi: 10.3389/neuro.02.018.2009
Bregestovski, P., Waseem, T., and Mukhtarov, M. (2009). Genetically encoded optical sensors for monitoring of intracellular chloride and chloride-selective channel activity. Front. Mol. Neurosci. 2:15. doi: 10.3389/neuro.02.015.2009
Carulli, D., Foscarin, S., and Rossi, F. (2011). Activity-dependent plasticity and gene expression modifications in the adult CNS. Front. Mol. Neurosci. 4:50. doi: 10.3389/fnmol.2011.00050
Eichler, S. A., and Meier, J. C. (2008). E-I balance and human diseases – from molecules to networking. Front. Mol. Neurosci. 1:2. doi: 10.3389/neuro.02.002.2008
Eid, J., Fehr, A., Gray, J., Luong, K., Lyle, J., Otto, G., Peluso, P., Rank, D., Baybayan, P., Bettman, B., Bibillo, A., Bjornson, K., Chaudhuri, B., Christians, F., Cicero, R., Clark, S., Dalal, R., Dewinter, A., Dixon, J., Foquet, M., Gaertner, A., Hardenbol, P., Heiner, C., Hester, K., Holden, D., Kearns, G., Kong, X., Kuse, R., Lacroix, Y., Lin, S., Lundquist, P., Ma, C., Marks, P., Maxham, M., Murphy, D., Park, I., Pham, T., Phillips, M., Roy, J., Sebra, R., Shen, G., Sorenson, J., Tomaney, A., Travers, K., Trulson, M., Vieceli, J., Wegener, J., Wu, D., Yang, A., Zaccarin, D., Zhao, P., Zhong, F., Korlach, J., and Turner, S. (2009). Real-time DNA sequencing from single polymerase molecules. Science 323, 133–138.
Engmann, O., and Giese, K. P. (2009). Crosstalk between Cdk5 and GSK3beta: implications for Alzheimer’s disease. Front. Mol. Neurosci. 2:2. doi: 10.3389/neuro.02.002.2009
Flusberg, B. A., Webster, D. R., Lee, J. H., Travers, K. J., Olivares, E. C., Clark, T. A., Korlach, J., and Turner, S. W. (2010). Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat. Methods 7, 461–465.
Fritschy, J. M. (2008). Epilepsy, E/I balance and GABAA receptor plasticity. Front. Mol. Neurosci. 1:5. doi: 10.3389/neuro.02.005.2008
Gilbert, D. F., Islam, R., Lynagh, T., Lynch, J. W., and Webb, T. I. (2009). High throughput techniques for discovering new glycine receptor modulators and their binding sites. Front. Mol. Neurosci. 2:17. doi: 10.3389/neuro.02.017.2009
Han, X., Qian, X., Stern, P., Chuong, A. S., and Boyden, E. S. (2009). Informational lesions: optical perturbation of spike timing and neural synchrony via microbial opsin gene fusions. Front. Mol. Neurosci. 2:12. doi: 10.3389/neuro.02.012.2009
Harvey, R. J., Carta, E., Pearce, B. R., Chung, S. K., Supplisson, S., Rees, M. I., and Harvey, K. (2008). A critical role for glycine transporters in hyperexcitability disorders. Front. Mol. Neurosci. 1:1. doi: 10.3389/neuro.02.001.2008
Harvey, V. L., Caley, A., Muller, U. C., Harvey, R. J., and Dickenson, A. H. (2009). A selective role for α3 subunit glycine receptors in inflammatory pain. Front. Mol. Neurosci. 2:14. doi: 10.3389/neuro.02.014.2009
Heldt, S. A., and Ressler, K. J. (2009). The use of lentiviral vectors and Cre/loxP to investigate the function of genes in complex behaviors. Front. Mol. Neurosci. 2:22. doi: 10.3389/neuro.02.022.2009
Hideyama, T., and Kwak, S. (2011). When does ALS start? ADAR2-GluA2 hypothesis for the etiology of sporadic ALS. Front. Mol. Neurosci. 4:33. doi: 10.3389/fnmol.2011.00033
Hirata, H., Carta, E., Yamanaka, I., Harvey, R. J., and Kuwada, J. Y. (2010). Defective glycinergic synaptic transmission in zebrafish motility mutants. Front. Mol. Neurosci. 2:26. doi: 10.3389/neuro.02.026.2009
Hodge, J. J. (2009). Ion channels to inactivate neurons in Drosophila. Front. Mol. Neurosci. 2:13. doi: 10.3389/neuro.02.013.2009
Holford, M., Auer, S., Laqua, M., and Ibanez-Tallon, I. (2009). Manipulating neuronal circuits with endogenous and recombinant cell-surface tethered modulators. Front. Mol. Neurosci. 2:21. doi: 10.3389/neuro.02.021.2009
Kaidanovich-Beilin, O., and Woodgett, J. R. (2011). GSK-3: functional insights from cell biology and animal models. Front. Mol. Neurosci. 4:40. doi: 10.3389/fnmol.2011.00040
Kasuya, J., Ishimoto, H., and Kitamoto, T. (2009). Neuronal mechanisms of learning and memory revealed by spatial and temporal suppression of neurotransmission using shibire, a temperature-sensitive dynamin mutant gene in Drosophila melanogaster. Front. Mol. Neurosci. 2:11. doi: 10.3389/neuro.02.011.2009
Kehrer, C., Maziashvili, N., Dugladze, T., and Gloveli, T. (2008). Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia. Front. Mol. Neurosci. 1:6.doi: 10.3389/neuro.02.006.2008
Keith, D., and El-Husseini, A. (2008). Excitation control: balancing PSD-95 function at the synapse. Front. Mol. Neurosci. 1:4. doi: 10.3389/neuro.02.004.2008
Legendre, P., Förstera, B., Jüttner, R., and Meier, J. C. (2009). Glycine receptors caught between genome and proteome – functional implications of RNA editing and splicing. Front. Mol. Neurosci. 2:23. doi: 10.3389/neuro.02.023.2009
Li, H., Foss, S. M., Dobryy, Y. L., Park, C. K., Hires, S. A., Shaner, N. C., Tsien, R. Y., Osborne, L. C., and Voglmaier, S. M. (2011). Concurrent imaging of synaptic vesicle recycling and calcium dynamics. Front. Mol. Neurosci. 4:34. doi: 10.3389/fnmol.2011.00034
Li, J. B., Levanon, E. Y., Yoon, J. K., Aach, J., Xie, B., Leproust, E., Zhang, K., Gao, Y., and Church, G. M. (2009). Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing. Science 324, 1210–1213.
Liebl, C., Panhuysen, M., Putz, B., Trumbach, D., Wurst, W., Deussing, J. M., Muller, M. B., and Schmidt, M. V. (2009). Gene expression profiling following maternal deprivation: involvement of the brain renin-angiotensin system. Front. Mol. Neurosci. 2:1. doi: 10.3389/neuro.02.001.2009
Muller, E., Le-Corronc, H., and Legendre, P. (2008). Extrasynaptic and postsynaptic receptors in glycinergic and GABAergic neurotransmission: a division of labor? Front. Mol. Neurosci. 1:3. doi: 10.3389/neuro.02.003.2008
Nichols, C. D., and Roth, B. L. (2009). Engineered G-protein coupled receptors are powerful tools to investigate biological processes and behaviors. Front. Mol. Neurosci. 2:16. doi: 10.3389/neuro.02.016.2009
Perron, A., Mutoh, H., Akemann, W., Gautam, S. G., Dimitrov, D., Iwamoto, Y., and Knopfel, T. (2009). Second and third generation voltage-sensitive fluorescent proteins for monitoring membrane potential. Front. Mol. Neurosci. 2:5. doi: 10.3389/neuro.02.005.2009
Phuket, T. R., and Covarrubias, M. (2009). Kv4 channels underlie the subthreshold-operating A-type K-current in nociceptive dorsal root ganglion neurons. Front. Mol. Neurosci. 2:3. doi: 10.3389/neuro.02.003.2009
Poulter, M. O., Du, L., Zhurov, V., Palkovits, M., Faludi, G., Merali, Z., and Anisman, H. (2010). Altered organization of GABAA receptor mRNA expression in the depressed suicide brain. Front. Mol. Neurosci. 3:3. doi: 10.3389/neuro.02.003.2010
Reijmers, L., and Mayford, M. (2009). Genetic control of active neural circuits. Front. Mol. Neurosci. 2:27. doi: 10.3389/neuro.02.027.2009
Rivera-Arconada, I., Roza, C., and Lopez-Garcia, J. A. (2009). Enhancing M currents: a way out for neuropathic pain? Front. Mol. Neurosci. 2:10. doi: 10.3389/neuro.02.010.2009
Sierra-Paredes, G., and Sierra-Marcuno, G. (2007). Extrasynaptic GABA and glutamate receptors in epilepsy. CNS Neurol. Disord. Drug Targets 6, 288–300.
Stell, B. M., and Mody, I. (2002). Receptors with different affinities mediate phasic and tonic GABAA conductances in hippocampal neurons. J. Neurosci. 22, RC223.
Tessier, C. R., and Broadie, K. (2009). Activity-dependent modulation of neural circuit synaptic connectivity. Front. Mol. Neurosci. 2:8. doi: 10.3389/neuro.02.008.2009
Tonges, L., Koch, J. C., Bahr, M., and Lingor, P. (2011). ROCKing regeneration: Rho kinase inhibition as molecular target for neurorestoration. Front. Mol. Neurosci. 4:39. doi: 10.3389/fnmol.2011.00039
Tretter, V., and Moss, S. J. (2008). GABAA receptor dynamics and constructing GABAergic synapses. Front. Mol. Neurosci. 1:7. doi: 10.3389/neuro.02.007.2008
Weber, T., Bohm, G., Hermann, E., Schutz, G., Schonig, K., and Bartsch, D. (2009). Inducible gene manipulations in serotonergic neurons. Front. Mol. Neurosci. 2:24. doi: 10.3389/neuro.02.024.2009
Weiss, J. H. (2011). Ca2+ permeable AMPA channels in diseases of the nervous system. Front. Mol. Neurosci. 4:42. doi: 10.3389/fnmol.2011.00042
White, B. H., and Peabody, N. C. (2009). Neurotrapping: cellular screens to identify the neural substrates of behavior in Drosophila. Front. Mol. Neurosci. 2:20. doi: 10.3389/neuro.02.020.2009
Wisden, W., and Meier, J. C. (2010). Genetic techniques and circuit analysis. Front. Mol. Neurosci. 3:4. doi: 10.3389/neuro.02.004.2010
Wisden, W., Murray, A. J., McClure, C., and Wulff, P. (2009). Studying cerebellar circuits by remote control of selected neuronal types with GABAA receptors. Front. Mol. Neurosci. 2:29. doi: 10.3389/neuro.02.029.2009
Zhang, J., Ackman, J. B., Dhande, O. S., and Crair, M. C. (2011). Visualization and manipulation of neural activity in the developing vertebrate nervous system. Front. Mol. Neurosci. 4:43. doi: 10.3389/fnmol.2011.00043
Citation: Meier JC, Harvey RJ and Seeburg P (2011) Frontiers in Molecular Neuroscience – résumé and perspective. Front. Mol. Neurosci. 4:58. doi: 10.3389/fnmol.2011.00058
Received: 15 December 2011;
Accepted: 15 December 2011;
Published online: 30 December 2011.
Copyright: © 2011 Meier, Harvey and Seeburg. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: jochen.meier@mdc-berlin.de