Neuroscience Meeting Research Articles

Size matters: formation and function of giant synapses

This symposium took place as a satellite of the Society for Neuroscience Meeting in New Orleans on Friday 12 October 2012, hosted by the Neuroscience Center of Excellence at Louisiana State University and sponsored by The Journal of Physiology and The Physiological Society. The meeting drew together several neuroscience communities with differing perspectives on development and function at large synapses in both mammalian and invertebrate nervous systems, including both CNS synapses and peripheral synapses of the neuromuscular junction (NMJ) and considering both pre- and postsynaptic interfaces. For a synapse, size is a clear predictor of its potential power in influencing the target (Petrof & Sherman, 2013). In most cases, single neurons integrate information from many thousands of synapses, but in some cases (such as the NMJ and the calyx of Held) a very high proportion of the synaptic input arises from one dominant axon terminal. Synaptic physiologists have favoured giant synapses for their accessibility, and much of our knowledge about synaptic transmission has been learned from these giant synapses, including the squid giant synapse and the frog NMJ. The unique accessibility of the NMJ has allowed developmental neurobiologists to elucidate the key factors required for synapse assembly. In recent times, a combination of technical breakthroughs in genetic labelling and imaging methods has illustrated that big is also beautiful, as evidenced by studies in which the formation of individual synapses can be followed in vivo. This series of symposium reviews focuses on the formation and then the function of large synapses across a variety of model systems. They include electrophysiological and imaging studies, with presentations about giant synapses from the NMJ to the retina, and from hippocampus to brainstem. The first review, from Tian & Wu (2013), considers the fly and worm model organisms to examine the molecular mechanisms by which ubiquitination regulates synaptogenesis and axonal responses after nerve injury. The ubiquitination cascade, in conjunction with autophagy, dynamically and specifically controls protein turnover to ensure normal synaptic development, clearance of injured distal axons and regeneration of proximal axons. Holcomb et al. (2013) have exploited the new scanning block-face electron microscopy to reconstruct both synaptic and postsynaptic targets of the calyx of Held synapse in order to ask fundamental questions about the origins of neuronal polarity and the ways in which this can guide the earliest stages of synapse formation. The developmental theme continues with a review of cerebellar climbing fibre synapse development, a well-established and elegant mode of synapse elimination in the mammalian CNS. This model is used here by Kano and colleagues (2013) to demonstrate how regulation of calcium transients is involved in the competitive strengthening or weakening of the synapse and implicated in later phases of elimination. From a functional perspective, synapses with differing synaptic strengths within the same network can perform differing functions. Petrof & Sherman (2013) explored the unique features of two classes of thalamocortical synapses with distinct integrative roles; large glutamatergic synapses predominate in transmission of information, while small glutamatergic synapses serve to modulate cortical function. The series concludes with reviews on transmitter release from some of the most intensely studied synaptic terminals. The strength and reliability of transmission at the NMJ is presented from both amphibian and mammalian viewpoints by Meriney & Dittrich (2013). Then the highly specialized sensory synapses of the ear and eye, which are adapted for high levels of exocytosis, are considered from the perspective of their respective neural codes. Kim et al. (2013) suggest that these data support the notion that single calcium channels can trigger exocytosis of multiple vesicles. The theme of contrasting form and function within synaptic structures is continued by Delvendahl et al. (2013) with the mossy fibre terminals of the hippocampus and cerebellum, where the low release probability of hippocampal mossy fibres contrasts with the high release probability of cerebellar mossy fibres. Finally, Neher & Taschenberger (2013) review the recent literature on intracellular calcium binding at the calyx of Held and present some unresolved questions about the mechanisms regulating the time course of the calcium transient.

Long-term potentiation through calcium-mediated N-Cadherin interaction is tightly controlled by the three-dimensional architecture of the synapse

Poster presentation: Twenty Second Annual Computational Neuroscience Meeting: CNS*2013. Paris, France. 13-18 July 2013. The synaptic cleft is an extracellular domain that is capable of relaying a presynaptically received electrical signal by diffusive neurotransmitters to the postsynaptic membrane. The cleft is trans-synaptically bridged by ring-like shaped clusters of pre- and postsynaptically localized calcium-dependent adhesion proteins of the N-Cadherin type and is possibly the smallest intercircuit in nervous systems [1]. The strength of association between the pre- and postsynaptic membranes can account for synaptic plasticity such as long-term potentiation [2]. Through neuronal activity the intra- and extracellular calcium levels are modulated through calcium exchangers embedded in the pre- and postsynaptic membrane. Variations of the concentration of cleft calcium induces changes in the N-Cadherin-zipper, that in synaptic resting states is rigid and tightly connects the pre- and postsynaptic domain. During synaptic activity calcium concentrations are hypothesized to drop below critical thresholds which leads to loosening of the N-Cadherin connections and subsequently unzips the Cadherin-mediated connection. These processes may result in changes in synaptic strength [2]. In order to investigate the calcium-mediated N-Cadherin dynamics at the synaptic cleft, we developed a three-dimensional model including the cleft morphology and all prominent calcium exchangers and corresponding density distributions [3-6]. The necessity for a fully three-dimensional model becomes apparent, when investigating the effects of the spatial architecture of the synapse [7], [8]. Our data show, that the localization of calcium channels with respect to the N-Cadherin ring has substantial effects on the time-scales on which the Cadherin-zipper switches between states, ranging from seconds to minutes. This will have significant effects on synaptic signaling. Furthermore we see, that high-frequency action potential firing can only be relayed to the Calcium/N-Cadherin-system at a synapse under precise spatial synaptic reorganization.

Sensory dynamics transformation into effective motor behavior

Abstracts from Twenty Second Annual Computational Neuroscience Meeting: CNS*2013 Paris, France. 13-18 July 2013

Denervation-induced dendritic reorganization leads to changes in the electrotonic architecture of model dentate granule cells

Poster presentation: Twenty Second Annual Computational Neuroscience Meeting: CNS*2013. Paris, France. 13-18 July 2013. Neuronal death and subsequent denervation of target areas is a major feature of several neurological conditions such as brain trauma, ischemia or neurodegeneration. The denervation-induced axonal loss results in reorganization of the dendritic tree of denervated neurons. Dendritic reorganization of denervated neurons has been previously studied using entorhinal cortex lesion (ECL). ECL leads to shortening and loss of dendritic segments in the denervated outer molecular layer of the dentate gyrus [1]. However, the functional importance of these long-term dendritic alterations is not yet understood and their impact on neuronal electrical properties remains unclear. Therefore, in this study we analyzed what happens to the electrotonic structure and excitability of dentate granule cells after denervation-induced alterations of their dendritic morphology, assuming all other parameters remain equal. To perform comparative electrotonic analysis we used computer simulations in anatomically and biophysically realistic compartmental models of 3D-reconstructed healthy and denervated granule cells. Our results show that somatofugal and somatopetal voltage attenuation due to passive cable properties was strongly reduced in denervated granule cells. In line with these predictions, the attenuation of simulated backpropagating action potentials and forward propagating EPSPs was significantly reduced in dendrites of denervated neurons. In addition, simulations of somatic and dendritic frequency-current (f-I) curves revealed increased excitability in deafferentated granule cells. Taken together, our results indicate that unless counterbalanced by a compensatory adjustment of passive and/or active membrane properties, the plastic remodeling of dendrites following lesion of entorhinal cortex inputs to granule cells will boost their electrotonic compactness and excitability.

Two generic mechanisms for emergence of direction selectivity coexist in recurrent neural networks

Poster presentation: Twenty Second Annual Computational Neuroscience Meeting: CNS*2013. Paris, France. 13-18 July 2013. In the mammalian visual cortex, the time-averaged response of many neurons is maximal for stimuli moving in a particular direction. Such a direction selective response is not found in LGN, upstream of the visual processing pathway, suggesting that cortical networks play a strong role in the generation of direction selectivity. Here we investigate the mechanisms for the emergence of direction selectivity in the recurrent networks of nonlinear firing rate neurons in layer 4 of V1 receiving the input from LGN. In the model the LGN inputs are characterized by different receptive field positions, and their relative temporal phase shifts are reversed for the stimuli moving in the opposite direction. We propose that two distinct mechanisms result in the neuronal direction selective response in these recurrent networks. The first one is a result of nonlinear feed-forward summation of several time-shifted inputs. The second mechanism is based on the competition between neurons for firing in a winner-take-all regime. Both mechanisms rely on inhibitory interactions in the connectivity matrix of lateral connections, but the second one involves inhibitory loops. Typically, the first mechanism results in lower selectivity values than the second, but the time-course of acquiring direction selective response is faster for the first mechanism. Importantly, the two mechanisms have different input frequency tuning. The first mechanism, based on the nonlinear summation, result in a relatively narrow tuning curve around the preferred frequency of the stimulus in the case of the moving grating. In contrast, the direction selectivity arising from the second mechanism depends only weakly on the input frequency, i.e. has a broader tuning curve. These differences allow us to provide the recipe for identifying in experiment which of the two mechanisms is used by a given direction selective neuron. We then analyze how the statistics of the connections in the random recurrent networks affect the relative contributions from these two mechanisms and determine the distributions of the direction selectivity values. We identify the motifs in the connectivity matrix, which are required for each mechanism and show that the minimal conditions for both mechanisms are met in a very broad set of random recurrent networks with sufficiently strong inhibitory connections. Thus, we propose that these mechanisms coexist in generic recurrent networks with inhibition. Our results may account for the recent experimental observations that direction selectivity is present in dark-reared mice and ferrets [1,2]. It can also explain the emergence of direction selectivity in species lacking a spatially organized direction selectivity map.

The BRAIN Initiative: Toward a Chemical Connectome

On April 2, 2013, I had the honor of visiting the White House for President Obama’s announcement of the BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies; http://www.whitehouse.gov/infographics/brain-initiative). Earlier dubbed the BAM (Brain Activity Map) Project, this multiyear nationwide effort has been renamed to reflect its emphasis on technology, and particularly nanotechnology.1 Developing advanced technologies is expected to lead to new ways of investigating complex problems associated with understanding brain function. As it was originally conceived, the BAM Project was focused on creating large-scale functional maps of brain activity in the form of simultaneously measuring action potentials or intracellular Ca2+ concentrations from large numbers of interconnected neurons.2 The development and use of recording and imaging technologies for massively parallel measurements was envisioned to lead to large data sets that could be used by neuroscientists and computational scientists to uncover emergent properties associated with neuronal circuitry. The objective was to advance fundamental understanding of how information is encoded in brains. Focusing solely on neuronal electrical activity is shortsighted if the goal is to understand information processing in brains. Brain function integrally entails complex synaptic chemistries. These chemistries are maintained at enormous costs in terms of protein synthesis, for example, neurotransmitter synthetic and degrading enzymes, synaptic machinery for exocytosis, and diverse receptor proteins. Energy requirements needed to maintain membrane potentials, which drive reuptake of synaptic transmitters, in addition to action potentials, are also costly from a biological perspective. The trade-off is a chemical diversity that provides for tremendous richness in terms of the information content inherent in interneuronal signaling. Chemical signaling underlies G-protein-coupled receptors (GPCRs) and their effects on circuitry remodeling but also ligand-gated ion channels and direct effects of GPCRs on membrane excitability. Thus, a BRAIN Initiative that envisions that emergent properties will be uncovered simply by measuring action potentials of ever increasing numbers of neurons without taking into consideration information inherent (and currently unknown) in complex chemical signaling is grossly oversimplified. Information processing in brains ultimately also resides in dynamic changes in neurotransmitter diffusion gradients combined with spatially complex and tightly controlled patterns of receptor protein expression. This special issue of ACS Chemical Neuroscience arises from the biennial International Society of Monitoring Molecules in Neuroscience Meeting (http://www.monitoringmolecules.org/), which was most recently held in September 2012 in London. The issue provides timely and poignant reminders of the central roles played by chemical neurotransmission in brain function, dysfunction, and the treatment of disorders. On the whole, the issue highlights how far we have come in terms of our understanding of chemical signaling but also how far we have yet to go. New tools fuel fundamentally new conceptualizations. By and large, today’s approaches for sensing neurotransmitters are not able to approach chemical neurotransmission at the scales that will ultimately be important for uncovering emergent properties. Likewise, most methods are not highly multiplexed such that the interplay of multiple chemical transmitters can be unraveled. In addition to measuring electrical activity at hundreds or thousands of neurons simultaneously, we need to advocate for a large-scale multidisciplinary effort aimed at in vivo nanoscale chemical sensing.3 This vision entails developing chemical sensors that are small (recording at the level of synapses), fast (on par with time frames of release/reuptake), chemically selective (can readily distinguish among closely related neurotransmitters), and multiplexed (record changes in multiple neurotransmitters simultaneously). As we celebrate our current accomplishments in elucidating molecular mechanisms of chemical neurotransmission featured in this month’s issue of ACS Chemical Neuroscience, I invite you to look toward the future. The editors at ACS Chemical Neuroscience welcome your views on developing a vision for a chemical connectome. We look forward to publishing your advances in understanding chemical transmission. The International Society for Monitoring Molecules in Neuroscience Meeting similarly welcomes your input and participation regarding programming for its upcoming meeting, which will be held at the University of California, Los Angeles in the summer of 2014.

Epilepsy therapy: anticonvulsants, lessons learned and unmet medical needs

Interview by Rona Williamson, Commissioning EditorHenrik Klitgaard, PhD, is currently Vice-President, UCB Fellow, Neurosciences Therapeutic Area and is based in Braine-l’Alleud, Belgium. He received a PhD in Human Physiology in 1989 at the August Krogh Institute at the University of Copenhagen (Denmark). During his university career, Klitgaard worked at the Pasteur Institute in Paris (France) and at Harvard University (MA, USA). Klitgaard is a leading figure in the epilepsy research community, thanks to more than 80 peer-reviewed papers and 15 reviews and book chapters, as well as frequent lectures at top neuroscience and epilepsy science meetings. His memberships and accolades include a position on the US National Institute of Health’s epilepsy advisory committee, membership of the Neurobiology Committees of both the International League Against Epilepsy and American Epilepsy Society and a seat on the Scientific Advisory Committee of the patient organization C.U.R.E. (Citizens United for Research in Epilepsy). For more than two decades, Klitgaard has conducted antiepileptic drug discovery in the pharmaceutical industry. He has contributed numerous publications on basic and applied aspects of epilepsy research and has frequently been an invited speaker at epilepsy congresses and meetings. During his career in the pharmaceutical industry, Klitgaard has been involved in the discovery and development of antiepileptic drugs at both Novo Nordisk A/S and UCB Pharma. He is also currently involved in the development of two clinical and several preclinical AED candidates.

Motor Recovery after Spinal Cord Injury Enhanced by Strengthening Corticospinal Synaptic Transmission

The corticospinal tract is an important target for motor recovery after spinal cord injury (SCI) in animals and humans. Voluntary motor output depends on the efficacy of synapses between corticospinal axons and spinal motoneurons, which can be modulated by the precise timing of neuronal spikes. Using noninvasive techniques, we developed tailored protocols for precise timing of the arrival of descending and peripheral volleys at corticospinal-motoneuronal synapses of an intrinsic finger muscle in humans with chronic incomplete SCI. We found that arrival of presynaptic volleys prior to motoneuron discharge enhanced corticospinal transmission and hand voluntary motor output. The reverse order of volley arrival and sham stimulation did not affect or decreased voluntary motor output and electrophysiological outcomes. These findings are the first demonstration that spike timing-dependent plasticity of residual corticospinal-motoneuronal synapses provides a mechanism to improve motor function after SCI. Modulation of residual corticospinal-motoneuronal synapses may present a novel therapeutic target for enhancing voluntary motor output in motor disorders affecting the corticospinal tract.

Stephen G Holtzman

Stephen G Holtzman

International Cognitive Neuroscience Meeting, Cognitive-IX, Abstracts, April 13-15, 2012, İstanbul

International Cognitive Neuroscience Meeting, Cognitive-IX, Abstracts, April 13-15, 2012, İstanbul

Methamphetamine‐Induced Locomotor Sensitization in C57BL/6 Mice Requires the MT1 Melatonin Receptor

Genetic deletion of both MT1 and MT2 melatonin receptors abrogates the development and expression of locomotor sensitization in melatonin proficient C3H/HeN mice repeatedly pretreated with methamphetamine (METH) (Hutchinson et al., Program 669.12. 2010 Neuroscience Meeting Planner). However, C57BL/6 mice deficient in pineal melatonin do not develop or express sensitization using the same METH treatment paradigm. Here we assessed the role of MT1 melatonin receptors in locomotor sensitization using a two METH injection protocol. Mice were pretreated with either vehicle or METH (1.2 mg/kg, i.p.) on Day 1, then challenged on Day 8 with METH (1.2 mg/kg, i.p.). On Day 1 METH increased locomotor activity in both WT [60.6±5.5 meters traveled (n=12), p<0.05] and MT1KO mice [57.1±6.5 m (n=12), p<0.05] when compared to vehicle‐treated controls [15.6±4.4 m (n=12), 11.9±1.5 m (n=12) respectively]. METH challenge triggered a sensitized response in METH‐pretreated WT mice [106.0±5.2 m (n=12), p<0.05], but not in METH‐pretreated MT1KO mice [57.1±6.5 (n=12), p>0.05] compared to corresponding vehicle‐pretreated controls [63.2±7.5 m (n=12), 53.1±5.0 m (n=12) respectively]. Our results indicate that in C57BL/6 mice, the expression of the MT1 receptor is required for the induction of METH‐induced sensitization after a single METH pretreatment. Supported by DA021870 to MLD.

News from the Society for Neuroscience Meeting: New Evidence for the Distinct Brain Pathophysiology of Mood Disorders

News from the Society for Neuroscience Meeting: New Evidence for the Distinct Brain Pathophysiology of Mood Disorders

ACS Chemical Neuroscience in 2012: Opportunities and Challenges

Year three of publication of ACS Chemical Neuroscience is upon us—how quickly time flies. Once again, I would like to thank the Associate Editors, Arthur Christopoulos (Monash University) and Alan Jasanoff (MIT), for all of their hard work and volume of manuscripts handled last year—we saw a large increase in submissions. As always, ACS editorial staff have been amazing, and marketing for ACS Chemical Neuroscience has been present at most major neuroscience meetings. Moving into year three, the Journal welcomes Anne M. Andrews (UCLA) as a new Associate Editor, bringing complementary expertise in neuroscience to the editorial board—welcome Anne! We also anticipate three Special Issues in 2012 with Associate Editors Arthur Christopoulos (Monash University) and Alan Jasanoff (MIT), and Benjamin Cravat (SCRIPPS) serving as Guest Editors for their respective Special Issues. We are also planning a thematic crossover with both ACS Medicinal Chemistry Letters and the Journal of Medicinal Chemistry—more on this next month. Moreover, ACS Chemical Neuroscience wants to extend a warm welcome to the new Editors-in-Chief of the Journal of Medicinal Chemistry, Shaomeng Wang and Gunda Georg, and a fond farewell and deep thanks to Philip Portoghese, who made JMC the best medicinal chemistry journal in the world and paved the way for the biological journals within the ACS. Finally, during year three of the Journal, we will learn of the initial Impact Factor. While we can only speculate, based on citations (an ∼7-fold increase in citations in 2011 over 2010), h-index (ACS Chemical Neuroscience has an h-index of 8), and other parameters, we are expecting an impressive Impact Factor for the first neuroscience journal in the American Chemical Society Publications family. 2011 has been a year of major challenges for CNS research, with several major pharmaceutical companies announcing they were leaving altogether and/or significantly downsizing CNS drug discovery. Fortunately, academic drug discovery groups are emerging with CNS focus, and NIH has developed new RFAs to fund drug discovery as well as the highly successful Molecular Libraries Probe Production Center Network (MLPCN). However, lower pay-lines for grant funding continue to put a strain on academics and slow neuroscience research. Importantly, many foundations fund neuroscience research, and many have focused drug discovery funding opportunities—all of these can be found on the ACS Chemical Neuroscience Web site. A huge development at the end of 2011 was the announcement that Congress will fund the National Center for Advancing Translational Sciences (NCATS), and the existing network of Clinical Translational Science Awards (CTSAs) will be brought into NCATS. Hopefully, this will foster new avenues for CNS drug discovery in the academic sector, with full translation into clinical studies. Both the MLPCN and NCATS are necessary to continue innovation in CNS research and therapeutics development in light of the departure of big pharma. In closing, there is a special session entitled Chemical Neuroscience within the Organic Division at the 2012 Spring ACS Meeting in San Diego. The Session features authors and Editors of ACS Chemical Neuroscience and other notable neuroscientists. Please stop by for the session and visit the ACS Chemical Neuroscience booth. 2012 promises to be an important and pivotal year for chemical neuroscience, CNS drug discovery, and ACS Chemical Neuroscience.

News from the Society for Neuroscience Meeting: The Impact of Inflammation on the Unhealthy and Healthy Aging Brain

News from the Society for Neuroscience Meeting: The Impact of Inflammation on the Unhealthy and Healthy Aging Brain

A model study for causal relationships between voltage and calcium dynamics

From Twentieth Annual Computational Neuroscience Meeting: CNS*2011 Stockholm, Sweden. 23-28 July 2011

Online video tracking for activity-dependent stimulation in neuroethology

Poster presentation from Twentieth Annual Computational Neuroscience Meeting: CNS*2011. Stockholm, Sweden. 23-28 July 2011

Quantification of fairness bias by a Fairness-Equity Model

Article accompanying a poster presentation for the 2011 Computational Neuroscience Meeting. This article discusses the quantification of fairness bias by a fairness-equity model.

Scientists Look to Emerging Technology to Treat Chronic Neurological Disorders

SAN DIEGO—Scientists are finding potential therapies for chronic neurological disorders such as stroke and retinal degeneration by harnessing new technologies and a burgeoning understanding of human neurology. Despite advances in neuroscience, cures for many chronic neurological conditions have proven elusive, leading scientists and clinicians to focus on potential rehabilitative therapies. To achieve this, many researchers are working to harness emerging electronic, computer, and molecular technologies to more specifically target the underlying genetic, molecular, and physiological deficits experienced by patients. At the Neuroscience Meeting in San Diego in November, numerous scientists presented evidence that nextgeneration prosthetics and computerassisted interactive therapies may improve function in persons with neurological conditions or in animal models of such disorders. Researchers showed, for example, that a noninvasive artificial retina could help restore near-normal vision in mice with damaged retinas, that virtual reality coupled with physical therapy techniques could help stroke patients improve hand function, and that healthy volunteers and patients being treated for cocaine addiction can be trained to use thoughts to control a computer cursor.

Statistical Analysis of Multi-Cell Recordings: Linking Population Coding Models to Experimental Data

Statistical Analysis of Multi-Cell Recordings: Linking Population Coding Models to Experimental Data

The Last Issue of Our Inaugural Year: Reflections and a View to the Future

Let me open by thanking all the authors and contributors to ACS Chemical Neuroscience in our first year. The content and quality of the articles, letters, reviews, and viewpoints have been exceptional—some truly amazing neuroscience has been published. Submissions in all the major areas the journal hopes to cover are increasing, and international submissions are similarly on the rise. In addition, we witnessed a nice balance of manuscripts from both academia and industry in 2010. Indexing in PubMed is on the horizon—a frequently asked question—and one that just requires time for a new journal. Rest assured, all is proceeding as quickly as possible. Ani, Jennifer, Tara, and all the staff at ACS have done a phenomenal job aiding both myself and the associate editors as well as in promoting the journal at dozens of meetings and conferences. There is a phenomenal team behind this journal—thank you all—the ACS team and the Associate Editors, Arthur and Allan. Serving as Editor-in-Chief for ACS Chemical Neuroscience is amazing—I love this job—I love having my finger on the pulse of emerging neuroscience—I read every submission. What a phenomenal year 2010 proved to be and how very challenging. As most of you know, our 18 month old daughter Paige was diagnosed with stage II neuroblastoma in September, and this CNS disorder was the subject of the last editorial (1). I and my family were overwhelmed by the support and outpouring of concern generated by that piece—though that was not the intention. At the time I wrote the editorial, it was therapeutic for me, and I wanted to bring attention to a rare and neglected disease that is a CNS disorder that matures into a malignant cancer (2). Moreover, significantly more research and attention needs to be directed at neuroblastoma and other diseases of the sympathetic nervous system. The standard of care has changed little in the past 25 years. I am happy to report that Paige is cancer free! We enrolled her in a clinical trial where she received only two rounds of chemotherapy (versus the standard four). During the two cycles, there were problems—ER trips for fevers, vancomycin infusions for possible PICC line infections, and as anticipated, though hard to witness, Paige lost all of her hair by the end. However, CT scans demonstrated more than a 50% reduction in the volume of the tumor, which allowed for a full surgical resection, with clean margins. Paige was back on her feet within two days of surgery. However, the Horner’s Syndrome (3), which initially clued us in to the tumor, is more pronounced. Sympathetic nerves were cut during the resection, so we will have to wait and see if the symptoms diminish over time as the inflammation subsides and nerves regenerate. Our family’s battle with cancer was fortunately very short; however, during the ordeal, we met many families whose children are fighting prolonged, losing battles. Despite the prognosis, the children are so strong and positive—truly inspiring, yet heartbreaking. Now, ACS Chemical Neuroscience in 2011—where are we going? To begin with, I am happy to announce that Dr. Corey Hopkins (research professor of pharmacology at Vanderbilt University Medical Center and associate director of medicinal chemistry for the Vanderbilt Program in Drug Discovery) will be joining the editorial team of ACS Chemical Neuroscience in the role of Managing Editor in January. A regular contributor of Chemical Spotlight features and author, in his new role Corey will work with me to solicit reviews and manuscripts and ensure a presence for the journal at all relevant neuroscience meetings. As always, we are both happy to receive proposals for Chemical Spotlights, Viewpoints, and Reviews—keep them coming. The first issue of 2011 is an all-review issue focused on the chemical senses, and composed by thought leaders in the field—guaranteed to be a good and informative read. Moving forward, all issues will feature a review article, chemical spotlight, viewpoint(s), letters, and full articles. There are plans for thematic issues—at least two in 2011—more on that next month. Also in 2011 is a new feature: “Reflections and a View to the Future” wherein thought leaders across all areas of neuroscience have agreed to write a three page essay describing the state of neuroscience early in their careers, their perspective on the current state of neuroscience, and their views on where the field will move in the future. I am really excited about this new feature and the willingness of over 40 leading neuroscientists to contribute. 2011 is shaping up to be a great year for ACS Chemical Neuroscience—thanks again to everyone for making the journal’s launch successful. ACS Chemical Neuroscience is filling a niche and linking synthetic chemists with neuroscientists to create a new community of chemical neuroscientists to tackle translational research problems—join us.