New Orleans: the city of Mardi Gras, Cajun cooking, and aboveground graves. From October 25-30, 1997, it was also the center of neuroscience when over 26,000 investigators descended on southern Louisiana to discuss, in the 1997 Society for Neuroscience 27th Annual Meeting, almost every topic a brain could imagine. More than 14,000 individual posters, slide sessions, and lectures were given in 951 separate sections over the course of six very long days. Judging by the crowds in the French Quarter, equally long nights were spent drinking hurricanes (the local drink of choice) in an effort to recuperate from the nonstop, almost frenzied pace of the days' events. As expected from a meeting of this size, a variety of issues were addressed, from normal development and physiology, to the numerous acute and chronic conditions that lead to impaired nervous system functioning. This article is by no means intended as a comprehensive review; rather, keynote lectures and selected presentations are highlighted to give a general sense of the meeting as a whole.

The presentation of data began with the lecture "Stress, Glucocorticoids and Neurodegeneration: Therapies at the Molecular Level, Therapies at the Societal Level," given by Robert Sapolsky of Stanford University. He reviewed glucocorticoid (GC)-mediated toxicity in the hippocampus, and some of the recent advances in gene therapy aimed at ameliorating these effects. He also discussed his research on animal behavior, with the implication that avoiding the release of GCs in the first place is preferable to subsequent molecular interventions.

Sapolsky pointed out that it has been known for many years that long-term exposure to high levels of GCs can be toxic to neurons. Glucocorticoids are released by the adrenal gland in response to stress, leading to effects such as the mobilization of energy and the sharpening of cognition. The physiological purpose of GC release is to survive short-term challenges (i.e., "running for your life"); however, humans tend to become stressed in many different ways, turning on this response chronically. This results in sickness and, more specifically, in damaged neurons.

Aside from direct toxicity, Sapolsky pointed out that GC exposure can lead to an impaired ability to respond to other insults. Glucocorticoids decrease glucose uptake into neurons, leaving cells in energetic crisis due to reduction in ATP levels. Therefore, all the defense mechanisms employed by neurons that require energy become impaired. The functional relevance is not necessarily with everyday stresses, but rather under extreme circumstances. For example, during stroke, neuronal damage can be worsened due to GC released as a stress response.

To combat these effects, Sapolsky's lab has been engaged in experiments involving viral transfer of genes into the hippocampus in experimental models of neurological insult. For example, overexpression of glucose transporter in damage-susceptible neurons can significantly attenuate cell death as measured by cell number, and the saved neurons have been shown to be functional. In addition to energetics, other potential sites of intervention include blocking calcium influx through the overexpression of calbindin, decreasing oxidative damage through overexpression of superoxide dismutase, and decreasing the apoptotic response through expression of Bcl2. Sapolsky indicated that these studies are still in their infancy, with advances needed in the areas of delivery and strength of expression.

The second major talk of the meeting, "Neural Plasticity and the Surprising Function of Recognition Molecules," given by Melitta Schachner of the Zentrum fur Molekulare Neurobiologie Hamburg, also dealt with the hippocampus. Schachner indicated that the roles of neural recognition proteins during development and trauma have been widely investigated; however, a major puzzle relates to the roles of these same proteins during synaptic plasticity. Recent data shows that proteins such as neural cell adhesion molecule (NCAM) are modulated in synapses following generation of long-term potentiation (LTP). Furthermore, interference with NCAM functioning leads to interference with LTP generation and impaired learning. Not surprisingly, NCAM knockout mice also have the same deficiencies in learning and LTP. In addition, these mice demonstrate altered behavior patterns by becoming anxious and aggressive. When these mice were backcrossed to express NCAM 180, a decrease in antisocial behavior was observed in the offspring. Overall, neural recognition molecules such as NCAM and L1 have been shown to be involved in learning and behavior, although we are only at the beginning of understanding their roles in these processes.

Given the implications of NCAMs in learning and hippocampal functioning, some investigators presented data relating to potential glucocorticoid regulation of these proteins. In aging and adrenalectomized rats, Nora Abrous (INSERM) showed that GCs can independently inhibit PSA-NCAM expression and neurogenesis in the rat dentate. This effect on NCAM expression implies the existence of another mechanism mediating glucocorticoid effects on LTP and memory in this brain region.

In major talks such as those described above, presentations were directed at reviewing major advances of the past few years, as well as indicating potential future directions. Poster and slide presentations tended to provide newer data focused on narrower topics. Interestingly, a common theme that appeared in numerous poster and slide sessions was the study of cell death mechanisms. The prevalence of this topic lead Sapolsky to quip during his lecture that he would provide a review slide of apoptotic pathways for the three members of the audience not presenting data on this subject. Whether examining neurodegenerative diseases such as Alzheimer's and Huntington's, or looking at trophic factor effects during development, cell death was everywhere. Many presentations were concerned with the most well-known and conserved aspects of the process, including caspase activation, Bcl2 regulation, and the like. Other studies were concerned with nervous-system-specific events, such as those death signals mediated by the p75 neurotrophin receptor.

Some of the most interesting advances on the mechanisms of apoptosis came from studies examining inhibition of the apoptotic process. For example, data from the lab of Lloyd Greene (Columbia University) demonstrated that transfection of "dominant-negative" cyclin-dependent kinases (cdks) into superior cervical ganglion neurons can block cell death resulting from trophic factor withdrawal and DNA damage. Similarly, the lab of J. Marie Hardwick at The Johns Hopkins University showed that dominant-negative cdk4 or cdk6 can protect neuroblastoma cells from apoptosis induced by viral infection. Further, this latter group hypothesized that the mechanism of this inhibition is related to the ability to block cleavage of the retinoblastoma protein (RB) by caspases. They showed that RB cleavage normally occurs during apoptosis, and this cleavage is most likely a result of caspase 3 activity. By transfecting in mutant cdks, they believe apoptosis is inhibited due to the ability of these cdks to bind RB and shield it from the caspases. These results point to a novel mechanism for potentially interfering with apoptotic processes, and may implicate the retinoblastoma protein as a key regulator of cell death. Studies are currently underway to more directly determine the role of RB in cell death.

Though much of the data at the meeting related to neuronal functioning, numerous studies on other cells of the nervous system, such as glia, were also presented. For example, some recent breakthrough work was detailed on the mechanisms underlying invasive gliomas (those that lead to malignant tumors) and potential targets for treatment of this form of cancer. Susan Hockfield of Yale University related recent work on the CNS extracellular matrix protein BEHAB/brevican. In adults, this protein is a specific marker for invasive gliomas, and indeed seems to mediate the invasive ability. Using an in vitro assay, Hockfield showed that noninvasive gliomas can be made invasive through transfection of the BEHAB/brevican gene. Interestingly, when using transfected cells to form intracranial tumors, only a fragment of the protein (representing a fragment that is normally formed during processing) is able to mediate invasiveness. Overall, these studies implicated three potential target sites for therapeutics: functional ablation of BEHAB, attacking factors that lead to BEHAB expression, and attacking proteins that function in processing this protein.

Other studies examined the characteristics of a chloride channel specific to invasive gliomas. Harald Sontheimer, University of Alabama at Birmingham) believes that this channel may be involved in facilitating migration through narrow pores; that is, by shuttling chloride ions out, the cells may shrink or change shape, thus allowing for movement through small areas. To demonstrate this process, he showed that glioma cells (30 ?m in diameter) can migrate through 5 ?m pores; however, by specifically blocking the channel with chlorotoxin, these cells are unable to migrate. It is the ability of chlorotoxin to bind to these cells that provides an opportunity for therapeutic intervention; either by blocking the channels directly, or using chlorotoxin as a means for targeting therapeutic compounds directly to the glioma.

Underlying many of the advances in development, cell death, learning, oncogenesis, and the myriad of studies presented at this meeting was the goal of determining which gene products may be involved in these processes. During his presentation, James Eberwine of the University of Pennsylvania indicated that many important advances in the future may be discovered by using a single-cell approach. Eberwine pointed out that it is often difficult to do studies in the entire brain, or even specific brain regions when one wants to understand gene regulation at the level of single cells. He then detailed his technique for amplifying RNA from single cells, or particular subcellular regions within cells. This technique is currently used to study cellular responses under various conditions, from activation of a current, to traumatic brain injury. This technology can also be used to compare "normal" neurons to those from patients with diseases such as schizophrenia or ataxias. A major advance in this screening approach is the development of CHIP DNA technology. DNA CHIPS are being created for numerous gene family members, and are becoming increasingly smaller in size. Eberwine envisions a time in the near future when the entire human genome will be arrayed on DNA CHIPS.

Overall, the annual Society for Neuroscience meeting was crowded, overwhelming, tiring, and always stimulating. This overview does not come close to summarizing, or even providing a reasonable approximation of the content of this meeting. There were hundreds of presentations on Alzheimer's disease, section after section on the basal ganglia, and entire symposia on "binocular coordination of eye movements." All of these sections were well attended (though not by myself) and certainly provided interesting data. Indeed, on the third day, no less than CNN itself indicated that the highlight from Sunday's sessions was that rats forced to exercise had impaired immune responses (those glucocorticoids at work again) (Monika Fleshner, University of Colorado at Boulder). Although this was one of the approximately 2,500 presentations I had not seen that day, I was happy to see a fellow neuroscientist gain national recognition, and equally excited that I do not personally face the prospect of forced exercise. However, I did realize that much anxiety was caused by all the hustle, bustle, late nights, early mornings, and general worry that my entire thesis project might show up on someone else's poster. Perhaps next year, someone should begin a study aimed at determining the exact number of neurons we are collectively placing in peril during one of these gatherings . . . on second thought, those results just might stress me out.