Bellini, Carpaccio, and receptors in the central nervous system.

With the convergence of science from the fields of neurobiology and immunology, many exciting and challenging surprises have emerged regarding cytokines, neuroendocrine hormones, neuropeptides, excitatory amino acids, and their receptors. For some time neurobiologists have known that subsets of neural cells had different receptors for the same ligand. Those subsets of cells could be as different as neurons and astrocytes and as closely related as astrocytes from different lineages or anatomical areas. The neurobiological puzzle has been to determine the functional meaning of these differences. Immunologists in contrast have long understood the clear cut differences between T and B lymphocytes or T helper/inducer and T cytotoxic/suppressor cells and their response to cytokines. However, it is only very recently that they have discovered preferential use by these cells of different receptors for an identical cytokine ligand. Indeed, identical cytokines in the central nervous system and immune response may induce their pleiotropic responses by utilizing different receptors in these two systems. Immunologic paradigms may help neurobiologists predict the existence of subsets of neural cells and their function. Likewise, neurobiology may enable immunologists to predict roles for receptors in gene families as well as the existence of as yet unidentified receptors.     

A matter of focus: monoaminergic modulation of stimulus coding in mammalian sensory networks

Although the presence of neuromodulators in mammalian sensory systems has been noted for some time, a groundswell of evidence has now begun to document the scope of these regulatory mechanisms in several sensory systems, highlighting the importance of neuromodulation in shaping feature extraction at all levels of neural processing. The emergence of more sophisticated models of sensory encoding and of the interaction between sensory and regulatory regions of the brain will challenge sensory neurobiologists to further incorporate a concept of sensory network function that is contingent on neuromodulatory and behavioral state.     

Integration of bimodal looming signals through neuronal coherence in the temporal lobe

The ability to integrate information across multiple sensory systems offers several behavioral advantages, from quicker reaction times and more accurate responses to better detection and more robust learning. At the neural level, multisensory integration requires large-scale interactions between different brain regions--the convergence of information from separate sensory modalities, represented by distinct neuronal populations. The interactions between these neuronal populations must be fast and flexible, so that behaviorally relevant signals belonging to the same object or event can be immediately integrated and integration of unrelated signals can be prevented. Looming signals are a particular class of signals that are behaviorally relevant for animals and that occur in both the auditory and visual domain. These signals indicate the rapid approach of objects and provide highly salient warning cues about impending impact. We show here that multisensory integration of auditory and visual looming signals may be mediated by functional interactions between auditory cortex and the superior temporal sulcus, two areas involved in integrating behaviorally relevant auditory-visual signals. Audiovisual looming signals elicited increased gamma-band coherence between these areas, relative to unimodal or receding-motion signals. This suggests that the neocortex uses fast, flexible intercortical interactions to mediate multisensory integration.     

Functional role of the ventrolateral prefrontal cortex in decision making

To make deliberate decisions, we have to utilize detailed information about the environment and our internal states. The ventral visual pathway provides detailed information on object identity, including color and shape, to the ventrolateral prefrontal cortex (VLPFC). The VLPFC also receives motivational and emotional information from the orbitofrontal cortex and subcortical areas, and computes the behavioral significance of external events; this information can be used for elaborate decision making or design of goal-directed behavior. In this review, we discuss recent advances that are revealing the neural mechanisms that underlie the coding of behavioral significance in the VLPFC, and the functional roles of these mechanisms in decision making and action programming in the brain.     

Condition-dependent chemosignals in reproductive behavior of lizards

This article is part of a Special Issue “Chemosignals and Reproduction”.Many lizards have diverse glands that produce chemosignals used in intraspecific communication and that can have reproductive consequences. For example, information in chemosignals of male lizards can be used in intrasexual competition to identify and assess the fighting potential or dominance status of rival males either indirectly through territorial scent-marks or during agonistic encounters. Moreover, females of several lizard species “prefer” to establish or spend more time on areas scent-marked by males with compounds signaling a better health or body condition or a higher genetic compatibility, which can have consequences for their mating success and inter-sexual selection processes. We review here recent studies that suggest that the information content of chemosignals of lizards may be reliable because several physiological and endocrine processes would regulate the proportions of chemical compounds available for gland secretions. Because chemosignals are produced by the organism or come from the diet, they should reflect physiological changes, such as different hormonal levels (e.g. testosterone or corticosterone) or different health states (e.g. parasitic infections, immune response), and reflect the quality of the diet of an individual. More importantly, some compounds that may function as chemosignals also have other important functions in the organism (e.g. as antioxidants or regulating the immune system), so there could be trade-offs between allocating these compounds to attending physiological needs or to produce costly sexual “chemical ornaments”. All these factors may contribute to maintain chemosignals as condition-dependent sexual signals, which can inform conspecifics on the characteristics and state of the sender and allow making behavioral decisions with reproductive consequences. To understand the evolution of chemical secretions of lizards as sexual signals and their relevance in reproduction, future studies should examine what information the signals are carrying, the physiological processes that can maintain the reliability of the message and how diverse behavioral responses to chemosignals may influence reproductive success.     

The neurobiologist's guide to structural biology: a primer on why macromolecular structure matters and how to evaluate structural data

Structural biology now plays a prominent role in addressing questions central to understanding how excitable cells function. Although interest in the insights gained from the definition and dissection of macromolecular anatomy is high, many neurobiologists remain unfamiliar with the methods employed. This primer aims to help neurobiologists understand approaches for probing macromolecular structure and where the limits and challenges remain. Using examples of macromolecules with neurobiological importance, the review covers X-ray crystallography, electron microscopy (EM), small-angle X-ray scattering (SAXS), and nuclear magnetic resonance (NMR) and biophysical methods with which these approaches are often paired: isothermal titration calorimetry (ITC), equilibrium analytical ultracentifugation, and molecular dynamics (MD).     

啮齿动物的嗅觉通讯研究进展

通过对近40 年来啮齿动物嗅觉通讯的研究综述, 主要介绍嗅觉信号的来源、组成及其对啮齿动物行为生理所产生的作用。啮齿动物嗅觉通讯的信号来源主要是粪便、尿液和特化皮肤腺等, 对这些化学信号的成分分析主要集中在各种信息素(Pheromone) 的结构、来源及其引起的行为反应。目前, 在对啮齿动物嗅觉通讯神经通路的研究中, 对主嗅觉系统和犁鼻器系统在动物嗅觉通讯中的作用仍将是人们研究的重点; 而通过信息素作用所产生的各种行为反应的神经内分泌机制也是动物嗅觉通讯领域研究的热点之一。研究气味信号对动物行为和生理等方面所产生的作用, 将有助于揭示啮齿动物嗅觉通讯在其社会行为中的重要作用。     

Barrels III: Proceedings of a Satellite Symposium of the 1990 Society for Neuroscience Meeting

On October 27 and 28, 1990, approximately 100 somatosensory neurobiologists met in St. Louis, Missouri to discuss the current state of inquiry into the organization of the somatosensory system, emphasizing those portions of the system devoted to processing of inputs from digitized cutaneous organs, such as the rodent mystacial vibrissae. Given the homeomorphic relationship between the vibrissae and cortical and subcortical barrels, a large number of laboratories now employ this model to ask fundamental questions about central processing of sensory inputs, mechanisms controlling topographic pattern formation, and substrates for injury-induced neuronal reorganization. The focus of the third annual Barrels Symposium (Barrels III) was on behavioral aspects of the whisker sense, cholinergic regulation of cortical modules, and genetic and peripheral determinants of barrel development.     

Neuropeptides in insect mushroom bodies

Owing to their experimental amenability, insect nervous systems continue to be in the foreground of investigations into information processing in – ostensibly – simple neuronal networks. Among the cerebral neuropil regions that hold a particular fascination for neurobiologists are the paired mushroom bodies, which, despite their function in other behavioral contexts, are most renowned for their role in learning and memory. The quest to understand the processes that underlie these capacities has been furthered by research focusing on unraveling neuroanatomical connections of the mushroom bodies and identifying key players that characterize the molecular machinery of mushroom body neurons. However, on a cellular level, communication between intrinsic and extrinsic mushroom body neurons still remains elusive. The present account aims to provide an overview on the repertoire of neuropeptides expressed in and utilized by mushroom body neurons. Existing data for a number of insect representatives is compiled and some open gaps in the record are filled by presenting additional original data.     

Combining microscience and neurobiology

There is a wide range of literature on soft lithography, organic surface science (especially self-assembled monolayers of organic thiols adsorbed on gold) and microfluidics. These areas have developed in the fields of physical and surface chemistry, materials science and condensed matter physics, but they offer broad new capabilities in the development of relevant micro- and nanosystems to users in biology in general, and in cell biology in particular. The ability to integrate these techniques for fabricating materials and for controlling the chemistry of surfaces with electrical and electrochemical measurements should be especially relevant in neurobiology. The major impediment to the development of a field of 'microfabrication and measurement' in neuroscience is the absence of effective collaborative interactions between the communities of fabricators and neurobiologists.     

Behavioral and Physiological Analyses of Ultrasound Production by Female Hamsters (Mesocricetus auratus)

The results of behavioral studies suggest specific roles forhigh-frequency vocalizations (ultrasounds) in courtship andcopulatory interactions among golden hamsters. In addition,these results, and functional interpretations based on them,can help to guide studies of physiological mechanisms controllingultrasonic communication. For example, interpretations of rodentultrasounds as sexual or agonistic signals suggest that ultrasoundrates depend on gonadal hormones. This prediction has been verifiedfor several rodent species, including hamsters. Similar reasoningshould apply to the analysis of brain mechanisms for ultrasoundproduction. In particular, the consideration of hamster ultrasoundsas sexual behaviors and vocalizations, as well as hormone-dependentresponses, suggests several brain areas as especially likelyparticipants in neural circuits mediating hormonal effects onultrasonic communication. The preliminary results of a studyin which we lesioned one of these areas, the mesencephalic centralgrey, confirm this structure's involvement in the control ofhamster ultrasounds, and, more generally, support the utilityof behavioral data in physiological studies.     

Sexual ornaments as animal signals

Workers in both animal communication and behavioral ecology have long been interested in animal signals. Animal-communication researchers often have a background in ethology or comparative psychology, and place priority on signal analysis, whereas modern behavioral ecologists are concerned with the effects of natural selection on the exaggeration or development of a trait. Although the two fields examine the same problems, this division has hindered the solution of the problems themselves. Recent theoretical and empirical work has started to bridge the gap, but several important questions, particularly regarding sexual selection, have remained unanswered. Here I examine the differences in these two approaches to the study of animal signals, and suggest additional areas that would benefit by combining the two viewpoints.     

Cerebral Processing of Prosodic Emotional Signals: Evaluation of a Network Model Using rTMS

A great number of functional imaging studies contributed to developing a cerebral network model illustrating the processing of prosody in the brain. According to this model, the processing of prosodic emotional signals is divided into three main steps, each related to different brain areas. The present study sought to evaluate parts of the aforementioned model by using low-frequency repetitive transcranial magnetic stimulation (rTMS) over two important brain regions identified by the model: the superior temporal cortex (Experiment 1) and the inferior frontal cortex (Experiment 2). The aim of both experiments was to reduce cortical activity in the respective brain areas and evaluate whether these reductions lead to measurable behavioral effects during prosody processing. However, results obtained in this study revealed no rTMS effects on the acquired behavioral data. Possible explanations for these findings are discussed in the paper.     

Spontaneous prediction error generation in schizophrenia

Goal-directed human behavior is enabled by hierarchically-organized neural systems that process executive commands associated with higher brain areas in response to sensory and motor signals from lower brain areas. Psychiatric diseases and psychotic conditions are postulated to involve disturbances in these hierarchical network interactions, but the mechanism for how aberrant disease signals are generated in networks, and a systems-level framework linking disease signals to specific psychiatric symptoms remains undetermined. In this study, we show that neural networks containing schizophrenia-like deficits can spontaneously generate uncompensated error signals with properties that explain psychiatric disease symptoms, including fictive perception, altered sense of self, and unpredictable behavior. To distinguish dysfunction at the behavioral versus network level, we monitored the interactive behavior of a humanoid robot driven by the network. Mild perturbations in network connectivity resulted in the spontaneous appearance of uncompensated prediction errors and altered interactions within the network without external changes in behavior, correlating to the fictive sensations and agency experienced by episodic disease patients. In contrast, more severe deficits resulted in unstable network dynamics resulting in overt changes in behavior similar to those observed in chronic disease patients. These findings demonstrate that prediction error disequilibrium may represent an intrinsic property of schizophrenic brain networks reporting the severity and variability of disease symptoms. Moreover, these results support a systems-level model for psychiatric disease that features the spontaneous generation of maladaptive signals in hierarchical neural networks.     

The role of vocal self-stimulation in female responses to males: implications for state-reading

As research neurobiologists, we pursue specific questions, and the answers rendered are also correspondingly specific. Our goal, however, is to understand an entire system or the whole organism. To that end, it is not only useful, but sometimes also necessary, that we periodically reappraise a body of specific data in light of current knowledge of the field at large. In this spirit, the present paper reviews my work on the neural and hormonal mechanisms underlying the reproductive system of ring doves and others' studies of songbirds. By integrating these fields I then advance the concept that inherent in the avian breeding system is the mechanism of "state-reading" (a term fashioned after "mindreading", which was coined by cognitive neuroscientists). State-reading helps to coordinate a sequence of endocrine and behavioral events to realize a desired objective, in this case, successful reproduction.     

Viral Vectors for Gene Delivery and Expression in the CNS

Viral vectors have emerged as an important tool for manipulating gene expression in the adult mammalian brain. The adult brain is composed largely of nondividing cells, and therefore DNA viruses have become the vehicle of choice for neurobiologists interested in somatic gene transfer. Recombinant viral vectors based upon adenovirus or herpes simplex virus have been created in which a gene essential for viral replication is removed and a gene of interest is inserted in the viral genome. While this eliminates pathogenicity due to viral replication, retention of viral genes and continued expression of these genes may limit the potential of the current generation of vectors. Defective viral vectors represent a different approach, in which only viral recognition signals are used to allow packaging of foreign DNA into a viral coat while eliminating the possibility of viral gene expression within target cells. The defective HSV vector has been used to transfer genes into the adult rat brain. This vector has also been used for analysis of the preproenkephalin promoterin vivo,and important regions of this promoter have been identified using this technique. A modification ofin situPCR has been developed as an adjunctive tool for sensitively documenting the presence of vector DNA within target cells duringin vivopromoter studies. Finally, the adenoassociated virus vector has been used as the first fully defective DNA viral vector, which also eliminates any contamination by helper viruses. This vector can transfer genes into the mammalian brain and has shown significant behavioral recovery in a rodent model of Parkinson's disease. Future work will undoubtedly result in still more diverse and improved vectors; however, these studies have documented the importance of viral vectors to both basic neurobiology and the potential treatment of neurologic disease.     

Wiring and rewiring of the retinogeniculate synapse

The formation and refinement of synaptic circuits are areas of research that have fascinated neurobiologists for decades. A recurrent theme seen at many CNS synapses is that neuronal connections are at first imprecise, but refine and can be rearranged with time or with experience. Today, with the advent of new technologies to map and monitor neuronal circuits, it is worthwhile to revisit a powerful experimental model for examining the development and plasticity of synaptic circuits--the retinogeniculate synapse.     

Multimodal Advertisement of Pregnancy in Free-Ranging Female Japanese Macaques (Macaca fuscata)

The role of multiple sexual signals in indicating the timing of female ovulation, and discrimination of this timing by males, has been particularly well studied among primates. However the exhibition of pregnancy signals, and how such signals might modulate male post-conception mating decisions, is still poorly understood. Here we aimed to determine if Japanese macaque males use changes in female sexual signals (behavioral, visual and auditory) to discriminate pregnancy and adjust their socio-sexual behaviors. We combined behavioral observations, digital photography and endocrinological (progestogen and estrogen) data, collected systematically during three one-month periods: the pre-conceptive period, the 1^st month of pregnancy and the 2^nd month of pregnancy. We analyzed variation in the probability of detecting male and female socio-sexual behaviors and estrus calls, as well as changes in female face color parameters, in relation to female reproductive state. Based on our focal observations, we found that males did not copulate during the pregnancy period, and that female socio-sexual behaviors generally decreased from the pre-conceptive to post-conceptive periods. Female face luminance decreased from the pre-conceptive month to the pregnancy period whereas face color only varied between the 1^st and 2^nd month of gestation. Our results suggest that Japanese macaque females display sexual cues of pregnancy that males might use to reduce energy wasted on non-reproductive copulations with pregnant females. We hypothesize that females advertize their pregnancy through changes in behavioral, visual and potential auditory signals that males can use to adjust their mating behaviors. We finish by discussing implications for male and female post-conception strategies.     

Behavioral Isolation Based on Visual Signals in a Sympatric Pair of Darter Species

Elaborate visual communication signals characterize many animal lineages. Often sex‐limited, these signals are generally assumed to result from sexual selection, and in many cases, their evolution is thought to play a central role in speciation. The co‐evolution of male visual signals and female preferences is hypothesized to result in behavioral isolation between divergent lineages; however, for many lineages characterized by elaborate visual signals, the importance of visual differences in behavioral isolation is not well established. Darters (fish genus Etheostoma) are particularly appropriate for examining the role of visual signals in behavioral isolation. They comprise one of the most diverse groups of North American freshwater fish, and nearly every species is characterized by unique nuptial coloration. Multiple darter species co‐exist in sympatric populations, indicating that reproductive barriers are central to maintaining these extraordinarily diverse color patterns. This study demonstrates the presence of behavioral isolation between a pair of distinctly colored sympatric darter species, Etheostoma barrenense and Etheostoma zonale, through experimental observations using an artificial stream. In addition, a series of dichotomous mate‐choice trials indicate that females prefer conspecific males over heterospecifics based on visual differences alone. We therefore provide the first evidence that visual signals are a critical trait maintaining behavioral isolation in darters, a lineage of fishes with spectacular diversification in visual communication.     

The blood-brain barrier in and out of cell culture.

During the past year, the blood-brain barrier has received much attention from neurobiologists and neurologists and real progress has been made in establishing cell-culture model systems that should make future studies more simple. Confusion about the development of the blood-brain barrier, and the exact role of astrocytes in this process persist, but these issues should soon be clarified.