CiteULike: awooga's library [656 articles]

Selection Type Theories

Lindley Darden — 2008-07-03T03:50:49-00:00

Philosophy of Science, Vol. 56, No. 1. (1989), pp. 106-129.

Selection type theories solve adaptation problems. Natural selection, clonal selection for antibody production, and selective theories of higher brain function are examples. An abstract characterization of typical selection processes is generated by analyzing and extending previous work on the nature of natural selection. Once constructed, this abstraction provides a useful tool for analyzing the nature of other selection theories and may be of use in new instances of theory construction. This suggests the potential fruitfulness of research to find other theory types and construct their abstractions.

A cooperative switch determines the sign of synaptic plasticity in distal dendrites of neocortical pyramidal neurons.

PJ Sjöström — 2006-09-05T18:42:25-00:00

Neuron, Vol. 51, No. 2. (20 July 2006), pp. 227-238.

Pyramidal neurons in the cerebral cortex span multiple cortical layers. How the excitable properties of pyramidal neuron dendrites allow these neurons to both integrate activity and store associations between different layers is not well understood, but is thought to rely in part on dendritic backpropagation of action potentials. Here we demonstrate that the sign of synaptic plasticity in neocortical pyramidal neurons is regulated by the spread of the backpropagating action potential to the synapse. This creates a progressive gradient between LTP and LTD as the distance of the synaptic contacts from the soma increases. At distal synapses, cooperative synaptic input or dendritic depolarization can switch plasticity between LTD and LTP by boosting backpropagation of action potentials. This activity-dependent switch provides a mechanism for associative learning across different neocortical layers that process distinct types of information.

The art of the probable: system control in the adaptive immune system.

RN Germain — 2007-04-29T10:00:26-00:00

Science, Vol. 293, No. 5528. (13 July 2001), pp. 240-245.

The immune system provides very effective host defense against infectious agents. Although many details are known about the cells and molecules involved, a broader "systems engineering" view of this complex system is just beginning to emerge. Here the argument is put forward that stochastic events, potent amplification mechanisms, feedback controls, and heterogeneity arising from spatially dispersed cell interactions give rise to many of the gross properties of the immune system. A better appreciation of these underlying features will not only add to our basic understanding of how immunity develops or goes awry, but also illuminate new directions for manipulating the system in prophylactic and therapeutic settings.

Reflections on the clonal-selection theory

Melvin Cohn — 2007-10-04T05:01:59-00:00

Nature Reviews Immunology, Vol. 7, No. 10., pp. 823-830.

Beyond Neurotransmission: Neuromodulation and its Importance for Information Processing: Neuromodulation and Its Importance for Information Processing

2008-06-28T07:44:00-00:00

(05 August 1999)

This book provides the foundations for understanding the cellular and molecular basis for neuromodulatory effects. It illustrates key examples of the roles played by neuromodulation in sensory processing, neuromuscular transmission, generation of motor behaviors, and learning. The book also underscores the importance of information processing by the nervous system in future studies. For neurobiology students and researchers, the book summarizes a vast amount of research in the context of how these cellular mechanisms are used in systems of neurons. By spanning the levels of analysis from sub- cellular mechanisms through cellular properties and neuronal systems to behavior, the book provides a framework for understanding this rapidly advancing field. The language is accessible to anyone with a basic understanding of neurobiology, but covers topics in depth for those familiar with neuromodulation and information processing.

Metamodulation of the biogenic amines: second-order modulation by steroid hormones and amine cocktails.

KA Mesce — 2008-06-28T06:57:07-00:00

Brain, behavior and evolution, Vol. 60, No. 6. (2002), pp. 339-349.

An evolutionarily conserved feature of neural systems is that they can be modified by neuromodulators. These modulatory chemical signals include the biogenic amines, octopamine (OA), serotonin (5-HT) and dopamine (DA). Such modulation effectively broadens the operational range in which specific neural circuits can function adaptively. This report discusses how these amines are themselves modulated; for example, by the steroid hormone 20-hydroxyecdysone (20-E) or by the addition of a second biogenic amine. Such second-order neuromodulation, termed metamodulation, is discussed in the context of two well-studied invertebrate systems: the tobacco hornworm moth Manduca sexta, a model of neurodevelopment and plasticity, and the medicinal leech Hirudo medicinalis, a long-favored preparation used to study neural circuits at the level of identified neurons. A portion of this article reviews our previous research of M. sexta that shows that the 'preadult' rise in 20-E is both necessary and sufficient for the increased levels of octopamine observed in the adult. Such elevated levels likely play an important role in the production and modulation of adult behaviors. The somatic growth of median octopaminergic neurons and the late expression of OA-immunoreactivity by novel lateral neurons are also demonstrated to be dependent on 20-E. New immunocytochemical results of stained dopaminergic neurons in the larval and adult moth brain are provided as well, and the potential influence of 20-E on the developmental expression of this neuromodulator is presented. Turning attention to the leech, data indicate that the actions of OA are dramatically altered when 5-HT is combined with OA in the bath surrounding the isolated nervous system. Although either OA or 5-HT alone induces fictive swimming behavior, a cocktail of these two amines strongly inhibits the generation of swimming. Subsequent removal of such a mixture induces nearly continuous swimming and constitutes the best swim-inducing stimulus encountered to date. To understand better how these nonadditive effects are achieved, new results are discussed that indicate that the leech brain is the target of metamodulation by the two amines. Both the arthropod and annelid systems presented here highlight the multiple levels of metamodulation that can exist in nervous systems, and the diverse ways that a modulator's actions can become altered over short or long time periods.

A role for octopamine in honey bee division of labor.

DJ Schulz — 2008-06-28T06:48:42-00:00

Brain, behavior and evolution, Vol. 60, No. 6. (2002), pp. 350-359.

Efficient division of labor is one of the main reasons for the success of the social insects. In honey bees the division of labor is principally achieved by workers changing tasks as they age. Typically, young adult bees perform a series of tasks within the colony before ultimately making the transition to foraging outside the hive for resources. This lifelong behavioral development is a well-characterized example of naturally occurring behavioral plasticity, but its neural bases are not well understood. Two techniques were used to assess the role of biogenic amines in the transition from in-hive work to foraging, which is the most dramatic and obvious transition in honey bee behavioral development. First, associations between amines and tasks were determined by measuring the levels of amines in dissected regions of individual bee brains using HPLC analysis. Second, colonies were orally treated with biogenic amines and effects on the onset of foraging were observed. Octopamine concentration in the antennal lobes of the bee brain was most reliably associated with task: high in foragers and low in nurses regardless of age. In contrast, octopamine in the mushroom bodies, a neighboring neuropil, was associated with age and not behavior, indicating independent modulation of octopamine in these two brain regions. Treating colonies with octopamine resulted in an earlier onset of foraging in young bees. In addition, octopamine levels were not elevated by non-foraging flight, but were already high on return from the first successful foraging trip and subsequently remained high, showing no further change with foraging experience. This observation suggests that octopamine becomes elevated in the antennal lobes in anticipation of foraging and is involved in the release and maintenance of the foraging state. Foraging itself, however, does not modulate octopamine levels. Behaviorally related changes in octopamine are modulated by juvenile hormone, which has also been implicated in the control of honey bee division of labor. Treatment with the juvenile hormone analog methoprene elevated octopamine and octopamine treatment 'rescued' the delay in behavioral development caused by experimentally depleting juvenile hormone in bees. Although the pathways linking juvenile hormone and octopamine are presently unknown, it is clear that octopamine acts 'downstream' of juvenile hormone to influence behavior and that juvenile hormone modulates brain octopamine levels. A working hypothesis is that octopamine acts as an activator of foraging by modulating responsiveness to foraging-related stimuli. This is supported by the finding that octopamine treatment increased the response of bees to brood pheromone, a stimulator of foraging activity. Establishing a role for octopamine in honey bee behavioral development is a first step in understanding the neural bases of this example of naturally occurring, socially mediated, behavioral plasticity. The next level of analysis will be to determine precisely where and how octopamine acts in the nervous system to coordinate this complex social behavior.

Modulation of neural networks for behavior.

RM Harris-Warrick — 2008-06-28T06:45:53-00:00

Annual review of neuroscience, Vol. 14 (1991), pp. 39-57.

Comparative psychoneuroimmunology: evidence from the insects.

SA Adamo — 2008-06-28T06:26:33-00:00

Behavioral and cognitive neuroscience reviews, Vol. 5, No. 3. (September 2006), pp. 128-140.

Interactions between immune systems, nervous systems, and behavior are well established in vertebrates. A comparative examination of these interactions in other animals will help us understand their evolution and present adaptive functions. Insects show immune-behavioral interactions similar to those seen in vertebrates, suggesting that many of them may have a highly conserved function. Activation of an immune response in insects results in illness-induced anorexia, behavioral fever, changes in reproductive behavior, and decreased learning ability in a broad range of species. Flight-or-fight behaviors result in a decline in disease resistance. In insects, illness-induced anorexia may enhance immunity. Stress-induced immunosuppression is probably due to physiological conflicts between the immune response and those of other physiological processes. Because insects occupy a wide range of ecological niches, they will be useful in examining how some immune-behavioral interactions are sculpted by an animal's behavioral ecology.

Parasitic manipulation: where are we and where should we go?

Frédéric Thomas — 2008-06-28T06:25:10-00:00

Behavioural Processes, Vol. 68, No. 3. (31 March 2005), pp. 185-199.

Modulating the modulators: parasites, neuromodulators and host behavioral change.

SA Adamo — 2008-06-28T06:23:12-00:00

Brain, behavior and evolution, Vol. 60, No. 6. (2002), pp. 370-377.

Neuromodulators can resculpt neural circuits, giving an animal the behavioral flexibility it needs to survive in a complex changing world. This ability, however, provides parasites with a potential mechanism for manipulating host behavior. This paper reviews three invertebrate host-parasite systems to examine whether parasites can change host behavior by secreting neuromodulators. The parasitic wasp, Cotesia congregata, suppresses host feeding partly by inducing the host (Manduca sexta) to increase the octopamine concentration in its hemolymph. The increased octopamine concentration disrupts the motor pattern produced by the frontal ganglion, preventing the ingestion of food. Polymorphus paradoxus (Acanthocephalan) alters the escape behavior of its host, Gammarus lacustris (Crustacea), possibly through an effect on the host's serotonergic system. The trematode Trichobilharzia ocellata inhibits egg-laying in its snail host (Lymnaea stagnalis), partly by inducing the host to secrete schistosomin. Schistosomin decreases electrical excitability of the caudodorsal cells. The parasite also alters gene expression for some neuromodulators within the host's central nervous system. In at least two of these three examples, it appears that the host, not the parasite, produces the neuromodulators that alter host behavior. Producing physiologically potent concentrations of neuromodulators may be energetically expensive for many parasites. Parasites may exploit indirect less energetically expensive methods of altering host behavior. For example, parasites may induce the host's immune system to produce the appropriate neuromodulators. In many parasites, the ability to manipulate host behavior may have evolved from adaptations designed to circumvent the host's immune system. Immune-neural-behavioral connections may be pre-adapted for parasitic manipulation.

Spike Timing-Dependent Serotonergic Neuromodulation of Synaptic Strength Intrinsic to a Central Pattern Generator Circuit

Akira Sakurai — 2008-06-28T06:19:04-00:00

J. Neurosci., Vol. 23, No. 34. (26 November 2003), pp. 10745-10755.

Neuromodulation is often thought to have a static, gain-setting function in neural circuits. Here we report a counter example: the neuromodulatory effect of a serotonergic neuron is dependent on the interval between its spikes and those of the neuron being modulated. The serotonergic dorsal swim interneurons (DSIs) are members of the escape swim central pattern generator (CPG) in the mollusk Tritonia diomedea. DSI spike trains heterosynaptically enhanced synaptic potentials evoked by another CPG neuron, ventral swim interneuron B (VSI-B), when VSI-B action potentials occurred within 10 sec of a DSI spike train; however, if VSI-B was stimulated 20-120 sec after DSI, then the amplitude of VSI-B synaptic potentials decreased. Consistent with this, VSI-B-evoked synaptic currents exhibited a temporally biphasic and bidirectional change in amplitude after DSI stimulation. Both the DSI-evoked enhancement and decrement were occluded by serotonin and blocked by the serotonin receptor antagonist methysergide, suggesting that both phases are mediated by serotonin. In most preparations, however, bath-applied serotonin caused only a sustained enhancement of VSI-B synaptic strength. The heterosynaptic modulation interacted with short-term homosynaptic plasticity: DSI-evoked depression was offset by VSI-B homosynaptic facilitation. This caused a complicated temporal pattern of neuromodulation when DSI and VSI-B were stimulated to fire in alternating bursts to mimic the natural motor pattern: DSI strongly enhanced summated VSI-B synaptic potentials and suppressed single synaptic potentials after the cessation of the artificial motor pattern. Thus, spike timing-dependent serotonergic neuromodulatory actions can impart temporal information that may be relevant to the operation of the CPG.

Frequency of Dopamine Concentration Transients Increases in Dorsal and Ventral Striatum of Male Rats during Introduction of Conspecifics

Donita Robinson — 2008-06-27T05:38:33-00:00

J. Neurosci., Vol. 22, No. 23. (1 December 2002), pp. 10477-10486.

Transient, elevated concentrations of extracellular dopamine were characterized in the dorsal and ventral striatum of male rats during solitude, brief interaction with a conspecific, and copulation. Conspecific rats were systematically presented to male rats and allowed to interact for 30 sec; the males were kept in solitude between each presentation. During these episodes, 125 dopamine concentration transients from 17 rats were detected with fast-scan cyclic voltammetry at carbon-fiber microelectrodes (peak amplitude, 210 +/- 10 nM; duration, 530 +/- 20 msec). The frequency of dopamine transients increased sixfold during conspecific episodes compared with solitude. However, the phasic dopamine activity habituated on the second presentation of the conspecifics. When males were allowed to copulate with receptive females, additional dopamine transients were observed at frequencies ~20% of those during the previous interaction episodes. A subset of these transients immediately preceded intromission. Overall, phasic dopamine activity appeared to be associated with input from multiple sensory modalities and was followed by a variety of approach and appetitive behaviors, consistent with electrophysiological observations of dopaminergic neuron burst-firing. In summary, (1) dopamine concentration transients occur in awake rats during solitude, in the absence of overt external cues; (2) dopamine transients are significantly more frequent in the presence of a conspecific, although this effect habituates; and (3) dopamine transients are less frequent during copulation than during brief conspecific episodes. These results establish for the first time that transient dopamine fluctuations occur throughout the dorsal and ventral striatum and demonstrate that they are more frequent with salient stimuli that elicit a response behavior.

Firing modes of midbrain dopamine cells in the freely moving rat

BI Hyland — 2008-06-27T05:34:19-00:00

Neuroscience, Vol. 114, No. 2. (1 October 2002), pp. 475-492.

There is a large body of data on the firing properties of dopamine cells in anaesthetised rats or rat brain slices. However, the extent to which these data relate to more natural conditions is uncertain, as there is little quantitative information available on the firing properties of these cells in freely moving rats. We examined this by recording from the midbrain dopamine cell fields using chronically implanted microwire electrodes. (1) In most cases, slowly firing cells with broad action potentials were profoundly inhibited by the dopamine agonist apomorphine, consistent with previously accepted criteria. However, a small group of cells was found that were difficult to classify because of ambiguous combinations of properties. (2) Presumed dopamine cells could be divided into low and high bursting (>40% of their spikes in bursts) groups, with the majority having low bursting rates. The distribution of burst incidence was similar to that previously reported with chloral hydrate anaesthesia, but the average intraburst frequency was higher in the conscious animal at rest and was higher again in bursts triggered by salient stimuli. (3) There was no evidence for spike frequency adaptation within bursts on average, consistent with the hypothesis that afterhyperpolarisation currents may be disabled during behaviourally induced bursting. (4) Presumed dopamine cells responded to reward-related stimuli with increased bursting rates and significantly higher intraburst frequencies compared to bursts emitted outside task context, indicating that modulation of afferent activity might not only trigger bursting, but may also regulate burst intensity. (5) In addition to the irregular single spike and bursting modes we found that extremely regular (clock-like) firing, previously only described for dopamine cells in reduced preparations, can also be expressed in the freely moving animal. (6) Cross-correlation analysis of activity recorded from simultaneously recorded neurones revealed coordinated activity in a quarter of dopamine cell pairs consistent with at least [`]functional' connectivity. On the other hand, most dopamine cell pairs showed no correlation, leaving open the possibility of functional sub-groupings within the dopamine cell fields. Taken together, the data suggest that the basic firing modes described for dopamine cells in reduced or anaesthetised preparations do reflect natural patterns of activity for these neurones, but also that the details of this activity are dependent upon modulation of afferent inputs by behavioural stimuli.

Feeding behavior of Aplysia: A model system for comparing cellular mechanisms of classical and operant conditioning

Douglas Baxter — 2008-06-24T06:11:19-00:00

Learn. Mem., Vol. 13, No. 6. (1 November 2006), pp. 669-680.

Feeding behavior of Aplysia provides an excellent model system for analyzing and comparing mechanisms underlying appetitive classical conditioning and reward operant conditioning. Behavioral protocols have been developed for both forms of associative learning, both of which increase the occurrence of biting following training. Because the neural circuitry that mediates the behavior is well characterized and amenable to detailed cellular analyses, substantial progress has been made toward a comparative analysis of the cellular mechanisms underlying these two forms of associative learning. Both forms of associative learning use the same reinforcement pathway (the esophageal nerve, En) and the same reinforcement transmitter (dopamine, DA). In addition, at least one cellular locus of plasticity (cell B51) is modified by both forms of associative learning. However, the two forms of associative learning have opposite effects on B51. Classical conditioning decreases the excitability of B51, whereas operant conditioning increases the excitability of B51. Thus, the approach of using two forms of associative learning to modify a single behavior, which is mediated by an analytically tractable neural circuit, is revealing similarities and differences in the mechanisms that underlie classical and operant conditioning. 10.1101/lm.339206

Dopamine-Mediated Volume Transmission in Midbrain Is Regulated by Distinct Extracellular Geometry and Uptake

Stephanie Cragg — 2008-06-23T07:45:07-00:00

J Neurophysiol, Vol. 85, No. 4. (1 April 2001), pp. 1761-1771.

Cragg, Stephanie J., Charles Nicholson, June Kume-Kick, Lian Tao, and Margaret E. Rice. Dopamine-Mediated Volume Transmission in Midbrain Is Regulated by Distinct Extracellular Geometry and Uptake. J. Neurophysiol. 85: 1761-1771, 2001. Somatodendritic release of dopamine (DA) in midbrain is, at least in part, nonsynaptic; moreover, midbrain DA receptors are predominantly extrasynaptic. Thus somatodendritic DA mediates volume transmission, with an efficacy regulated by the diffusion and uptake characteristics of the local extracellular microenvironment. Here, we quantitatively evaluated diffusion and uptake in substantia nigra pars compacta (SNc) and reticulata (SNr), ventral tegmental area (VTA), and cerebral cortex in guinea pig brain slices. The geometric parameters that govern diffusion, extracellular volume fraction ([alpha]) and tortuosity ([lambda]), together with linear uptake (k'), were determined for tetramethylammonium (TMA+), and for DA, using point-source diffusion combined with ion-selective and carbon-fiber microelectrodes. TMA+-diffusion measurements revealed a large [alpha] of 30% in SNc, SNr, and VTA, which was significantly higher than the 22% in cortex. Values for [lambda] and k' for TMA+ were similar among regions. Point-source DA-diffusion curves fitted theory well with linear uptake, with significantly higher values of k' for DA in SNc and VTA (0.08-0.09 s[-]1) than in SNr (0.006 s[-]1), where DA processes are sparser. Inhibition of DA uptake by GBR-12909 caused a greater decrease in k' in SNc than in VTA. In addition, DA uptake was slightly decreased by the norepinephrine transport inhibitor, desipramine in both regions, although this was statistically significant only in VTA. We used these data to model the radius of influence of DA in midbrain. Simulated release from a 20-vesicle point source produced DA concentrations sufficient for receptor activation up to 20 microm away with a DA half-life at this distance of several hundred milliseconds. Most importantly, this model showed that diffusion rather than uptake was the most important determinant of DA time course in midbrain, which contrasts strikingly with the striatum where uptake dominates. The issues considered here, while specific for DA in midbrain, illustrate fundamental biophysical properties relevant for all extracellular communication.

Discrimination and dialogue in the immune system

Irun Cohen — 2008-06-22T13:00:24-00:00

Seminars in Immunology, Vol. 12, No. 3. (June 2000), pp. 215-219.

This paper presents reasons for concluding that the immune system maintains the individual body throughout the vicissitudes of life without the need to make an absolute distinction between self and nonself. Self-maintenance and defence against parasites both require measured inflammation, and the immune system, in both its innate and adaptive arms, regulates inflammation. The intensity, dynamics and orchestration of inflammation emerge from an ongoing dialogue.

Autoimmunity can benefit self-maintenance

Michal Schwartz — 2008-06-22T13:00:15-00:00

Immunology Today, Vol. 21, No. 6. (1 June 2000), pp. 265-268.

Autoimmunity is usually considered only as a cause of disease; nevertheless, human T-cell repertoires are filled naturally with autoimmune lymphocytes. Here, we review evidence that autoimmune T cells can help heal damaged tissues, indicating that natural autoimmunity could also be a cause of health.

Tending Adam's Garden : Evolving the Cognitive Immune Self

Irun Cohen — 2006-11-28T02:58:22-00:00

(10 August 2004)

Tending Adam's Garden describes and explains the way in which our immune system works from a novel perspective. The book uses metaphors and examples to bring the immune system to life and explores the fundamental miracle of nature. Written in plain language for a broad audience, this book encompasses much more than just immunology, exploring more fundamental matters such as causality, information, energy, evolution, cognition and individuality, as well as the strategy of the immune system and its role in health and disease. * Provides a unique perspective on the immune system from one of the keenest scientific and philosophical brains in the world * Uses metaphors and case histories to explore themes in an accessible manner * Written in plain language requiring no specialized vocabulary or specific scientific background in the subject

Biomarkers, self-antigens and the immunological homunculus

Irun Cohen — 2008-06-22T12:49:33-00:00

Journal of Autoimmunity, Vol. 29, No. 4. (December 2007), pp. 246-249.

The notion of the immunological homunculus arose from the observations (1) that the healthy adaptive immune system is inclined to respond (T cell reactivity and autoantibodies) to particular sets of body molecules (self-antigens) and (2) that autoimmune diseases are characterized by sets of autoimmune reactivity to some of the very same self-antigens recognized by healthy subjects - with an obvious difference in outcome. I termed this natural autoimmune structuring of the immune system, the immunological homunculus - the immune system's representation of the body. What might be the selective advantage of an immune system expressing patterns of built-in autoimmunity to particular sets of self-molecules? To better characterize the homunculus, we have used informatic tools to study patterns of antibodies to many hundreds of self-molecules arrayed on glass slides - an antigen chip of our design. Results using the antigen chip suggest that the particular self-reactivities comprising the homunculus could serve as a set of biomarkers that help the immune system initiate and regulate the inflammatory processes that maintain the body.

DAncing past the DAT at a DA synapse

Stephanie Cragg — 2008-06-21T07:01:37-00:00

Trends in Neurosciences, Vol. 27, No. 5. (May 2004), pp. 270-277.

Spillover of dopamine (DA) from a release site into the extrasynaptic space is widely acknowledged. Indeed, spillover is necessary for signalling by DA because its receptors are predominantly extrasynaptic. Dopamine transporters (DATs) are often considered to participate in this process by [`]gating' spillover. This article reviews the competition between DATs and diffusion in sculpting extracellular DA transients after quantal release, using a model based on data from the literature. Its conclusions challenge the view that DATs limit synaptic DA concentration and gate initial spillover from a release site; this is the work of diffusion. Rather, the greatest influence of DATs, or of their inhibition, is on the sphere of influence and lifetime of DA beyond a release site and, thus, on net extracellular concentration.

Prolonged and Extrasynaptic Excitatory Action of Dopamine Mediated by D1 Receptors in the Rat Striatum In Vivo

Francois Gonon — 2007-06-11T02:29:15-00:00

J. Neurosci., Vol. 17, No. 15. (1 August 1997), pp. 5972-5978.

Dopamine release is heterogeneous within microenvironments of the rat nucleus accumbens

Wightman — 2007-10-08T14:55:17-00:00

European Journal of Neuroscience, Vol. 26, No. 7. (October 2007), pp. 2046-2054.

Spiking neurons, dopamine, and plasticity: Timing is everything, but concentration also matters

Jean-Philippe Thivierge — 2008-06-21T05:32:54-00:00

Synapse, Vol. 61, No. 6. (2007), pp. 375-390.

While both dopamine (DA) fluctuations and spike-timing-dependent plasticity (STDP) are known to influence long-term corticostriatal plasticity, little attention has been devoted to the interaction between these two fundamental mechanisms. Here, a theoretical framework is proposed to account for experimental results specifying the role of presynaptic activation, postsynaptic activation, and concentrations of extracellular DA in synaptic plasticity. Our starting point was an explicitly-implemented multiplicative rule linking STDP to Michaelis-Menton equations that models the dynamics of extracellular DA fluctuations. This rule captures a wide range of results on conditions leading to long-term potentiation and depression in simulations that manipulate the frequency of induced corticostriatal stimulation and DA release. A well-documented biphasic function relating DA concentrations to synaptic plasticity emerges naturally from simulations involving a multiplicative rule linking DA and neural activity. This biphasic function is found consistently across different neural coding schemes employed (voltage-based vs. spike-based models). By comparison, an additive rule fails to capture these results. The proposed framework is the first to generate testable predictions on the dual influence of DA concentrations and STDP on long-term plasticity, suggesting a way in which the biphasic influence of DA concentrations can modulate the direction and magnitude of change induced by STDP, and raising the possibility that DA concentrations may inverse the LTP/LTD components of the STDP rule. Synapse 61:375-390, 2007. © 2007 Wiley-Liss, Inc.

Real-time decoding of dopamine concentration changes in the caudate-putamen during tonic and phasic firing

Jill Venton — 2008-06-21T05:27:38-00:00

Journal of Neurochemistry, Vol. 87, No. 5. (2003), pp. 1284-1295.

Abstract The fundamental process that underlies volume transmission in the brain is the extracellular diffusion of neurotransmitters from release sites to distal target cells. Dopaminergic neurons display a range of activity states, from low-frequency tonic firing to bursts of high-frequency action potentials (phasic firing). However, it is not clear how this activity affects volume transmission on a subsecond time scale. To evaluate this, we developed a finite-difference model that predicts the lifetime and diffusion of dopamine in brain tissue. We first used this model to decode in vivo amperometric measurements of electrically evoked dopamine, and obtained rate constants for release and uptake as well as the extent of diffusion. Accurate predictions were made under a variety of conditions including different regions, different stimulation parameters and with uptake inhibited. Second, we used the decoded rate constants to predict how heterogeneity of dopamine release and uptake sites would affect dopamine concentration fluctuations during different activity states in the absence of an electrode. These simulations show that synchronous phasic firing can produce spatially and temporally heterogeneous concentration profiles whereas asynchronous tonic firing elicits uniform, steady-state dopamine concentrations.

Dopaminergic signaling in dendritic spines

Wei-Dong Yao — 2008-03-27T09:02:10-00:00

Biochemical Pharmacology, Vol. In Press, Corrected Proof

Dopamine regulates movement, motivation, reward, and learning and is implicated in numerous neuropsychiatric and neurological disorders. The action of dopamine is mediated by a family of seven-transmembrane G protein-coupled receptors encoded by at least five dopamine receptor genes (D1, D2, D3, D4, and D5), some of which are major molecular targets for diverse neuropsychiatric medications. Dopamine receptors are present throughout the soma and dendrites of the neuron, but accumulating ultrastructural and biochemical evidence indicates that they are concentrated in dendritic spines, where most of the glutamatergic synapses are established. By modulating local channels, receptors, and signaling modules in spines, this unique population of postsynaptic receptors is strategically positioned to control the excitability and synaptic properties of spines and mediate both the tonic and phasic aspects of dopaminergic signaling with remarkable precision and versatility. The molecular mechanisms that underlie the trafficking, targeting, anchorage, and signaling of dopamine receptors in spines are, however, largely unknown. The present commentary focuses on this important subpopulation of postsynaptic dopamine receptors with emphases on recent molecular, biochemical, pharmacological, ultrastructural, and physiological studies that provide new insights about their regulatory mechanisms and unique roles in dopamine signaling.

Allosteric changes of the NMDA receptor trap diffusible dopamine 1 receptors in spines

Lena Scott — 2008-06-20T05:57:11-00:00

Proceedings of the National Academy of Sciences, Vol. 103, No. 3. (17 January 2006), pp. 762-767.

The dopaminergic and glutamatergic systems interact to initiate and organize normal behavior, a communication that may be perturbed in many neuropsychiatric diseases, including schizophrenia. We show here that NMDA, by allosterically modifying NMDA receptors, can act as a scaffold to recruit laterally diffusing dopamine D1 receptors (D1R) to neuronal spines. Using organotypic culture from rat striatum transfected with D1R fused to a fluorescent protein, we show that the majority of dendritic D1R are in lateral diffusion and that their mobility is confined by interaction with NMDA receptors. Exposure to NMDA reduces the diffusion coefficient for D1R and causes an increase in the number of D1R-positive spines. Unexpectedly, the action of NMDA in potentiating D1R recruitment was independent of calcium flow via the NMDA receptor channel. Thus, a highly energy-efficient, diffusion-trap mechanism can account for intraneuronal interaction between the glutamatergic and dopaminergic systems and for regulation of the number of D1R-positive spines. This diffusion trap system represents a molecular mechanism for brain plasticity and offers a promising target for development of antipsychotic therapy. 10.1073/pnas.0505557103

Dendritic excitability and synaptic plasticity.

PJ Sjöström — 2008-06-15T09:17:23-00:00

Physiological reviews, Vol. 88, No. 2. (April 2008), pp. 769-840.

Most synaptic inputs are made onto the dendritic tree. Recent work has shown that dendrites play an active role in transforming synaptic input into neuronal output and in defining the relationships between active synapses. In this review, we discuss how these dendritic properties influence the rules governing the induction of synaptic plasticity. We argue that the location of synapses in the dendritic tree, and the type of dendritic excitability associated with each synapse, play decisive roles in determining the plastic properties of that synapse. Furthermore, since the electrical properties of the dendritic tree are not static, but can be altered by neuromodulators and by synaptic activity itself, we discuss how learning rules may be dynamically shaped by tuning dendritic function. We conclude by describing how this reciprocal relationship between plasticity of dendritic excitability and synaptic plasticity has changed our view of information processing and memory storage in neuronal networks.

Dopamine Receptor Activation Is Required for Corticostriatal Spike-Timing-Dependent Plasticity

Verena Pawlak — 2008-03-06T14:16:09-00:00

J. Neurosci., Vol. 28, No. 10. (5 March 2008), pp. 2435-2446.

Single action potentials (APs) backpropagate into the higher-order dendrites of striatal spiny projection neurons during cortically driven "up" states. The timing of these backpropagating APs relative to the arriving corticostriatal excitatory inputs determines changes in dendritic calcium concentration. The question arises to whether this spike-timing relative to cortical excitatory inputs can also induce synaptic plasticity at corticostriatal synapses. Here we show that timing of single postsynaptic APs relative to the cortically evoked EPSP determines both the direction and the strength of synaptic plasticity in spiny projection neurons. Single APs occurring 30 ms before the cortically evoked EPSP induced long-term depression (LTD), whereas APs occurring 10 ms after the EPSP induced long-term potentiation (LTP). The amount of plasticity decreased as the time between the APs and EPSPs was increased, with the resulting spike-timing window being broader for LTD than for LTP. In addition, we show that dopamine receptor activation is required for this spike-timing-dependent plasticity (STDP). Blocking dopamine D1/D5 receptors prevented both LTD and LTP induction. In contrast, blocking dopamine D2 receptors delayed, but did not prevent, LTD and sped induction of LTP. We conclude (1) that, in combination with cortical inputs, single APs evoked in spiny projection neurons can induce both LTP and LTD of the corticostriatal pathway; (2) that the strength and direction of these synaptic changes depend deterministically on the AP timing relative to the arriving cortical inputs; (3) that, whereas dopamine D2 receptor activation modulates the initial phase of striatal STDP, dopamine D1/D5 receptor activation is critically required for striatal STDP. Thus, the timing of APs relative to cortical inputs alone is not enough to induce corticostriatal plasticity, implying that ongoing activity does not affect synaptic strength unless dopamine receptors are activated. 10.1523/JNEUROSCI.4402-07.2008

Reinforcement Learning With Modulated Spike Timing Dependent Synaptic Plasticity

Michael Farries — 2008-06-16T23:51:03-00:00

J Neurophysiol, Vol. 98, No. 6. (1 December 2007), pp. 3648-3665.

Spike timing-dependent synaptic plasticity (STDP) has emerged as the preferred framework linking patterns of pre- and postsynaptic activity to changes in synaptic strength. Although synaptic plasticity is widely believed to be a major component of learning, it is unclear how STDP itself could serve as a mechanism for general purpose learning. On the other hand, algorithms for reinforcement learning work on a wide variety of problems, but lack an experimentally established neural implementation. Here, we combine these paradigms in a novel model in which a modified version of STDP achieves reinforcement learning. We build this model in stages, identifying a minimal set of conditions needed to make it work. Using a performance-modulated modification of STDP in a two-layer feedforward network, we can train output neurons to generate arbitrarily selected spike trains or population responses. Furthermore, a given network can learn distinct responses to several different input patterns. We also describe in detail how this model might be implemented biologically. Thus our model offers a novel and biologically plausible implementation of reinforcement learning that is capable of training a neural population to produce a very wide range of possible mappings between synaptic input and spiking output. 10.1152/jn.00364.2007

Spine Ca2+ Signaling in Spike-Timing-Dependent Plasticity

Thomas Nevian — 2008-06-17T15:29:55-00:00

J. Neurosci., Vol. 26, No. 43. (25 October 2006), pp. 11001-11013.

Calcium is a second messenger, which can trigger the modification of synaptic efficacy. We investigated the question of whether a differential rise in postsynaptic Ca2+ ([Ca2+]i) alone is sufficient to account for the induction of long-term potentiation (LTP) and long-term depression (LTD) of EPSPs in the basal dendrites of layer 2/3 pyramidal neurons of the somatosensory cortex. Volume-averaged [Ca2+]i transients were measured in spines of the basal dendritic arbor for spike-timing-dependent plasticity induction protocols. The rise in [Ca2+]i was uncorrelated to the direction of the change in synaptic efficacy, because several pairing protocols evoked similar spine [Ca2+]i transients but resulted in either LTP or LTD. The sequence dependence of near-coincident presynaptic and postsynaptic activity on the direction of changes in synaptic strength suggested that LTP and LTD were induced by two processes, which were controlled separately by postsynaptic [Ca2+]i levels. Activation of voltage-dependent Ca2+ channels before metabotropic glutamate receptors (mGluRs) resulted in the phospholipase C-dependent (PLC-dependent) synthesis of endocannabinoids, which acted as a retrograde messenger to induce LTD. LTP required a large [Ca2+]i transient evoked by NMDA receptor activation. Blocking mGluRs abolished the induction of LTD and uncovered the Ca2+-dependent induction of LTP. We conclude that the volume-averaged peak elevation of [Ca2+]i in spines of layer 2/3 pyramids determines the magnitude of long-term changes in synaptic efficacy. The direction of the change is controlled, however, via a mGluR-coupled signaling cascade. mGluRs act in conjunction with PLC as sequence-sensitive coincidence detectors when postsynaptic precede presynaptic action potentials to induce LTD. Thus presumably two different Ca2+ sensors in spines control the induction of spike-timing-dependent synaptic plasticity. 10.1523/JNEUROSCI.1749-06.2006

DARPP-32 is a robust integrator of dopamine and glutamate signals.

E Fernandez — 2007-10-15T15:29:02-00:00

PLoS Comput Biol, Vol. 2, No. 12. (22 December 2006)

Integration of neurotransmitter and neuromodulator signals in the striatum plays a central role in the functions and dysfunctions of the basal ganglia. DARPP-32 is a key actor of this integration in the GABAergic medium-size spiny neurons, in particular in response to dopamine and glutamate. When phosphorylated by cAMP-dependent protein kinase (PKA), DARPP-32 inhibits protein phosphatase-1 (PP1), whereas when phosphorylated by cyclin-dependent kinase 5 (CDK5) it inhibits PKA. DARPP-32 is also regulated by casein kinases and by several protein phosphatases. These complex and intricate regulations make simple predictions of DARPP-32 dynamic behaviour virtually impossible. We used detailed quantitative modelling of the regulation of DARPP-32 phosphorylation to improve our understanding of its function. The models included all the combinations of the three best-characterized phosphorylation sites of DARPP-32, their regulation by kinases and phosphatases, and the regulation of those enzymes by cAMP and Ca(2+) signals. Dynamic simulations allowed us to observe the temporal relationships between cAMP and Ca(2+) signals. We confirmed that the proposed regulation of protein phosphatase-2A (PP2A) by calcium can account for the observed decrease of Threonine 75 phosphorylation upon glutamate receptor activation. DARPP-32 is not simply a switch between PP1-inhibiting and PKA-inhibiting states. Sensitivity analysis showed that CDK5 activity is a major regulator of the response, as previously suggested. Conversely, the strength of the regulation of PP2A by PKA or by calcium had little effect on the PP1-inhibiting function of DARPP-32 in these conditions. The simulations showed that DARPP-32 is not only a robust signal integrator, but that its response also depends on the delay between cAMP and calcium signals affecting the response to the latter. This integration did not depend on the concentration of DARPP-32, while the absolute effect on PP1 varied linearly. In silico mutants showed that Ser137 phosphorylation affects the influence of the delay between dopamine and glutamate, and that constitutive phosphorylation in Ser137 transforms DARPP-32 in a quasi-irreversible switch. This work is a first attempt to better understand the complex interactions between cAMP and Ca(2+) regulation of DARPP-32. Progressive inclusion of additional components should lead to a realistic model of signalling networks underlying the function of striatal neurons.

Immunology for physicists

Alan Perelson — 2008-05-29T09:05:42-00:00

Reviews of Modern Physics, Vol. 69, No. 4. (1 October 1997), 1219.

Modelling the Hypothalamic Control of Growth Hormone Secretion

DJ Macgregor — 2008-05-22T15:22:46-00:00

Journal of Neuroendocrinology, Vol. 17, No. 12. (2005), pp. 788-803.

Abstract Here, we construct a mathematical model of the hypothalamic systems that control the secretion of growth hormone (GH). The work extends a recent model of the pituitary GH system, adding representations of the hypothalamic GH-releasing hormone (GHRH) and somatostatin neurones, each modelled as a single synchronised unit. An unpatterned stochastic input drives the GHRH neurones generating pulses of GHRH release that trigger GH pulses. Delayed feedback from GH results in increased somatostatin release, which inhibits both GH secretion and GHRH release, producing an overall pattern of 3-h pulses of GH secretion that is very similar to the secretory profile observed in male rats. Rather than directly stimulating somatostatin release, GH feedback triggers a priming effect, increasing releasable stores of somatostatin. Varying this priming effect to reduce the effect of GH can reproduce the less pulsatile form of GH release observed in the female rat. The model behaviour is tested by comparison with experimental observations with a range of different experimental protocols involving GHRH injections and somatostatin and GH infusion.

Permaculture One: A Perennial Agricultural System for Human Settlements

Mollison — 2008-01-07T19:52:46-00:00

One-straw Revolution: Introduction to Natural Farming

Masanobu Fukuoka — 2008-05-21T10:26:36-00:00

Introducing Biological Rhythms: A Primer on the Temporal Organization of Life, with Implications for Health, Society, Reproduction, and the Natural Environment

Willard Koukkari — 2008-05-20T13:26:49-00:00

_Introducing Biological Rhythms_ is a primer that serves to introduce individuals to the area of biological rhythms. It describes the major characteristics and discusses the implications and applications of these rhythms, while citing scientific results and references. Also, the primer includes essays that provide in-depth historic and other background information for those interested in more specific topics or concepts. It covers a basic cross-section of the field of chronobiology clearly enough so that it can be understood by a novice, or an undergraduate student, but that it would also be sufficiently technical and detailed for the scientist.

Visual sensory-motor gating by serotonin activation in the medial prefrontal and occipital, but not in the rhinal, cortices in rats

ME Pum — 2008-05-16T15:40:42-00:00

Neuroscience, Vol. 153, No. 2. (2 May 2008), pp. 361-372.

A behavioral reaction to sensory stimulation is a basic mechanism which is pivotal to many complex behavioral responses. In previous studies we found that visual stimulation induces a selective serotonergic and dopaminergic activation in the occipital (OccC), but not temporal (TempC) cortex in freely moving rats. In a behavioral study in rats we demonstrate now that visual stimulation (0, 8, 22, 82, 155 or 440 lux) activates behavioral activity in an intensity-dependent manner. Behavior activating visual stimulation with 82 lux, but not 22 lux or 82 dB white noise, increased extracellular serotonin (5-HT), but not dopamine (DA), in the medial prefrontal cortex (mPFC) in freely moving animals measured by in vivo microdialysis. There was no effect on 5-HT or DA in the entorhinal and perirhinal cortex. Visual stimulation with 82 lux increased extracellular 5-HT in the mPFC and OccC also in anesthetized animals, but had no effect in the TempC. Auditory stimulation reduced 5-HT in the TempC, but had no effect in the mPFC or OccC. Neither visual nor auditory stimulation had a significant effect on DA in all three cortical areas. We conclude that visual stimulation induces behavioral activation by increasing 5-HT activity in the mPFC and OccC.

The affirmation of self: a new perspective on the immune system.

J Stewart — 2008-05-16T14:23:16-00:00

Artificial life, Vol. 10, No. 3. (2004), pp. 261-276.

The fundamental concepts of autopoiesis, which emphasize the circular organization underlying both living organisms and cognition, have been criticized on the grounds that since they are conceived as a tight logical chain of definitions and implications, it is often not clear whether they are indeed a scientific theory or rather just a potential scientific vocabulary of doubtful utility to working scientists. This article presents the deployment of the concepts of autopoiesis in the field of immunology, a discipline where working biologists themselves spontaneously have long had recourse to "cognitive" metaphors: "recognition"; a "repertoire" of recognized molecular shapes; "learning" and "memory"; and, most striking of all, a "self versus non-self" distinction. It is shown that in immunology, the concepts of autopoiesis can be employed to generate clear novel hypotheses, models demonstrating these ideas, testable predictions, and novel therapeutic procedures. Epistemologically, it is shown that the self-non-self distinction, while quite real, is misleadingly named. When a real mechanism for generating this distinction is identified, it appears that the actual operational distinction is between (a) a sufficiently numerous set of initial antigens, present from the start of ontogeny, in conditions that allow for their participation in the construction of the system's organization and operation, and (b) single antigens that are first presented to the system after two successive phases of maturation. To call this a self-non-self distinction obscures the issue by presupposing what it ought to be the job of scientific investigation to explain.

The Biological Function Paradigm Applied to the Immunological Self-Non-Self Discrimination: Critique of Tauber's Phenomenological Analysis

Wilfried Allaerts — 2008-05-16T14:11:42-00:00

Journal for General Philosophy of Science, Vol. 30, No. 1. (16 January 1999), pp. 155-171.

Abstract Biological self reference idioms in brain-centered or nervous-system-centered self determination of the consious Self reveal an interesting contrast with biological self-determination by immunological self/non-self discrimination. This contrast is both biological and epistemological. In contrast to the consciousness conscious of itself, the immunological self-determination imposes a protective mechanism against self-recognition (Coutinho et al. 1984), which adds to a largely unconscious achievement of the biological Self (Popper 1977; Medawar 1959). The latter viewpoint is in contrast with the immunological Self-determination as an essentially cognitive process as expressed in the analysis of Tauber (1994). Comparison of the immune system in vertebrates and invertebrates, according to new biological insights, has contributed to a better understanding of the relative role of innate (or inherited) immunity versus immunity acquired during each individual life. Also in this respect, immunological self-achievement shows both a striking analogy and a fundamental discrepancy with the activity of the nervous system. The analysis of immunological Self/non-self discrimination versus brain-centered self-determination adds to the understanding of the function paradigm in biological self-reference idioms, especially when regarding the importance of the connectivity notion in both systems. Adopting functional explanatory schemes for understanding immunological self-non-self discrimination, as well as for the understanding of functional mapping of the brain at (conscious) activity (Friston et al. 1993; Frith et al. 1995), forwards the notion of effective/functional connectivity. Network connectivity not only is a primary question in solving the dimensionality question for immunological ‘idiotypic networks’ (Jerne 1974a, b; 1984), it may also have an important value in describing phase transitions in the development of both immune and nervous systems.

Small is Beautiful

Schumacher — 2008-05-13T14:02:51-00:00

(16 September 1993)

Guide for the Perplexed

EF Schumacher — 2008-04-30T10:42:03-00:00

(30 June 1978)

The author of the world wide best-seller, Small Is Beautiful, now tackles the subject of Man, the World, and the Meaning of Living. Schumacher writes about man's relation to the world. man has obligations -- to other men, to the earth, to progress and technology, but most importantly himself. If man can fulfill these obligations, then and only then can he enjoy a real relationship with the world, then and only then can he know the meaning of living. Schumacher says we need maps: a "map of knowledge" and a "map of living." The concern of the mapmaker--in this instance, Schumacher--is to find for everything it's proper place. Things out of place tend to get lost; they become invisible and there proper places end to be filled by other things that ought not be there at all and therefore serve to mislead. A Guide for the Perplexed teaches us to be our own map makers. This constantly surprising, always stimulating book will be welcomed by a large audience, including the many new fans who believe strongly in what Schumacher has to say.

Critique of Pure Reason (Penguin Classics)

Immanuel Kant — 2008-03-07T14:50:43-00:00

(29 January 2008)

The masterpiece of the father of modern philosophy A seminal text of modern philosophy, Immanuel Kants Critique of Pure Reason (1781) made history by bringing together two opposing schools of thought: rationalism, which grounds all our knowledge in reason, and empiricism, which traces all our knowledge to experience. Published here in a lucid reworking of Max Müllers classic translation, the Critique is a profound investigation into the nature of human reason, establishing its truth, falsities, illusions, and reality.

On the Psychology of Prediction

Daniel Kahneman — 2008-03-06T13:04:23-00:00

Psychological Review (0 1973)

In this paper, we explore the rules that determine intuitive predictions and judgments of confidence and contrast these rules to the normative principles of statistical prediction. (Author)

An opponent-process theory of motivation. I. Temporal dynamics of affect.

RL Solomon — 2008-03-06T12:24:57-00:00

Psychol Rev, Vol. 81, No. 2. (March 1974), pp. 119-145.

Cholinergic neurons and terminal fields revealed by immunohistochemistry for the vesicular acetylcholine transporter. I. Central nervous system

Schafer — 2008-03-03T14:34:45-00:00

Neuroscience, Vol. 84, No. 2. (11 February 1998), pp. 331-359.

Antibodies directed against the C-terminus of the rat vesicular acetylcholine transporter mark expression of this specifically cholinergic protein in perinuclear regions of the soma and on secretory vesicles concentrated within cholinergic nerve terminals. In the central nervous system, the vesicular acetylcholine transporter terminal fields of the major putative cholinergic pathways in cortex, hippocampus, thalamus, amygdala, olfactory cortex and interpeduncular nucleus were examined and characterized. The existence of an intrinsic cholinergic innervation of cerebral cortex was confirmed by both in situ hybridization histochemistry and immunohistochemistry for the rat vesicular acetylcholine transporter and choline acetyltransferase. Cholinergic interneurons of the olfactory tubercle and Islands of Calleja, and the major intrinsic cholinergic innervation of striatum were fully characterized at the light microscopic level with vesicular acetylcholine transporter immunohistochemistry. Cholinergic staining was much more extensive for the vesicular acetylcholine transporter than for choline acetyltransferase in all these regions, due to visualization of cholinergic nerve terminals not easily seen with immunohistochemistry for choline acetyltransferase in paraffin-embedded sections. Cholinergic innervation of the median eminence of the hypothalamus, previously observed with vesicular acetylcholine transporter immunohistochemistry, was confirmed by the presence of vesicular acetylcholine transporter immunoreactivity in extracts of median eminence by western blotting. Cholinergic projections to cerebellum, pineal gland, and to the substantia nigra were documented by vesicular acetylcholine transporter-positive punctate staining in these structures. Additional novel localizations of putative cholinergic terminals to the subependymal zone surrounding the lateral ventricles, and putative cholinergic cell bodies in the sensory mesencephalic trigeminal nucleus, a primary sensory afferent ganglion located in the brainstem, are documented here. The cholinergic phenotype of neurons of the sensory mesencephalic trigeminal nucleus was confirmed by choline acetyltransferase immunohistochemistry. A feature of cholinergic neurons of the central nervous system revealed clearly with vesicular acetylcholine transporter immunohistochemistry in paraffin-embedded sections is the termination of cholinergic neurons on cholinergic cell bodies. These are most prominent on motor neurons of the spinal cord, less prominent but present in some brainstem motor nuclei, and apparently absent from projection neurons of the telencephalon and brainstem, as well as from the preganglionic vesicular acetylcholine transporter-positive sympathetic and parasympathetic neurons visualized in the intermediolateral and intermediomedial columns of the spinal cord. In addition to the large puncta decorating motor neuronal perikarya and dendrites in the ventral horn, vesicular acetylcholine transporter-positive terminal fields are distributed in lamina X surrounding the central canal, where additional small vesicular acetylcholine transporter-positive cell bodies are located, and in the superficial layers of the dorsal horn. Components of the central cholinergic nervous system whose existence has been controversial have been confirmed, and the existence of new components documented, with immunohistochemistry for the vesicular acetylcholine transporter. Quantitative visualization of terminal fields of known cholinergic systems by staining for vesicular acetylcholine transporter will expand the possibilities for documenting changes in synaptic patency accompanying physiological and pathophysiological changes in these systems.

Why Do People Get Ill?: Exploring the Mind-body Connection

Darian Leader — 2008-02-06T18:25:08-00:00

(22 February 2007)

Psychoneuroimmunology, Two-Volume Set, Volume 1-2, Fourth Edition

Robert Ader — 2008-02-05T18:31:46-00:00

(21 September 2006)

Psychoneuroimmunology is the study of interactions among behavioral, neural and endocrine, and immunologic processes of adaptation. These two volumes provide a clearly written, extensively referenced summary of some of the behavioral, neural and endocrine regulators of immune responses and immunologically mediated disease processes and of the behavioral and neuroendocrine effects of immune system activity. Several chapters expand upon topics reviewed in earlier editions of this series; most chapters cover active areas of research that have not previously been reviewed. As illustrated in this fourth edition, interdisciplinary research continues to provide evidence that the brain and immune system represent a single, integrated system of defense. * Fully revised and updated fourth edition of the classic reference * Provides a neuroendocrine and immunologic perspective for the behavioral scientist * Provides a behavioral and neuroscience perspective for the immunologist * Helps the reader translate basic science findings into clinically relevant information * Provides the reader with the background for and foundation of integrative research and integrative medicine * Provides an encyclopedic resource for advanced undergraduates and for pre- and post-doctoral students as well as active researchers

Original Tao: Inward Training (Nei-yeh) and the Foundations of Taoist Mysticism (Translations from the Asian Classics)

HD Roth — 2008-01-29T14:59:37-00:00

(03 November 2004)

Revolutionizing received opinion of Taoism's origins in light of historic new discoveries, Harold D. Roth has uncovered China's oldest mystical text -- the original expression of Taoist philosophy -- and presents it here with a complete translation and commentary.Over the past twenty-five years, documents recovered from the tombs of China's ancient elite have sparked a revolution in scholarship about early Chinese thought, in particular the origins of Taoist philosophy and religion. In Original Tao, Harold D. Roth exhumes the seminal text of Taoism -- Inward Training (Nei-yeh) -- not from a tomb but from the pages of the Kuan Tzu, a voluminous text on politics and economics in which this mystical tract had been "buried" for centuries. Inward Training is composed of short poetic verses devoted to the practice of breath meditation, and to the insights about the nature of human beings and the form of the cosmos derived from this practice. In its poetic form and tone, the work closely resembles the Tao-te Ching; moreover, it clearly evokes Taoism's affinities to other mystical traditions, notably aspects of Hinduism and Buddhism. Roth argues that Inward Training is the foundational text of early Taoism and traces the book to the mid-fourth century B.C. (the late Warring States period in China). These verses contain the oldest surviving expressions of a method for mystical "inner cultivation," which Roth identifies as the basis for all early Taoist texts, including the Chuang Tzu and the world-renowned Tao-te Ching. With these historic discoveries, he reveals the possibility of a much deeper continuity between early "philosophical" Taoism and the later Taoist religion than scholars had previously suspected. Original Tao contains an elegant and luminous complete translation of the original text. Roth's comprehensive analysis explains what Inward Training meant to the people who wrote it, how this work came to be "entombed" within the Kuan Tzu, and why the text was largely overlooked after the early Han period.

Cutting Through Spiritual Materialism

Chogyam Trungpa — 2008-01-18T22:58:43-00:00

(22 November 2002)

In this modern spiritual classic, the Tibetan meditation master Chögyam Trungpa highlights the commonest pitfall to which every aspirant on the spiritual path falls prey: what he calls spiritual materialism. The universal tendency, he shows, is to see spirituality as a process of self-improvement—the impulse to develop and refine the ego when the ego is, by nature, essentially empty. "The problem is that ego can convert anything to its own use," he said, "even spirituality." His incisive, compassionate teachings serve to wake us up from this trick we all play on ourselves, and to offer us a far brighter reality: the true and joyous liberation that inevitably involves letting go of the self rather than working to improve it. It is a message that has resonated with students for nearly thirty years, and remains fresh as ever today. This new edition includes a foreword by Chögyam Trungpa's son and lineage holder, Sakyong Mipham.