CiteULike: awooga's library [598 articles] http://www.citeulike.org/user/awooga CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/awooga/article/2795598 <i>Brief Bioinform, Vol. 2, No. 3. (1 January 2001), pp. 245-257.</i><br /><br />Like most other fields in biology, immunology has been revolutionised by the techniques of molecular biology and the resulting explosion in available experimental data. It is argued that efforts to integrate the data to gain insight into how various subsystems in the immune system interact and function require mathematical modelling and computer simulation in close collaboration with experimentalists. This paper illustrates some of the techniques available for modelling immune systems, and highlights the issues that should be borne in mind by anyone starting down the modelling path. 10.1093/bib/2.3.245 An approach to modelling in immunology Andrew Yates Cliburn Chan Robin Callard Andrew George Jaroslav Stark doi:10.1093/bib/2.3.245 Brief Bioinform, Vol. 2, No. 3. (1 January 2001), pp. 245-257. 2008-05-13T16:32:48-00:00 Brief Bioinform 2 3 245 257 no-tag http://www.citeulike.org/user/awooga/article/2795098 <i>(16 September 1993)</i> Small is Beautiful Schumacher (16 September 1993) 2008-05-13T14:02:51-00:00 Vintage no-tag http://www.citeulike.org/user/awooga/article/2794640 <i>Science, Vol. 180, No. 4088. (1973), pp. 871-872.</i><br /><br />Injection of rabbits with acetylcholine receptor highly purified from the electric organ of Electrophorus electricus emulsified in complete Freund's adjuvant resulted in the production of precipitating antibody to acetylcholine receptor. After the second injection of antigen, the animals developed the flaccid paralysis and abnormal electromyographs characteristic of neuromuscular blockade. Treatment with the anticholinesterases edrophonium or neostigmine dramatically alleviated the paralysis and the fatigue seen in electromyography. Autoimmune Response to Acetylcholine Receptor Jim Patrick Jon Lindstrom doi:10.2307/1736585 Science, Vol. 180, No. 4088. (1973), pp. 871-872. 2008-05-13T11:30:25-00:00 Science 180 4088 871 872 American Association for the Advancement of Science acetylcholine immunology http://www.citeulike.org/user/awooga/article/1153332 <i>Annu Rev Neurosci, Vol. 23 (2000), pp. 343-391.</i><br /><br />One of the most significant developments in biology in the past half century was the emergence, in the late 1950s and early 1960s, of neuroscience as a distinct discipline. We review here factors that led to the convergence into a common discipline of the traditional fields of neurophysiology, neuroanatomy, neurochemistry, and behavior, and we emphasize the seminal roles played by David McKenzie Rioch, Francis O Schmitt, and especially Stephen W Kuffler in creating neuroscience as we now know it. The application of the techniques of molecular and cellular biology to the study of the nervous system has greatly accelerated our understanding of the mechanisms involved in neuronal signaling, neural development, and the function of the major sensory and motor systems of the brain. The elucidation of the underlying causes of most neurological and psychiatric disorders has proved to be more difficult; but striking progress is now being made in determining the genetic basis of such disorders as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and a number of ion channel and mitochondrial disorders, and a significant start has been made in identifying genetic factors in the etiology of such disorders as manic depressive illness and schizophrenia. These developments presage the emergence in the coming decades of a new nosology, certainly in neurology and perhaps also in psychiatry, based not on symptomatology but on the dysfunction of specific genes, molecules, neuronal organelles and particular neural systems. The emergence of modern neuroscience: some implications for neurology and psychiatry. WM Cowan DH Harter ER Kandel doi:10.1146/annurev.neuro.23.1.343 Annu Rev Neurosci, Vol. 23 (2000), pp. 343-391. 2007-03-11T02:14:52-00:00 Annu Rev Neurosci 0147-006X 23 343 391 no-tag http://www.citeulike.org/user/awooga/article/2789236 <i>Brain and Cognition, Vol. 49, No. 1. (June 2002), pp. 73-95.</i><br /><br />Neurotransmitters have become such an intrinsic part of our theories about brain function that many today are unaware of how difficult it was to prove their existence or the protracted dispute over the nature of synaptic transmission. The story is important not only because it is fascinating science history, but also because it exemplifies much of what is best in science and deserving to be emulated. The friendships formed among such major figures in this history as Henry Dale, Otto Loewi, Wilhelm Feldberg, Walter Cannon, and others extended over two world wars, enriching their lives and facilitating their research. Even the dispute--the "war of the sparks and the soups"--between neurophysiologists and pharmacologists over whether synaptic transmission is electrical or chemical played a positive role in stimulating the research needed to provide convincing proof. The Discovery of Chemical Neurotransmitters Elliot Valenstein doi:10.1006/brcg.2001.1487 Brain and Cognition, Vol. 49, No. 1. (June 2002), pp. 73-95. 2008-05-12T11:17:36-00:00 Brain and Cognition 49 1 73 95 history-of-science philosophy-of-science sparks-vs-soups http://www.citeulike.org/user/awooga/article/2761137 <i>Brain, Behavior, and Immunity, Vol. In Press, Corrected Proof</i> Brief Commentary: Autistic children: A neuroimmune perspective Robert Dantzer Keith Kelley doi:10.1016/j.bbi.2008.03.001 Brain, Behavior, and Immunity, Vol. In Press, Corrected Proof 2008-05-06T13:26:59-00:00 Brain, Behavior, and Immunity In Press, Corrected Proof autism immunology http://www.citeulike.org/user/awooga/article/2737506 <i>(30 June 1978)</i><br /><br /><P>The author of the world wide best-seller, <I>Small Is Beautiful,</I> 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. <P>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. <P><I>A Guide for the Perplexed</I> 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. Guide for the Perplexed EF Schumacher (30 June 1978) 2008-04-30T10:42:03-00:00 Harper Perennial no-tag http://www.citeulike.org/user/awooga/article/329647 <i>Nature Immunology, Vol. 6, No. 10. (21 September 2005), pp. 973-979.</i> Are innate immune signaling pathways in plants and animals conserved? Frederick Ausubel doi:10.1038/ni1253 Nature Immunology, Vol. 6, No. 10. (21 September 2005), pp. 973-979. 2005-09-22T05:54:07-00:00 Nature Immunology 1529-2908 6 10 973 979 Nature Publishing Group immunology http://www.citeulike.org/user/awooga/article/945537 <i>Nature, Vol. 444, No. 7117., pp. 323-329.</i> The plant immune system Jonathan Jones Jeffery Dangl doi:10.1038/nature05286 Nature, Vol. 444, No. 7117., pp. 323-329. 2006-11-16T03:45:43-00:00 Nature 0028-0836 444 7117 323 329 Nature Publishing Group immunology http://www.citeulike.org/user/awooga/article/2531838 <i>Science, Vol. 319, No. 5869. (14 March 2008), pp. 1543-1546.</i><br /><br />It is usually assumed that enhanced spiking activity in the form of persistent reverberation for several seconds is the neural correlate of working memory. Here, we propose that working memory is sustained by calcium-mediated synaptic facilitation in the recurrent connections of neocortical networks. In this account, the presynaptic residual calcium is used as a buffer that is loaded, refreshed, and read out by spiking activity. Because of the long time constants of calcium kinetics, the refresh rate can be low, resulting in a mechanism that is metabolically efficient and robust. The duration and stability of working memory can be regulated by modulating the spontaneous activity in the network. 10.1126/science.1150769 Synaptic Theory of Working Memory Gianluigi Mongillo Omri Barak Misha Tsodyks doi:10.1126/science.1150769 Science, Vol. 319, No. 5869. (14 March 2008), pp. 1543-1546. 2008-03-14T12:03:46-00:00 Science 319 5869 1543 1546 depression facilitation model working-memory http://www.citeulike.org/user/awooga/article/2615899 <i>Neuron, Vol. 57, No. 6. (27 March 2008), pp. 930-941.</i><br /><br />Summary Food palatability and hedonic value play central roles in nutrient intake. However, postingestive effects can influence food preferences independently of palatability, although the neurobiological bases of such mechanisms remain poorly understood. Of central interest is whether the same brain reward circuitry that is responsive to palatable rewards also encodes metabolic value independently of taste signaling. Here we show that trpm5-/- mice, which lack the cellular machinery required for sweet taste transduction, can develop a robust preference for sucrose solutions based solely on caloric content. Sucrose intake induced dopamine release in the ventral striatum of these sweet-blind mice, a pattern usually associated with receipt of palatable rewards. Furthermore, single neurons in this same ventral striatal region showed increased sensitivity to caloric intake even in the absence of gustatory inputs. Our findings suggest that calorie-rich nutrients can directly influence brain reward circuits that control food intake independently of palatability or functional taste transduction. Food Reward in the Absence of Taste Receptor Signaling Ivan de Araujo Albino Oliveira-Maia Tatyana Sotnikova Raul Gainetdinov Marc Caron Miguel Nicolelis Sidney Simon doi:10.1016/j.neuron.2008.01.032 Neuron, Vol. 57, No. 6. (27 March 2008), pp. 930-941. 2008-03-31T11:10:48-00:00 Neuron 57 6 930 941 dopamine reinforcement-learning reward taste http://www.citeulike.org/user/awooga/article/2568705 <i>Nature Reviews Neuroscience, Vol. 9, No. 4., pp. 314-320.</i> A common neurobiology for pain and pleasure Siri Leknes Irene Tracey doi:10.1038/nrn2333 Nature Reviews Neuroscience, Vol. 9, No. 4., pp. 314-320. 2008-03-21T04:33:30-00:00 Nature Reviews Neuroscience 1471-003X 9 4 314 320 Nature Publishing Group pain reinforcment-learning review reward http://www.citeulike.org/user/awooga/article/2605796 <i>Cereb. Cortex, Vol. 6, No. 3. (1 May 1996), pp. 406-416.</i><br /><br />Population coding, where neurons with broad and overlapping firing rate tuning curves collectively encode information about a stimulus, is a common feature of sensory systems. We use decoding methods and measured properties of NMDA-mediated LTP induction to study the impact of long-term potentiation of synapses between the neurons of such a coding array. We find that, due to a temporal asymmetry in the induction of NMDA-mediated LTP, firing patterns in a neuronal array that initially represent the current value of a sensory input will, after training, provide an experienced-based prediction of that input instead. We compute how this prediction arises from and depends on the training experience. We also show how the encoded prediction can be used to generate learned motor sequences, such as the movement of a limb. This involves a novel form of memory recall that is driven by the motor response so that it automatically generates new information at a rate appropriate for the task being performed. 10.1093/cercor/6.3.406 Functional Significance of Long-Term Potentiation for Sequence Learning and Prediction Abbott Kenneth Blum doi:10.1093/cercor/6.3.406 Cereb. Cortex, Vol. 6, No. 3. (1 May 1996), pp. 406-416. 2008-03-28T10:43:33-00:00 Cereb. Cortex 6 3 406 416 calcium line-attractor ltp nmda plasticity stdp http://www.citeulike.org/user/awooga/article/2586231 <i>Proceedings of the National Academy of Sciences, Vol. 101, No. 41. (12 October 2004), pp. 14943-14948.</i><br /><br />Modifications in the strengths of synapses are thought to underlie memory, learning, and development of cortical circuits. Many cellular mechanisms of synaptic plasticity have been investigated in which differential elevations of postsynaptic calcium concentrations play a key role in determining the direction and magnitude of synaptic changes. We have previously described a model of plasticity that uses calcium currents mediated by N-methyl-D-aspartate receptors as the associative signal for Hebbian learning. However, this model is not completely stable. Here, we propose a mechanism of stabilization through homeostatic regulation of intracellular calcium levels. With this model, synapses are stable and exhibit properties such as those observed in metaplasticity and synaptic scaling. In addition, the model displays synaptic competition, allowing structures to emerge in the synaptic space that reflect the statistical properties of the inputs. Therefore, the combination of a fast calcium-dependent learning and a slow stabilization mechanism can account for both the formation of selective receptive fields and the maintenance of neural circuits in a state of equilibrium. 10.1073/pnas.0405555101 Synaptic homeostasis and input selectivity follow from a calcium-dependent plasticity model Luk Yeung Harel Shouval Brian Blais Leon Cooper doi:10.1073/pnas.0405555101 Proceedings of the National Academy of Sciences, Vol. 101, No. 41. (12 October 2004), pp. 14943-14948. 2008-03-25T15:19:22-00:00 Proceedings of the National Academy of Sciences 101 41 14943 14948 no-tag http://www.citeulike.org/user/awooga/article/2567765 <i>Proc Natl Acad Sci U S A, Vol. 99, No. 16. (6 August 2002), pp. 10831-10836.</i><br /><br />Synapses in the brain are bidirectionally modifiable, but the routes of induction are diverse. In various experimental paradigms, N-methyl-d-aspartate receptor-dependent long-term depression and long-term potentiation have been induced selectively by varying the membrane potential of the postsynaptic neurons during presynaptic stimulation of a constant frequency, the rate of presynaptic stimulation, and the timing of pre- and postsynaptic action potentials. In this paper, we present a mathematical embodiment of bidirectional synaptic plasticity that is able to explain diverse induction protocols with a fixed set of parameters. The key assumptions and consequences of the model can be tested experimentally; further, the model provides the foundation for a unified theory of N-methyl-d-aspartate receptor-dependent synaptic plasticity. A unified model of NMDA receptor-dependent bidirectional synaptic plasticity. HZ Shouval MF Bear LN Cooper doi:10.1073/pnas.152343099 Proc Natl Acad Sci U S A, Vol. 99, No. 16. (6 August 2002), pp. 10831-10836. 2008-03-20T17:42:30-00:00 Proc Natl Acad Sci U S A 0027-8424 99 16 10831 10836 no-tag http://www.citeulike.org/user/awooga/article/2485632 <i>Nat Neurosci, Vol. 1, No. 4. (August 1998), pp. 310-317.</i><br /><br />When monkeys perform a delayed match-to-sample task, some neurons in the anterior inferotemporal cortex show sustained activity following the presentation of specific visual stimuli, typically only those that are shown repeatedly. When sample stimuli are shown in a fixed temporal order, the few images that evoke delay activity in a given neuron are often neighboring stimuli in the sequence, suggesting that this delay activity may be the neural correlate of associative long-term memory. Here we report that stimulus-selective sustained activity is also evident following the presentation of the test stimulus in the same task. We use a neural network model to demonstrate that persistent stimulus-selective activity across the intertrial interval can lead to similar mnemonic representations (distributions of delay activity across the neural population) for neighboring visual stimuli. Thus, inferotemporal cortex may contain neural machinery for generating long-term stimulus-stimulus associations. Inter-trial neuronal activity in inferior temporal cortex: a putative vehicle to generate long-term visual associations. V Yakovlev S Fusi E Berman E Zohary doi:10.1038/1131 Nat Neurosci, Vol. 1, No. 4. (August 1998), pp. 310-317. 2008-03-07T16:45:09-00:00 Nat Neurosci 1097-6256 1 4 310 317 inferior-temporal-cortex working-memory http://www.citeulike.org/user/awooga/article/2558158 <i>Neuron, Vol. 32, No. 6. (20 December 2001), pp. 1149-1164.</i><br /><br />Cortical long-term plasticity depends on firing rate, spike timing, and cooperativity among inputs, but how these factors interact during realistic patterns of activity is unknown. Here we monitored plasticity while systematically varying the rate, spike timing, and number of coincident afferents. These experiments demonstrate a novel form of cooperativity operating even when postsynaptic firing is evoked by current injection, and reveal a complex dependence of LTP and LTD on rate and timing. Based on these data, we constructed and tested three quantitative models of cortical plasticity. One of these models, in which spike-timing relationships causing LTP "win" out over those favoring LTD, closely fits the data and accurately predicts the build-up of plasticity during random firing. This provides a quantitative framework for predicting the impact of in vivo firing patterns on synaptic strength. Rate, Timing, and Cooperativity Jointly Determine Cortical Synaptic Plasticity Per Sjostrom Gina Turrigiano Sacha Nelson doi:10.1016/S0896-6273(01)00542-6 Neuron, Vol. 32, No. 6. (20 December 2001), pp. 1149-1164. 2008-03-19T11:19:26-00:00 Neuron 32 6 1149 1164 no-tag http://www.citeulike.org/user/awooga/article/2558159 <i>Current Opinion in Neurobiology, Vol. 12, No. 3. (1 June 2002), pp. 305-314.</i><br /><br />Plasticity at central synapses depends critically on the timing of presynaptic and postsynaptic action potentials. Key initial steps in synaptic plasticity involve the back-propagation of action potentials into the dendritic tree and calcium influx that depends nonlinearly on the action potential and synaptic input. These initial steps are now better understood. In addition, recent studies of processes as diverse as gene expression and channel inactivation suggest that responses to calcium transients depend not only their amplitude, but on their time course and on the location of their origin. Spike timing, calcium signals and synaptic plasticity Per Sjostrom Sacha Nelson doi:10.1016/S0959-4388(02)00325-2 Current Opinion in Neurobiology, Vol. 12, No. 3. (1 June 2002), pp. 305-314. 2008-03-19T11:19:32-00:00 Current Opinion in Neurobiology 12 3 305 314 calcium model plasticity review http://www.citeulike.org/user/awooga/article/2523192 <i>Neuron, Vol. 57, No. 5. (13 March 2008), pp. 760-773.</i><br /><br />Summary The mesocorticolimbic dopamine system is essential for cognitive and emotive brain functions and is thus an important target in major brain diseases like schizophrenia, drug addiction, and attention deficit hyperactivity disorder. However, the cellular basis for the diversity in behavioral functions and associated dopamine-release pattern within the mesocorticolimbic system has remained unclear. Here, we report the identification of a type of dopaminergic neuron within the mesocorticolimbic dopamine system with unconventional fast-firing properties and small DAT/TH mRNA expression ratios that selectively projects to prefrontal cortex and nucleus accumbens core and medial shell as well as to basolateral amygdala. In contrast, well-described conventional slow-firing dopamine midbrain neurons only project to the lateral shell of the nucleus accumbens and the dorsolateral striatum. Among this dual dopamine midbrain system defined in this study by converging anatomical, electrophysiological, and molecular properties, mesoprefrontal dopaminergic neurons are unique, as only they do not possess functional somatodendritic Girk2-coupled dopamine D2 autoreceptors. Unique Properties of Mesoprefrontal Neurons within a Dual Mesocorticolimbic Dopamine System Stephan Lammel Andrea Hetzel Olga Hackel Ian Jones Birgit Liss Jochen Roeper doi:10.1016/j.neuron.2008.01.022 Neuron, Vol. 57, No. 5. (13 March 2008), pp. 760-773. 2008-03-13T00:38:04-00:00 Neuron 57 5 760 773 autoreceptors cortex d2-receptor dopamine substantia-nigra vta http://www.citeulike.org/user/awooga/article/2545894 <i>(02 October 1980)</i><br /><br />In this book van Fraassen develops an alternative to scientific realism by constructing and evaluating three mutually reinforcing theories. The Scientific Image (Clarendon Library of Logic & Philosophy) Bas (02 October 1980) 2008-03-17T12:58:56-00:00 Oxford University Press, USA philosophy-of-science http://www.citeulike.org/user/awooga/article/2463021 <i>J Neurophysiol, Vol. 98, No. 6. (1 December 2007), pp. 3731-3748.</i><br /><br />Dopaminergic modulation produces a variety of functional changes in the principal cell of the striatum, the medium spiny neuron (MSN). Using a 189-compartment computational model of a ventral striatal MSN, we simulated whole cell D1- and D2-receptormediated modulation of both intrinsic (sodium, calcium, and potassium) and synaptic currents (AMPA and NMDA). Dopamine (DA) modulations in the model were based on a review of published experiments in both ventral and dorsal striatum. To objectively assess the net effects of DA modulation, we combined reported individual channel modulations into either D1- or D2-receptor modulation conditions and studied them separately. Contrary to previous suggestions, we found that D1 modulation had no effect on MSN nonlinearity and could not induce bistability. In agreement with previous suggestions, we found that dopaminergic modulation leads to changes in input filtering and neuronal excitability. Importantly, the changes in neuronal excitability agree with the classical model of basal ganglia function. We also found that DA modulation can alter the integration time window of the MSN. Interestingly, the effects of DA modulation of synaptic properties opposed the effects of DA modulation of intrinsic properties, with the synaptic modulations generally dominating the net effect. We interpret this lack of synergy to suggest that the regulation of whole cell integrative properties is not the primary functional purpose of DA. We suggest that D1 modulation might instead primarily regulate calcium influx to dendritic spines through NMDA and L-type calcium channels, by both direct and indirect mechanisms. 10.1152/jn.00335.2007 Effects of Dopaminergic Modulation on the Integrative Properties of the Ventral Striatal Medium Spiny Neuron Jason Moyer John Wolf Leif Finkel doi:10.1152/jn.00335.2007 J Neurophysiol, Vol. 98, No. 6. (1 December 2007), pp. 3731-3748. 2008-03-04T03:40:49-00:00 J Neurophysiol 98 6 3731 3748 dopamine medium-spiny-neurons model striatum http://www.citeulike.org/user/awooga/article/1421135 <i>Annals of the New York Academy of Sciences, Vol. 1104, No. 1. (May 2007), pp. 310-323.</i> Reward Prediction Error Computation in the Pedunculopontine Tegmental Nucleus Neurons Yasushi Kobayashi Ken-Ichi Okada doi:10.1196/annals.1390.003 Annals of the New York Academy of Sciences, Vol. 1104, No. 1. (May 2007), pp. 310-323. 2007-06-29T02:35:43-00:00 Annals of the New York Academy of Sciences 0077-8923 1104 1 310 323 Blackwell Publishing acetylcholine dopamine pptg reinforcement-learning http://www.citeulike.org/user/awooga/article/2500656 <i>Autoimmunity Reviews, Vol. 6, No. 1. (November 2006), pp. 54-60.</i><br /><br />Aside from its recognition and warning functions, olfaction serves many purposes in the CNS and remains one of the most important means of communication with the environment. In addition to olfactory tract input, the olfactory bulb also receives and provides input to other brain centers that modify neuronal activity. Research in the field of immunology as well as in various brain illnesses is beginning to indicate the increasing relevance of smell in pathophysiology. Much of this is based on the many intricate interactions that exist between the immune system and the nervous system, and evidence exists that there may be something unique about the olfactory system that is inextricably related to immunological function. In addition, accumulating evidence confirms the existence of olfactory dysfunction in brain disease, much of which appears at early stages including multiple sclerosis, Alzheimer's Disease, Parkinson's Disease, schizophrenia and depression. Such observations may further suggest that under certain circumstances, olfactory abnormalities may be associated with autoimmune conditions. Since the organization of the olfactory system is so sensitive, impairment may be noted at an early stage. This may become important in the prediction of certain brain illnesses. While preliminary evidence may suggest a role for olfaction in the management and alleviation of various disorders, investigation of its clinical relevance remains limited. To smell the immune system: Olfaction, autoimmunity and brain involvement Rael Strous Yehuda Shoenfeld doi:10.1016/j.autrev.2006.07.002 Autoimmunity Reviews, Vol. 6, No. 1. (November 2006), pp. 54-60. 2008-03-10T13:07:53-00:00 Autoimmunity Reviews 6 1 54 60 olfaction psychoneuroimmunology http://www.citeulike.org/user/awooga/article/2500354 <i>Parkinsonism & Related Disorders, Vol. 10, No. Supplement 1. (May 2004), pp. S3-S7.</i><br /><br />The immunohistochemical demonstration of reactive microglia and activated complement components suggests that chronic inflammation occurs in affected brain regions in Parkinson's disease (PD). Evidence from humans and monkeys exposed to MPTP indicates this inflammation may persist many years after the initial stimulus has disappeared. Chronic inflammation can damage host cells. Reports in the literature indicate that antiinflammatory agents inhibit dopaminergic cell death in animal models of PD, and there is one epidemiological report that their use significantly diminishes the risk of PD in humans. There is a marked elevation in the mRNA levels for complement proteins and markers of activated microglia in affected regions in PD. The upregulation appears greater than that found in inflamed arthritic joints. These data support the hypothesis that chronic inflammation may play an important role, if secondary, in the pathogenesis of PD. Inflammation and neurodegeneration in Parkinson's disease Patrick Mcgeer Edith Mcgeer doi:10.1016/j.parkreldis.2004.01.005 Parkinsonism & Related Disorders, Vol. 10, No. Supplement 1. (May 2004), pp. S3-S7. 2008-03-10T12:34:24-00:00 Parkinsonism & Related Disorders 10 Supplement 1 S3 S7 parkinsons psychoneuroimmunology http://www.citeulike.org/user/awooga/article/2486163 <i>Experimental Neurology, Vol. 83, No. 2. (February 1984), pp. 367-377.</i><br /><br />Abstract The activity of dopamine-containing ventral tegmental area (VTA) units was recorded by means of movable 32- and 64-[mu]m-diameter insulated Nichrome wires in freely moving cats. The VTA units displayed a slow, somewhat irregular activity during quiet waking (mean 3.63 +/- 0.41 spikes/s) and showed no significant change in activity during slow-wave sleep or REM sleep. Although VTA unit activity was somewhat higher and more erratic during active waking, there was no relationship between unit discharge and phasic movement. These neurons were inhibited (-87%) by small doses of apomorphine (1.0 mg/kg, i.p.) and excited (+43%) by small doses of haloperidol (0.5 mg/kg, i.p.). The stress of a conditioned emotional reaction (CER) paradigm resulted in a significant increase in the discharge rate of VTA neurons (+39%), compared with the quiet-waking baseline. The CER paradigm increased plasma glucocorticoids by 74%. Neurochemical studies revealed that the CER paradigm resulted in a significant decrease of dopamine in the limbic forebrain (-31%), whereas both homovanillic acid (+47%) and dihydroxyphenylacetic acid (+43%) concentrations were increased. No significant changes in dopamine metabolism were observed in the striatum under the CER situation. These data have implications in relation to the role of stress and dopamine in mediating certain psychiatric disorders. Dopamine-containing ventral tegmental area neurons in freely moving cats: Activity during the sleep-waking cycle and effects of stress Michael Trulson Donald Preussler doi:10.1016/S0014-4886(84)90105-5 Experimental Neurology, Vol. 83, No. 2. (February 1984), pp. 367-377. 2008-03-07T17:22:07-00:00 Experimental Neurology 83 2 367 377 dopamine electrophysiology sleep vta http://www.citeulike.org/user/awooga/article/2484780 <i>(29 January 2008)</i><br /><br /><B>The masterpiece of the father of modern philosophy</B> <BR><BR> A seminal text of modern philosophy, Immanuel Kants <I>Critique of Pure Reason</I> (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. Critique of Pure Reason (Penguin Classics) Immanuel Kant (29 January 2008) 2008-03-07T14:50:43-00:00 Penguin Classics no-tag http://www.citeulike.org/user/awooga/article/2483849 <i>Brain Research, Vol. 731, No. 1-2. (26 August 1996), pp. 1-11.</i><br /><br />Systemic administration of interleukin-2 (IL-2) provoked marked alterations of responding for rewarding brain stimulation from the medial forebrain bundle (MFB). In particular, when animals were tested for ICSS immediately following IL-2 treatment only a modest disturbance of responding was evident. However, if animals were subsequently exposed to repeated daily ICSS sessions (24-168 h) in the drug-free state, rightward shifts in the rate intensity functions and significant increases in reward thresholds were apparent. These results were dependent upon the presence of IL-2 during the initial ICSS session. If animals were tested for ICSS 24 h after IL-2 administration, without an intervening test, performance was unaffected. Evaluation of nonreinforced behavior after IL-2 treatment revealed that ICSS remained under stimulus control and the cytokine did not provoke reward-unrelated performance deficits. Dopamine (DA) activity in the nucleus accumbens has been implicated in goal-directed responding to positively reinforcing stimuli and in the present investigation, using in vivo microdialysis, it was observed that IL-2 markedly reduced DA release from this region. It was suggested that the protracted consequences of IL-2 on ICSS likely do not involve motoric, soporific, attentional or cognitive changes, but may be attributable to its specific actions on motivational arousal, possibly engendered by the cytokine-induced diminution of accumbal DA efflux. Interleukin-2 decreases accumbal dopamine efflux and responding for rewarding lateral hypothalamic stimulation Hymie Anisman L Kokkinidis Z Merali doi:10.1016/0006-8993(96)00460-X Brain Research, Vol. 731, No. 1-2. (26 August 1996), pp. 1-11. 2008-03-07T12:28:16-00:00 Brain Research 731 1-2 1 11 cytokines dopamine hypothalamus immunology neuromodulation http://www.citeulike.org/user/awooga/article/2483856 <i>J. Neurosci., Vol. 13, No. 8. (1 August 1993), pp. 3574-3581.</i> Interleukin-1 beta augments release of norepinephrine, dopamine, and serotonin in the rat anterior hypothalamus F Shintani S Kanba T Nakaki M Nibuya N Kinoshita E Suzuki G Yagi R Kato M Asai J. Neurosci., Vol. 13, No. 8. (1 August 1993), pp. 3574-3581. 2008-03-07T12:29:37-00:00 J. Neurosci. 13 8 3574 3581 cytokines dopamine hypothalamus immunology neuromodulation noradrenaline serotonin http://www.citeulike.org/user/awooga/article/2483816 <i>Neuroscience & Biobehavioral Reviews, Vol. 24, No. 3. (May 2000), pp. 295-340.</i><br /><br />Both neurons and glia interact dynamically to enable information processing and behaviour. They have had increasingly intimate, numerous and differentiated associations during brain evolution. Radial glia form a scaffold for neuronal developmental migration and astrocytes enable later synapse elimination. Functionally syncytial glial cells are depolarised by elevated potassium to generate slow potential shifts that are quantitatively related to arousal, levels of motivation and accompany learning. Potassium stimulates astrocytic glycogenolysis and neuronal oxidative metabolism, the former of which is necessary for passive avoidance learning in chicks. Neurons oxidatively metabolise lactate/pyruvate derived from astrocytic glycolysis as their major energy source, stimulated by elevated glutamate. In astrocytes, noradrenaline activates both glycogenolysis and oxidative metabolism. Neuronal glutamate depends crucially on the supply of astrocytically derived glutamine. Released glutamate depolarises astrocytes and their handling of potassium and induces waves of elevated intracellular calcium. Serotonin causes astrocytic hyperpolarisation. Astrocytes alter their physical relationships with neurons to regulate neuronal communication in the hypothalamus during lactation, parturition and dehydration and in response to steroid hormones. There is also structural plasticity of astrocytes during learning in cortex and cerebellum. Neuronal-glial interactions and behaviour PR Laming H Kimelberg S Robinson A Salm N Hawrylak C Muller B Roots K Ng doi:10.1016/S0149-7634(99)00080-9 Neuroscience & Biobehavioral Reviews, Vol. 24, No. 3. (May 2000), pp. 295-340. 2008-03-07T12:20:57-00:00 Neuroscience & Biobehavioral Reviews 24 3 295 340 glia review http://www.citeulike.org/user/awooga/article/2483809 <i>Glia, Vol. 40, No. 2. (2002), pp. 140-155.</i><br /><br />Cytokines constitute a significant portion of the immuno- and neuromodulatory messengers that can be released by activated microglia. By virtue of potent effects on resident and invading cells, microglial cyto- and chemokines regulate innate defense mechanisms, help the initiation and influence the type of immune responses, participate in the recruitment of leukocytes to the CNS, and support attempts of tissue repair and recovery. Microglia can also receive cyto- and chemokine signals as part of auto- and paracrine communications with astrocytes, neurons, the endothelium, and leukocyte infiltrates. Strong responses and modulatory influences can be demonstrated, adding to the emerging view that microglial behavior is highly dependent on the (cytokine) environment and that reactions to a challenge may vary with the stimulation context. In principle, microglial activation aims at CNS protection. However, failed microglial engagement due to excessive or sustained activation could significantly contribute to acute and chronic neuropathologies. Dysregulation of microglial cytokine production could thereby promote harmful actions of the defense mechanisms, result in direct neurotoxicity, as well as disturb neural cell functions as they are sensitive to cytokine signaling. GLIA 40:140-155, 2002. © 2002 Wiley-Liss, Inc. Microglia as a source and target of cytokines Uwe-Karsten Hanisch doi:10.1002/glia.10161 Glia, Vol. 40, No. 2. (2002), pp. 140-155. 2008-03-07T12:17:49-00:00 Glia 40 2 140 155 cytokines glia immunology http://www.citeulike.org/user/awooga/article/86821 <i>Science, Vol. 304, No. 5678. (18 June 2004), pp. 1782-1787.</i><br /><br />Psychologists and economists have long appreciated the contribution of reward history and expectation to decision-making. Yet we know little about how specific histories of choice and reward lead to an internal representation of the "value" of possible actions. We approached this problem through an integrated application of behavioral, computational, and physiological techniques. Monkeys were placed in a dynamic foraging environment in which they had to track the changing values of alternative choices through time. In this context, the monkeys' foraging behavior provided a window into their subjective valuation. We found that a simple model based on reward history can duplicate this behavior and that neurons in the parietal cortex represent the relative value of competing actions predicted by this model. Matching Behavior and the Representation of Value in the Parietal Cortex Leo Sugrue Greg Corrado William Newsome doi:10.1126/science.1094765 Science, Vol. 304, No. 5678. (18 June 2004), pp. 1782-1787. 2005-02-01T17:44:21-00:00 Science 304 5678 1782 1787 attention dopamine lip neuroeconomics parietal-cortex http://www.citeulike.org/user/awooga/article/87188 <i>Neuron, Vol. 44, No. 2. (14 October 2004), pp. 365-378.</i><br /><br />Behavioral studies suggest that making a decision involves representing the overall desirability of all available actions and then selecting that action that is most desirable. Physiological studies have proposed that neurons in the parietal cortex play a role in selecting movements for execution. To test the hypothesis that these parietal neurons encode the subjective desirability of making particular movements, we exploited Nash's game theoretic equilibrium, during which the subjective desirability of multiple actions should be equal for human players. Behavior measured during a strategic game suggests that monkeys' choices, like those of humans, are guided by subjective desirability. Under these conditions, activity in the parietal cortex was correlated with the relative subjective desirability of actions irrespective of the specific combination of reward magnitude, reward probability, and response probability associated with each action. These observations may help place many recent findings regarding the posterior parietal cortex into a common conceptual framework. Activity in posterior parietal cortex is correlated with the relative subjective desirability of action. MC Dorris PW Glimcher doi:10.1016/j.neuron.2004.09.009 Neuron, Vol. 44, No. 2. (14 October 2004), pp. 365-378. 2005-02-04T21:13:00-00:00 Neuron 0896-6273 44 2 365 378 attention dopamine lip neuroeconomics parietal-cortex http://www.citeulike.org/user/awooga/article/86865 <i>Nature, Vol. 400, No. 6741. (15 July 1999), pp. 233-238.</i><br /><br />Decision theory proposes that humans and animals decide what to do in a given situation by assessing the relative value of each possible response. This assessment can be computed, in part, from the probability that each action will result in a gain and the magnitude of the gain expected. Here we show that the gain (or reward) a monkey can expect to realize from an eye-movement response modulates the activity of neurons in the lateral intraparietal area, an area of primate cortex that is thought to transform visual signals into eye-movement commands. We also show that the activity of these neurons is sensitive to the probability that a particular response will result in a gain. When animals can choose freely between two alternative responses, the choices subjects make and neuronal activation in this area are both correlated with the relative amount of gain that the animal can expect from each response. Our data indicate that a decision-theoretic model may provide a powerful new framework for studying the neural processes that intervene between sensation and action. Neural correlates of decision variables in parietal cortex. ML Platt PW Glimcher doi:10.1038/22268 Nature, Vol. 400, No. 6741. (15 July 1999), pp. 233-238. 2005-02-01T19:51:55-00:00 Nature 0028-0836 400 6741 233 238 attention dopamine lip neuroeconomics parietal-cortex http://www.citeulike.org/user/awooga/article/1421137 <i>Annals of the New York Academy of Sciences, Vol. 1104, No. 1. (May 2007), pp. 289-300.</i> Serotonin and the Evaluation of Future Rewards: Theory, Experiments, and Possible Neural Mechanisms Nicolas Schweighofer Saori Tanaka Kenji Doya doi:10.1196/annals.1390.011 Annals of the New York Academy of Sciences, Vol. 1104, No. 1. (May 2007), pp. 289-300. 2007-06-29T02:35:43-00:00 Annals of the New York Academy of Sciences 0077-8923 1104 1 289 300 Blackwell Publishing model reinforcement-learning serotonin http://www.citeulike.org/user/awooga/article/1237233 <i>Current Opinion in Neurobiology, Vol. 16, No. 2. (April 2006), pp. 199-204.</i><br /><br />Following the suggestion that midbrain dopaminergic neurons encode a signal, known as a `reward prediction error', used by artificial intelligence algorithms for learning to choose advantageous actions, the study of the neural substrates for reward-based learning has been strongly influenced by computational theories. In recent work, such theories have been increasingly integrated into experimental design and analysis. Such hybrid approaches have offered detailed new insights into the function of a number of brain areas, especially the cortex and basal ganglia. In part this is because these approaches enable the study of neural correlates of subjective factors (such as a participant's beliefs about the reward to be received for performing some action) that the computational theories purport to quantify. The computational neurobiology of learning and reward Nathaniel Daw Kenji Doya doi:10.1016/j.conb.2006.03.006 Current Opinion in Neurobiology, Vol. 16, No. 2. (April 2006), pp. 199-204. 2007-04-19T16:11:56-00:00 Current Opinion in Neurobiology 16 2 199 204 dopamine model reinforcement-learning serotonin http://www.citeulike.org/user/awooga/article/1926528 <i>Neural Netw, Vol. 19, No. 8. (October 2006), pp. 1153-1160.</i><br /><br />Most reinforcement learning models of animal conditioning operate under the convenient, though fictive, assumption that Pavlovian conditioning concerns prediction learning whereas instrumental conditioning concerns action learning. However, it is only through Pavlovian responses that Pavlovian prediction learning is evident, and these responses can act against the instrumental interests of the subjects. This can be seen in both experimental and natural circumstances. In this paper we study the consequences of importing this competition into a reinforcement learning context, and demonstrate the resulting effects in an omission schedule and a maze navigation task. The misbehavior created by Pavlovian values can be quite debilitating; we discuss how it may be disciplined. The misbehavior of value and the discipline of the will. P Dayan Y Niv B Seymour ND Daw doi:10.1016/j.neunet.2006.03.002 Neural Netw, Vol. 19, No. 8. (October 2006), pp. 1153-1160. 2007-11-16T14:12:57-00:00 Neural Netw 0893-6080 19 8 1153 1160 instinct misbehaviour reinforcement-learning http://www.citeulike.org/user/awooga/article/2478911 <i>Am J Psychiatry, Vol. 163, No. 1. (1 January 2006), pp. 8-11.</i><br /><br />10.1176/appi.ajp.163.1.8 SERT-ainly Involved in Depression, But When? Etienne Sibille David Lewis doi:10.1176/appi.ajp.163.1.8 Am J Psychiatry, Vol. 163, No. 1. (1 January 2006), pp. 8-11. 2008-03-06T14:17:29-00:00 Am J Psychiatry 163 1 8 11 depression serotonin ssris http://www.citeulike.org/user/awooga/article/2478869 <i>J Pharmacol Exp Ther, Vol. 271, No. 1. (October 1994), pp. 83-90.</i><br /><br />Electrophysiological techniques were used to study the effects of various serotonin (5-HT) agonists and antagonists on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) of rats. Systemic administration of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1.25-80 micrograms/kg i.v.) increased the firing rate of the majority (75%) of DA cells studied and stimulated their bursting activity. A subpopulation (25%) of DA neurons was inhibited by 8-OH-DPAT. Selective lesions of 5-HT neurons by the neurotoxin 5-7-dihydroxytryptamine abolished completely the excitatory effect of 8-OH-DPAT on both firing rate and bursting activity of DA neurons. Microiontophoretic application of 8-OH-DPAT into the VTA did not cause any change in the firing rate of DA neurons. Treatment with the selective 5-HT1B agonist CGS 12066B (7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrolo[1,2-a] quinoxaline 1:2 maleate salt) (1.25-160 micrograms/kg i.v.) did not cause any change in basal firing rate of VTA DA cells. Systemic administration of trifluoromethylphenylpiperazine (TFMPP) (1.25-160 micrograms/kg i.v.) and m-chlorophenylpiperazine (mCPP) (1.25-320 micrograms/kg i.v.), two mixed 5-HT1B/5-HT1C receptor agonists, significantly reduced the firing rate of all VTA DA neurons studied. The effect of mCPP (maximal inhibition, 40%) was more pronounced compared to that of TFMPP (maximal inhibition, 25%). Microiontophoretic application of mCPP into the VTA caused a marked inhibition of the basal activity of DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS) Serotonin-dopamine interaction in the rat ventral tegmental area: an electrophysiological study in vivo. S Prisco S Pagannone E Esposito J Pharmacol Exp Ther, Vol. 271, No. 1. (October 1994), pp. 83-90. 2008-03-06T14:00:30-00:00 J Pharmacol Exp Ther 0022-3565 271 1 83 90 dopamine electrophysiology in-vivo serotonin vta http://www.citeulike.org/user/awooga/article/2478871 <i>Trends in Pharmacological Sciences, Vol. 22, No. 5. (1 May 2001), pp. 229-232.</i><br /><br />Substantial evidence suggests that the functional status of the mesocorticolimbic dopamine (DA) system originating in the ventral tegmental area is under a phasic and tonic inhibitory control by the 5-HT system that acts by stimulating 5-HT2C receptor subtypes. Indeed, electrophysiological and biochemical data demonstrate that 5-HT2C receptor agonists decrease, whereas 5-HT2C receptor antagonists enhance, mesocorticolimbic DA function. However, 5-HT2C receptors do not appear to play a relevant role in the control of the nigrostriatal DA system originating in the substantia nigra pars compacta. In this article, the role of 5-HT2C receptors in the control of brain DA function will be reviewed, and the search for new therapies for neuropsychiatric disorders, such as depression, schizophrenia and drug addiction, based on these findings will be discussed. Role of 5-HT2C receptors in the control of central dopamine function Vincenzo Di Matteo Antonio De Blasi Camillo Di Giulio Ennio Esposito doi:10.1016/S0165-6147(00)01688-6 Trends in Pharmacological Sciences, Vol. 22, No. 5. (1 May 2001), pp. 229-232. 2008-03-06T14:00:35-00:00 Trends in Pharmacological Sciences 22 5 229 232 dopamine serotonin vta http://www.citeulike.org/user/awooga/article/2478691 <i>Psychological Review (0 1973)</i><br /><br />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) On the Psychology of Prediction Daniel Kahneman Amos Tversky Psychological Review (0 1973) 2008-03-06T13:04:23-00:00 Psychological Review no-tag http://www.citeulike.org/user/awooga/article/2478580 <i>Psychol Rev, Vol. 81, No. 2. (March 1974), pp. 119-145.</i> An opponent-process theory of motivation. I. Temporal dynamics of affect. RL Solomon JD Corbit Psychol Rev, Vol. 81, No. 2. (March 1974), pp. 119-145. 2008-03-06T12:24:57-00:00 Psychol Rev 0033-295X 81 2 119 145 no-tag http://www.citeulike.org/user/awooga/article/2478453 <i>Sleep Medicine Reviews, Vol. 11, No. 2. (April 2007), pp. 113-133.</i><br /><br />Summary Dopamine (DA)-containing neurons involved in the regulation of sleep and waking (W) arise in the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc). The VTA and SNc cells have efferent and afferent connections with the dorsal raphe nucleus (DRN), the pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT), the locus coeruleus (LC), the lateral and posterior hypothalamus (LH), the basal forebrain (BFB), and the thalamus. Molecular cloning techniques have enabled the characterization of two distinct groups of DA receptors, D1-like and D2-like receptors. The D1 subfamily includes the D1 and D5 receptors, whereas the D2 subfamily comprises the D2, D3, and D4 receptors. Systemic administration of a selective D1 receptor agonist induces behavioral arousal, together with an increase of W and a reduction of slow wave sleep (SWS) and REM sleep (REMS). Systemic injection of a DA D2 receptor agonist induces biphasic effects, such that low doses reduce W and increase SWS and REMS (predominant activation of the D2 autoreceptor), whereas large doses induce the opposite effect (predominant facilitation of the D2 postsynaptic receptor). Compounds with DA D1 or D2 receptor blocking properties augment non-REMS and reduce W. Preliminary findings tend to indicate that the administration of a DA D3-preferring agonist induces somnolence and sleep in laboratory animals and man. DA neurons in the VTA and the SNc do not change their mean firing rate across the sleep-wake cycle. It has been proposed that DA cells in the midbrain show a change in temporal pattern rather than firing rate during the sleep-wake cycle. The available evidence tends to indicate that during W there occurs an increase of burst firing activity of DA neurons, and an enhanced release of DA in the VTA, the nucleus accumbens (NAc), and a number of forebrain structures. A series of structures relevant for the regulation of the behavioral state, including the DRN, LDT/PPT, LC, and LH, could be partly responsible for the changes in the temporal pattern of activity of DA neurons. The involvement of dopamine in the modulation of sleep and waking Jaime Monti Daniel Monti doi:10.1016/j.smrv.2006.08.003 Sleep Medicine Reviews, Vol. 11, No. 2. (April 2007), pp. 113-133. 2008-03-06T11:56:23-00:00 Sleep Medicine Reviews 11 2 113 133 d1-receptor d2-receptor dopamine review sleep http://www.citeulike.org/user/awooga/article/2478303 <i>Journal of Neurochemistry, Vol. 68, No. 2. (1997), pp. 691-697.</i><br /><br />Abstract: Auditory cortex has been shown to be a site of widespread neuronal learning processes even in the context of simple auditory conditioning behavior. In view of their presumed role in determining behavioral and motivational relevance of incoming information we investigated whether the dopaminergic and serotonergic systems are involved in auditory cortex learning. Using a chronic brain microdialysis technique over 4 days, samples from auditory cortex were obtained before, during, and after daily footshock avoidance training simultaneously from trained gerbils and passive control animals or pseudotrained animals. Because of detection limits of dopamine and serotonin in auditory cortex, the response profiles of extracellular homovanillic acid as the metabolite of the dopaminergic system and of 5-hydroxyindoleacetic acid as the metabolite of the serotonergic system were determined from consecutive dialysis samples each day. The response of the dopaminergic system appeared to reflect the initial formation of the behaviorally relevant association exclusively during the first training day, whereas the serotonergic response appeared to correlate with the stress level of animals. Dopaminergic and Serotonergic Neurotransmission Systems Are Differentially Involved in Auditory Cortex Learning: A Long-Term Microdialysis Study of Metabolites Holger Stark Henning Scheich doi:10.1046/j.1471-4159.1997.68020691.x Journal of Neurochemistry, Vol. 68, No. 2. (1997), pp. 691-697. 2008-03-06T11:06:34-00:00 Journal of Neurochemistry 68 2 691 697 auditory cortex dopamine microdialysis neuromodulation serotonin http://www.citeulike.org/user/awooga/article/2465189 <i>J Psychopharmacol, Vol. 21, No. 1. (1 January 2007), pp. 50-64.</i><br /><br />Hallucinogenic psilocybin is known to alter the subjective experience of time. However, there is no study that systematically investigated objective measures of time perception under psilocybin. Therefore, we studied dose-dependent effects of the serotonin (5-HT)2A/1A receptor agonist psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) on temporal processing, employing tasks of temporal reproduction, sensorimotor synchronization and tapping tempo. To control for cognitive and subjective changes, we assessed spatial working memory and conscious experience. Twelve healthy human volunteers were tested under placebo, medium (115microg/kg), and high (250microg/kg) dose conditions, in a double-blind experimental design. Psilocybin was found to significantly impair subjects' ability to (1) reproduce interval durations longer than 2.5 sec, (2) to synchronize to inter-beat intervals longer than 2 sec and (3) caused subjects to be slower in their preferred tapping rate. These objective effects on timing performance were accompanied by working-memory deficits and subjective changes in conscious state, namely increased reports of depersonalization' and derealization' phenomena including disturbances in subjective time sense.' Our study is the first to systematically assess the impact of psilocybin on timing performance on standardized measures of temporal processing. Results indicate that the serotonin system is selectively involved in duration processing of intervals longer than 2 to 3 seconds and in the voluntary control of the speed of movement. We speculate that psilocybin's selective disruption of longer intervals is likely to be a product of interactions with cognitive dimensions of temporal processing -presumably via 5-HT2A receptor stimulation. 10.1177/0269881106065859 Effects of psilocybin on time perception and temporal control of behaviour in humans Marc Wittmann Olivia Carter Felix Hasler Rael Cahn Ulrike Grimberg Philipp Spring Daniel Hell Hans Flohr Franz Vollenweider doi:10.1177/0269881106065859 J Psychopharmacol, Vol. 21, No. 1. (1 January 2007), pp. 50-64. 2008-03-04T15:54:25-00:00 J Psychopharmacol 21 1 50 64 behavioural-test magic-mushrooms time working-memory http://www.citeulike.org/user/awooga/article/2464926 <i>J. Cogn. Neurosci., Vol. 17, No. 10. (1 October 2005), 1497.</i><br /><br />Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were tested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 microg/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggesting a primary involvement of the 5-HT1A receptor in the observed deficit. Based on physiological and pharmacological data, we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed. Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors Olivia Carter David Burr John Pettigrew Guy Wallis Felix Hasler Franz Vollenweider J. Cogn. Neurosci., Vol. 17, No. 10. (1 October 2005), 1497. 2008-03-04T14:07:41-00:00 J. Cogn. Neurosci. 17 10 1497 5ht1a 5ht2a attention hallucinagenics magic-mushrooms serotonin working-memory http://www.citeulike.org/user/awooga/article/2460967 <i>Annals of the New York Academy of Sciences, Vol. 877, No. 1. (1999), pp. 339-367.</i><br /><br />ABSTRACT: The medial septum, diagonal bands, ventral pallidum, substantia innominata, globus pallidus, and internal capsule contain a heterogeneous population of neurons, including cholinergic and noncholinergic (mostly GABA containing), corticopetal projection neurons, and interneurons. This highly complex brain region, which constitutes a significant part of the basal forebrain has been implicated in attention, motivation, learning, as well as in a number of neuropsychiatric disorders, such as Alzheimer's disease, Parkinson's disease, and schizophrenia. Part of the difficulty in understanding the functions of the basal forebrain, as well as the aberrant information-processing characteristics of these disease states lies in the fact that the organizational principles of this brain area remained largely elusive. On the basis of new anatomical data, it is proposed that a large part of the basal forebrain corticopetal system be organized into longitudinal bands. Considering the topographic organization of cortical afferents to different divisions of the prefrontal cortex and a similar topographic projection of these prefrontal areas to basal forebrain regions, it is suggested that several functionally segregated cortico-prefronto-basal forebrain-cortical circuits exist. It is envisaged that such specific "triangular" circuits could amplify selective attentional processing in posterior sensory cortical areas. The Basal Forebrain Corticopetal System Revisited L Zaborszky K Pang J Somogyi Z Nadasdy I Kallo doi:10.1111/j.1749-6632.1999.tb09276.x Annals of the New York Academy of Sciences, Vol. 877, No. 1. (1999), pp. 339-367. 2008-03-03T14:36:41-00:00 Annals of the New York Academy of Sciences 877 1 339 367 acetylcholine basal-forebrain cortex neuromodulation review http://www.citeulike.org/user/awooga/article/2460963 <i>Neuroscience, Vol. 84, No. 2. (11 February 1998), pp. 331-359.</i><br /><br />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. Cholinergic neurons and terminal fields revealed by immunohistochemistry for the vesicular acetylcholine transporter. I. Central nervous system Schafer LE Eiden E Weihe doi:10.1016/S0306-4522(97)00516-2 Neuroscience, Vol. 84, No. 2. (11 February 1998), pp. 331-359. 2008-03-03T14:34:45-00:00 Neuroscience 84 2 331 359 no-tag http://www.citeulike.org/user/awooga/article/2460944 <i>Progress in Neurobiology, Vol. 47, No. 2. (October 1995), pp. 105-133.</i><br /><br />This review describes the role of the pedunculopontine nucleus (PPN) in various functions, including sleep-wake mechanisms, arousal, locomotion and in several pathological conditions. Special emphasis is placed on the auditory input to the PPN and the possible role of this nucleus in the manifestation of the P1 middle latency auditory evoked response. The importance of these considerations is evident because the PPN is part of the cholinergic arm of the reticular activating system. As such, the auditory input to this region may modulate the level of arousal of the CNS and, consequently, abnormalities in the processing of this input can be expected to have serious consequences on the level of excitability of the CNS. The involvement of the PPN in such disorders as schizophrenia, anxiety disorder and narcolepsy is discussed. The pedunculopontine nucleus--Auditory input, arousal and pathophysiology NB Reese E Garcia-Rill RD Skinner doi:10.1016/0301-0082(95)00023-O Progress in Neurobiology, Vol. 47, No. 2. (October 1995), pp. 105-133. 2008-03-03T14:24:41-00:00 Progress in Neurobiology 47 2 105 133 acetylcholine arousal auditory neuromodulation pptn sleep http://www.citeulike.org/user/awooga/article/2447209 <i>Science, Vol. 319, No. 5867. (29 February 2008), pp. 1264-1267.</i><br /><br />Current theories hypothesize that dopamine neuronal firing encodes reward prediction errors. Although studies in nonhuman species provide direct support for this theory, functional magnetic resonance imaging (fMRI) studies in humans have focused on brain areas targeted by dopamine neurons [ventral striatum (VStr)] rather than on brainstem dopaminergic nuclei [ventral tegmental area (VTA) and substantia nigra]. We used fMRI tailored to directly image the brainstem. When primary rewards were used in an experiment, the VTA blood oxygen leveldependent (BOLD) response reflected a positive reward prediction error, whereas the VStr encoded positive and negative reward prediction errors. When monetary gains and losses were used, VTA BOLD responses reflected positive reward prediction errors modulated by the probability of winning. We detected no significant VTA BOLD response to nonrewarding events. 10.1126/science.1150605 BOLD Responses Reflecting Dopaminergic Signals in the Human Ventral Tegmental Area Kimberlee D'Ardenne Samuel Mcclure Leigh Nystrom Jonathan Cohen doi:10.1126/science.1150605 Science, Vol. 319, No. 5867. (29 February 2008), pp. 1264-1267. 2008-02-29T10:21:12-00:00 Science 319 5867 1264 1267 dopamine fmri striatum vta http://www.citeulike.org/user/awooga/article/2448219 <i>J. Neurosci., Vol. 12, No. 10. (1 October 1992), pp. 4037-4044.</i> Neurochemical afferents controlling the activity of serotonergic neurons in the dorsal raphe nucleus: microiontophoretic studies in the awake cat ES Levine BL Jacobs J. Neurosci., Vol. 12, No. 10. (1 October 1992), pp. 4037-4044. 2008-02-29T17:08:59-00:00 J. Neurosci. 12 10 4037 4044 cortex gabaergic noradrenaline raphe-nucleus serotonin