- Email: [email protected]
Neural network challenge solved
138
News & Comment
TRENDS in Neurosciences Vol.24 No.3 March 2001
In Brief
Imaging the sleeping brain In the December issue of Neuron, a research group at the Institute of Neurology, UK, has reported that a human sleeping brain can be influenced by external auditory stimuli in a stimulus-specific manner. Using fMRI images, researchers found that saying the participant’s name evoked a greater activation compared with a generic beep in orbitofrontal regions and the amygdaloid complex in both awake and sleep states. Amazingly, the activation in response to the name stimulus was greatest during nonREM sleep, when these regions are normally deactivated. This suggests that during sleep, important external information can reactivate neural circuits to a higher level compared with that achieved when awake. The implications of this study extend beyond sleep research and auditory processing to touch upon issues of consciousness in normal and altered states.
instituted so President-elect George W. Bush set a new budget. When disagreements had delayed the approval past election day, Congress passed several temporary funding bills to sustain operations in the interim. Under the new budget, both the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health are expected to receive over a billion dollars each. Additionally, $47 million dollars was requested to construct a new National Neuroscience Research Center that would foster collaboration among the different NIH institutes that support neuroscience research. This center would receive a total of $73 million over two years.
might also have therapeutic potential because other Na+ channel blockers have been used as painkillers and anti-epileptics.
New neurotoxin reported in blue-green algae
In a retrospective, case-control study reported in the December 20 J. Am. Med. Assoc. no association was found between cellular phone use and temporal lobe tumors. Furthermore, in patients with brain cancers, there was no association between handedness and tumor location. Using phone bills and questionnaires to interview individuals with and without brain cancer about their cellular phone use between 1994 and 1998, no significant differences were found between the two groups regarding either the number of months the phone was used or the number of hours of use each month. This is good news not only for cellular phone users, but also the cellular phone industry, which is facing billions of dollars in lawsuits. The study is limited, however, to adults using analog services for an average of only two to three hours a month for a period of two to three years. Longer-term health effects in more frequent and younger users still needs to be investigated.
Drosophila axonal pathfinding Researchers have uncovered intricate axonal pathfinding mechanisms involving attraction, repulsion, and concentration gradients in developing fruit flies. Proteins called netrins initally attract the axons toward the midline, but after the axons cross the midline they begin to express a receptor protein, roundabout (or robo) for the repellant protein, ‘slit.’ This insures axons do not cross back over the midline before finding appropriate axon bundles to travel with. Now, with the report of two new additional receptors, robo2 and robo3, researchers show that the more robo receptor types the axon expresses, the further from the midline it travels. Axons expressing only robo1 choose a path very near and parallel to the center line, whereas axons expressing all three receptors travel the furthest away to areas of lower slit concentration. The complete studies were published by two separate research teams in four papers in the December issues of Cell and Neuron.
NIH budget approved In December, the United States Congress approved a 14.2% increase for the National Institutes of Health (NIH). This raises the NIH budget to $20.3 billion. The approval abolished concerns that a freeze would be
A neurotoxin that is novel in structure and potency and which acts at voltage-gated Na+ channels, was reported at the 2000 International Chemical Congress of Pacific Basin Societies, which is comprised of the national chemical societies in the United States, Australia, Canada, Japan and New Zealand. The toxin was extracted from the marine cyanobacteria Lyngbya majuscula, the blue-green algae commonly known as ‘pond scum,’ in the Caribbean island of Curacao. It has been named ‘kalkitoxin’ in honor of the islands Kalki Bay in which it was found. The lethal toxin targets Na+ channels in brine shrimp and prevents nerves cells from generating and propagating action potentials. Known toxins have been instrumental in teaching neuroscientists how these channels work and kalkitoxin, which is structurally unrelated to these toxins, may reveal additional insights. The compound
No link between cellular phone use and brain cancer
Neural network challenge solved In a novel attempt to stimulate neuroscientists to think about how the brain handles pattern-recognition tasks, researchers at Princeton and New York Universities developed an intellectual contest. They created an artificial organism based on simple properties of brain function and encouraged scientists to investigate how this ‘silicon mouse’ recognizes the word ‘one.’ The challenge was to deduce the principles operating this network from ‘experimental’ observations, or reconstruct
http://tins.trends.com 0166-2236/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
News & Comment
TRENDS in Neurosciences Vol.24 No.3 March 2001
139
a system that recognized the word using the same neuron-like elements. The contest, which was announced in September, was won by physicists at Cambridge University, UK. Only one other person, a California Institute of Technology graduate student, answered the problem by the December deadline. To test your abilities, you can visit the website (http://shadrach.cns.nyu.edu/~carlos/ Organism/), which now also contains the solution. The novel principles underlying the system are published in December 18 issue of Proc. Natl Acad. Sci. U. S. A.
the specific impairments in learning and memory. Human safety trials for the vaccine have already been successfully completed. Whether the Aβ plaques actually cause dementia in people is still debated among researchers, but these promising results nicely coincide with results from three other groups of researchers who are honing in on possibly two separate Alzheimer’s genes located on Chromosome 10 that might also regulate Aβ levels.
European countries, consumer’s fears increase and import bans increase. BSE has been linked to the fatal Creutzfeldt-Jakob disease (CJD) in humans and is thought to be caused by self-replicating proteins called prions. Reforms, prohibiting animal feed made from possibly infected animal parts, were instituted by the European Union (EU) after a rash of BSE cases were reported in Britain. New cases in the past year, especially outside Britain, and studies like one included in a December Nature have suggest that infection rates may have been underestimated. The EU Food Safety commission is considering additional precautions. Investigations by agricultural and health experts in the USA indicate an epidemic there is unlikely, but lessons from the situation in Europe are being recognized.
BSE scare escalates
Advancing Alzheimer’s In a collection of papers published in the December 21 issue of Nature, researchers, using a transgenic mouse model of Alzheimer’s disease, have shown that accumulation of amyloid-beta (Aβ) protein deposits correlate with cognitive decline. Furthermore, a vaccination with Aβ significantly reduces both the deposits and
This months ‘In Brief’ articles were written by Lianna Orlando ([email protected])
As more cases of Bovine spongiform encephalopathy (BSE) are identified in England, Germany, France, Spain and other
Letters
Kainate receptors keep the excitement high In a recent and interesting review of the activities of kainate, Ben-Ari and Cossart1 emphasize that the epileptic effect of kainate reflects the high density of kainate receptors that are present in CA3 pyramidal cells rather than the depression of GABA transmission in the hippocampus. Furthermore, they explain that kainate might have a paradoxical anti-epileptic effect because of the depolarization it induces in hippocampal GABA interneurons that, in turn, leads to a ‘massive increase in tonic inhibitory drive’ of pyramidal neurons. There is no question that the selective activation of GABA interneurons might act to prevent seizures. However, this is irrespective of the receptor used for that purpose. Therefore, considering the overall effects of kainate on in vivo tissue excitability when locally applied2, I think it is premature to consider kainate as anti-epileptogenic. A clear lesson emerges when examining the literature on kainate: the acute and chronic effects of kainate should be
considered separately. It is well known that systemic injections of kainate induce electroencephalographic and behavioral seizures, followed by neuronal loss1. However, the multiple actions of kainate at the cellular level make it difficult to assess what activities are responsible for its chronic action. Indeed, it seems most appropriate to consider that epilepsy and neuronal degeneration are not the consequence of a single effect of kainate, the former originating from a quick and overall imbalance in excitability. For all those who have studied hippocampal excitability, it seems trivial that any treatment that involves a decrease of GABA inhibition should convey with it the generation of seizures. Both, in vivo and in vitro studies have systematically shown that independent of the substance used, depression of GABA inhibition results in epileptic seizures (see Ref. 3 and references therein). In their pioneering paper3, Fisher and Alger wondered whether kainate might induce epileptic activity in the vertebrate CNS by direct excitation and not through disinhibition. Although this still remains unresolved, a common feature shown by kainate and many other epileptogenic substances (e.g. picrotoxin, penicillin, bicuculline) is that they decrease inhibition.
In considering the acute effects of kainate, it cannot be denied that the CA3 area is more sensitive than CA1 and that it acts as a pacemaker for burst discharges in the hippocampus4. But rejecting a role for CA1 in epilepsy would be similar to ignoring the hippocampal theta rhythm as a result of the fact that this activity is no longer spontaneously present in hippocampal slices5. Therefore, seizures must be the result of a complex interaction of many components, some of which are absent in the isolated CA1. In support of this, Fisher and Alger3 reported that kainate-induced bursting activity in CA3 preceded that in CA1, albeit only for a short period of time. Afterwards, shocks to the stratum radiatum (the entry to CA1) remained effective in eliciting CA1 cell bursting (see Fig. 1 in Ref. 3). Additionally, they showed that there is a good correlation between kainate-induced IPSP depression and the onset of burst-firing in response to this synaptic stimulation, and they concluded that depression of synaptic inhibition by kainate was the major component of this bursting activity. Indeed, in slices in which CA1 was surgically isolated from CA3, low doses of bicuculline lead to evoked bursts of activity resembling an epileptic pattern
http://tins.trends.com 0166-2236/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
News & Comment
TRENDS in Neurosciences Vol.24 No.3 March 2001
In Brief
Imaging the sleeping brain In the December issue of Neuron, a research group at the Institute of Neurology, UK, has reported that a human sleeping brain can be influenced by external auditory stimuli in a stimulus-specific manner. Using fMRI images, researchers found that saying the participant’s name evoked a greater activation compared with a generic beep in orbitofrontal regions and the amygdaloid complex in both awake and sleep states. Amazingly, the activation in response to the name stimulus was greatest during nonREM sleep, when these regions are normally deactivated. This suggests that during sleep, important external information can reactivate neural circuits to a higher level compared with that achieved when awake. The implications of this study extend beyond sleep research and auditory processing to touch upon issues of consciousness in normal and altered states.
instituted so President-elect George W. Bush set a new budget. When disagreements had delayed the approval past election day, Congress passed several temporary funding bills to sustain operations in the interim. Under the new budget, both the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health are expected to receive over a billion dollars each. Additionally, $47 million dollars was requested to construct a new National Neuroscience Research Center that would foster collaboration among the different NIH institutes that support neuroscience research. This center would receive a total of $73 million over two years.
might also have therapeutic potential because other Na+ channel blockers have been used as painkillers and anti-epileptics.
New neurotoxin reported in blue-green algae
In a retrospective, case-control study reported in the December 20 J. Am. Med. Assoc. no association was found between cellular phone use and temporal lobe tumors. Furthermore, in patients with brain cancers, there was no association between handedness and tumor location. Using phone bills and questionnaires to interview individuals with and without brain cancer about their cellular phone use between 1994 and 1998, no significant differences were found between the two groups regarding either the number of months the phone was used or the number of hours of use each month. This is good news not only for cellular phone users, but also the cellular phone industry, which is facing billions of dollars in lawsuits. The study is limited, however, to adults using analog services for an average of only two to three hours a month for a period of two to three years. Longer-term health effects in more frequent and younger users still needs to be investigated.
Drosophila axonal pathfinding Researchers have uncovered intricate axonal pathfinding mechanisms involving attraction, repulsion, and concentration gradients in developing fruit flies. Proteins called netrins initally attract the axons toward the midline, but after the axons cross the midline they begin to express a receptor protein, roundabout (or robo) for the repellant protein, ‘slit.’ This insures axons do not cross back over the midline before finding appropriate axon bundles to travel with. Now, with the report of two new additional receptors, robo2 and robo3, researchers show that the more robo receptor types the axon expresses, the further from the midline it travels. Axons expressing only robo1 choose a path very near and parallel to the center line, whereas axons expressing all three receptors travel the furthest away to areas of lower slit concentration. The complete studies were published by two separate research teams in four papers in the December issues of Cell and Neuron.
NIH budget approved In December, the United States Congress approved a 14.2% increase for the National Institutes of Health (NIH). This raises the NIH budget to $20.3 billion. The approval abolished concerns that a freeze would be
A neurotoxin that is novel in structure and potency and which acts at voltage-gated Na+ channels, was reported at the 2000 International Chemical Congress of Pacific Basin Societies, which is comprised of the national chemical societies in the United States, Australia, Canada, Japan and New Zealand. The toxin was extracted from the marine cyanobacteria Lyngbya majuscula, the blue-green algae commonly known as ‘pond scum,’ in the Caribbean island of Curacao. It has been named ‘kalkitoxin’ in honor of the islands Kalki Bay in which it was found. The lethal toxin targets Na+ channels in brine shrimp and prevents nerves cells from generating and propagating action potentials. Known toxins have been instrumental in teaching neuroscientists how these channels work and kalkitoxin, which is structurally unrelated to these toxins, may reveal additional insights. The compound
No link between cellular phone use and brain cancer
Neural network challenge solved In a novel attempt to stimulate neuroscientists to think about how the brain handles pattern-recognition tasks, researchers at Princeton and New York Universities developed an intellectual contest. They created an artificial organism based on simple properties of brain function and encouraged scientists to investigate how this ‘silicon mouse’ recognizes the word ‘one.’ The challenge was to deduce the principles operating this network from ‘experimental’ observations, or reconstruct
http://tins.trends.com 0166-2236/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
News & Comment
TRENDS in Neurosciences Vol.24 No.3 March 2001
139
a system that recognized the word using the same neuron-like elements. The contest, which was announced in September, was won by physicists at Cambridge University, UK. Only one other person, a California Institute of Technology graduate student, answered the problem by the December deadline. To test your abilities, you can visit the website (http://shadrach.cns.nyu.edu/~carlos/ Organism/), which now also contains the solution. The novel principles underlying the system are published in December 18 issue of Proc. Natl Acad. Sci. U. S. A.
the specific impairments in learning and memory. Human safety trials for the vaccine have already been successfully completed. Whether the Aβ plaques actually cause dementia in people is still debated among researchers, but these promising results nicely coincide with results from three other groups of researchers who are honing in on possibly two separate Alzheimer’s genes located on Chromosome 10 that might also regulate Aβ levels.
European countries, consumer’s fears increase and import bans increase. BSE has been linked to the fatal Creutzfeldt-Jakob disease (CJD) in humans and is thought to be caused by self-replicating proteins called prions. Reforms, prohibiting animal feed made from possibly infected animal parts, were instituted by the European Union (EU) after a rash of BSE cases were reported in Britain. New cases in the past year, especially outside Britain, and studies like one included in a December Nature have suggest that infection rates may have been underestimated. The EU Food Safety commission is considering additional precautions. Investigations by agricultural and health experts in the USA indicate an epidemic there is unlikely, but lessons from the situation in Europe are being recognized.
BSE scare escalates
Advancing Alzheimer’s In a collection of papers published in the December 21 issue of Nature, researchers, using a transgenic mouse model of Alzheimer’s disease, have shown that accumulation of amyloid-beta (Aβ) protein deposits correlate with cognitive decline. Furthermore, a vaccination with Aβ significantly reduces both the deposits and
This months ‘In Brief’ articles were written by Lianna Orlando ([email protected])
As more cases of Bovine spongiform encephalopathy (BSE) are identified in England, Germany, France, Spain and other
Letters
Kainate receptors keep the excitement high In a recent and interesting review of the activities of kainate, Ben-Ari and Cossart1 emphasize that the epileptic effect of kainate reflects the high density of kainate receptors that are present in CA3 pyramidal cells rather than the depression of GABA transmission in the hippocampus. Furthermore, they explain that kainate might have a paradoxical anti-epileptic effect because of the depolarization it induces in hippocampal GABA interneurons that, in turn, leads to a ‘massive increase in tonic inhibitory drive’ of pyramidal neurons. There is no question that the selective activation of GABA interneurons might act to prevent seizures. However, this is irrespective of the receptor used for that purpose. Therefore, considering the overall effects of kainate on in vivo tissue excitability when locally applied2, I think it is premature to consider kainate as anti-epileptogenic. A clear lesson emerges when examining the literature on kainate: the acute and chronic effects of kainate should be
considered separately. It is well known that systemic injections of kainate induce electroencephalographic and behavioral seizures, followed by neuronal loss1. However, the multiple actions of kainate at the cellular level make it difficult to assess what activities are responsible for its chronic action. Indeed, it seems most appropriate to consider that epilepsy and neuronal degeneration are not the consequence of a single effect of kainate, the former originating from a quick and overall imbalance in excitability. For all those who have studied hippocampal excitability, it seems trivial that any treatment that involves a decrease of GABA inhibition should convey with it the generation of seizures. Both, in vivo and in vitro studies have systematically shown that independent of the substance used, depression of GABA inhibition results in epileptic seizures (see Ref. 3 and references therein). In their pioneering paper3, Fisher and Alger wondered whether kainate might induce epileptic activity in the vertebrate CNS by direct excitation and not through disinhibition. Although this still remains unresolved, a common feature shown by kainate and many other epileptogenic substances (e.g. picrotoxin, penicillin, bicuculline) is that they decrease inhibition.
In considering the acute effects of kainate, it cannot be denied that the CA3 area is more sensitive than CA1 and that it acts as a pacemaker for burst discharges in the hippocampus4. But rejecting a role for CA1 in epilepsy would be similar to ignoring the hippocampal theta rhythm as a result of the fact that this activity is no longer spontaneously present in hippocampal slices5. Therefore, seizures must be the result of a complex interaction of many components, some of which are absent in the isolated CA1. In support of this, Fisher and Alger3 reported that kainate-induced bursting activity in CA3 preceded that in CA1, albeit only for a short period of time. Afterwards, shocks to the stratum radiatum (the entry to CA1) remained effective in eliciting CA1 cell bursting (see Fig. 1 in Ref. 3). Additionally, they showed that there is a good correlation between kainate-induced IPSP depression and the onset of burst-firing in response to this synaptic stimulation, and they concluded that depression of synaptic inhibition by kainate was the major component of this bursting activity. Indeed, in slices in which CA1 was surgically isolated from CA3, low doses of bicuculline lead to evoked bursts of activity resembling an epileptic pattern
http://tins.trends.com 0166-2236/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.