- Email: [email protected]
Synaptic transmission on the Barrier Reef
12
Research Update
TRENDS in Neurosciences Vol.25 No.1 January 2002
Meeting Report
Synaptic transmission on the Barrier Reef Stephen J. Redman and Bruce Walmsley The IUPS Satellite Symposium on Synaptic Transmission in the Central Nervous System was held on Heron Island, Australia from 3–6 September 2001.
A gathering of many leading neuroscientists was held in September in the relaxed and beautiful setting of Heron Island, one of the smallest islands of the Great Barrier Reef, Australia. The meeting was organized by Steve Redman and Bruce Walmsley from the Australian National University, and by Bert Sakmann, who opened the symposium. Each of the four days of the meeting was organized around a general theme, progressing from the most fundamental mechanisms of synaptic transmission on the first day, to integrative properties of neurones and neural networks on the final day. Transmitter release mechanisms
Meyer Jackson (Madison) set the scene by presenting evidence on the kiss-and-run versus vesicle fusion hypotheses, with direct measurement of transmitter release using capacitance measurements and amperometry. Richard Tsien (Stanford) analysed electron-micrographs of photo-converted FM dyes and proposed that there are too few vesicles in the conventional recycling pool to account for measured levels of quantal transmitter release. He proposed that many vesicles might be retained via a kiss-and-run mechanism and subsequently undergo rapid refilling with transmitter. Studies of a giant synaptic connection, the calyx of Held, were the focus of three presentations. Bert Sakmann (Heidelberg) showed from electron-microscopy that the calyx of Held contains in the order of 600 active zones, but that each active zone exhibits only one or two morphologically docked vesicles. Ian Forsythe (Leicester) showed that mitochondria in the terminal play a significant role in determining presynaptic cytoplasmic Ca2+ levels, especially during and following high-frequency trains of impulses. Erwin Neher (Göttingen) presented simultaneous pre- and postsynaptic recordings at the calyx, and proposed that http://tins.trends.com
Heron Island Resort, website http://www.heronisland.com
there are two pools of vesicles, one with high and one with low release probabilities. Two other talks took advantage of large synaptic connections. The intrinsic differences between tonic and phasic synapses were explored by Harold Atwood (Toronto) to refute some common preconceptions of the role of Ca2+-channel density and Ca2+ entry as determinants of release probability. Presynaptic patch-electrode recordings featured again at the small but numerous boutons of cerebellar basket cells, allowing Brian Robertson (London) to directly demonstrate multiple K+-channel types in these basket cell terminals. At the molecular level, Ed Chapman (Madison) presented evidence on the difference between the two Ca2+-binding domains of synaptotagmin, and Sandra Bajjalieh (Seattle) proposed that the synaptic vesicle protein, SV2, might serve to modulate synaptotagmin binding and clustering. One clear take-away message is that vesicles do not have homogeneous properties, and that there is a big gap in reconciling morphology in the terminal with function. Modulation of transmission
Mike Bennett (New York) presented evidence for the rapid insertion of NMDA receptors into membrane, whereas Rosemarie Grantyn (Berlin) showed that
there are complex interactions between GABA receptors, glycine receptors and gephyrin during development. Bob Zucker (Berkeley) and Julie Kauer (Providence) stressed the role of Ca2+ in activating pathways involving second messengers, such as cAMP, in long-term changes of synaptic strength. Guosong Liu (Boston) proposed that differences in the time course of glutamate in the synaptic cleft might modulate synaptic strength and underlie the observation of silent AMPA synapses, and Angus Silver (London) implicated transmitter spillover between synapses in the synaptic cleft at cerebellar mossy fiber terminals. The final session of day two concerned the role of intracellular Ca2+. Tim Bliss (London), Bill Ross (New York), Pankaj Sah (Canberra), Mike Friedlander (Birmingham) and Christian Stricker (Zurich) presented evidence supporting a role for intracellular Ca2+ stores in a range of synaptic processes from LTP to spontaneous transmitter release. Learning about ways in which release can be modulated has the potential to provide more insights into release mechanisms per se, and the more one learns about the modulatory potential in release mechanisms, the more it becomes apparent how much potential plasticity resides in the nerve terminal.
0166-2236/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S0166-2236(00)02066-X
Research Update
Integrative properties of dendrites
Greg Stuart (Canberra), Dan Johnson (Houston), Michael Hausser (London), Mathew Larkum (Heidelberg), Jeff Magee (New Orleans) and Indira Ramon (Chicago) presented data on backpropagation of action potentials, summation of EPSPs and IPSPs, non-linearities involved in detecting coincident inputs at widely separated regions of the dendritic tree, persistent Na+ currents and mechanisms for boosting the strength of distal synaptic inputs. Larry Abbott’s (Brandeis) talk was relevant to this point, as his modeling demonstrated the way that synaptic noise could change the gain of the firing frequency–current relationship in a simple neurone. The transmission of information from synapse to output-spike train also came in for some theoretical attention from Idan Segev (Jerusalem), who introduced the concept of mutual information measures. Inhibitory synapses were also discussed by both Lea Ziskind-Conhaim (Madison) and Albert Berger (Seattle) reporting on spontaneous mIPSCs in spinal and brainstem motoneurones. The mIPSCs could be either glycinergic, GABAergic or a combination of both types. These talks made it clear that the list of computational complexities that a neurone can perform continues to grow, but the discussion often
TRENDS in Neurosciences Vol.25 No.1 January 2002
questioned the physiological relevance of some of these phenomena if they were superimposed upon a membrane potential resulting from a continuous barrage of synaptic inputs rather than at rest. Shaping of network and behavioral responses by synaptic and neuronal properties
One of Don Faber’s (New York) contributions was to show that the goldfish escape response slowed with a drop in temperature and this was paralleled by an increase in the integration time constant of the Mauthner cell. Jeff Smith (Bethesda) described the essential properties of the pre-Botzinger neurones and their connectivity that gives rise to inspiratory rhythm. These neurons must possess a persistent Na+ current and a leak current, and the properties of both currents must be graded throughout the network. Rowland Taylor (Canberra) showed how directional selectivity of retinal ganglion cells was determined by temporal interactions of EPSPs and IPSPs within the ganglion cells. The debate here is whether these mechanisms account for all directional selectivity or whether some presynaptic interactions are also involved. Bill Spain (Seattle) showed how sound localization is signaled by neurones in the nucleus laminaris acting as coincidence detectors for the inputs from both ears to
13
detect inter-aural delays. Yossi Yarom (Jerusalem) discussed synchronized oscillations in membrane potential in neurons in the inferior olive – how their frequency can be altered by synaptic input and how weak electrical coupling preserves synchrony. Cautionary issues of non-uniqueness in ascribing dynamical changes in network behavior to changes in synaptic transmission or to changes in neuronal properties were illustrated by David McCormick (New Haven), using recordings from visual neurons in vivo and in vitro. The meeting ended with Matt Wilson (MIT) relating molecular deletion of NR1 subunit in CA3 hippocampus to spatial-memory performance. NMDA receptors in CA3 are not required for acquisition of spatial reference memory but are required for pattern completion when the number of spatial cues is reduced. The message from this day was that real progress is being made in understanding those networks for which the physiological role is tightly defined. Stephen J. Redman* Bruce Walmsley Division of Neuroscience, John Curtin School of Medical Research, Australian National University, GPO Box 334, Canberra, ACT 2601, Australia. *e-mail: [email protected]
Buenos Aires: Tango makes way for science Branwen Morgan and Marcelo Rubinstein The Joint International and American Neurochemistry Society Meeting was held, in collaboration with SAN (Sociedad Argentina de Neuroquímica), in Buenos Aires, Argentina from 26–31 August 2001.
Stem cells
In August of 2001, 850 neurochemists descended upon Buenos Aires, a city with a passion for Tango. ‘Hot’ science was presented on a wide variety of topics, such as brain gene regulation in cellular life and death processes (including neurodegenerative disease), central nervous system (CNS) regeneration by gene therapy and stem cell transplantation, signal transduction and neuronal plasticity. http://tins.trends.com
Even in the regions of the brain where they reside, neural stem cells are in extremely low abundance, making it difficult to study them. Previously, neural stem cells have been obtained at no more than 5% purity. Now Rod Rietze (Melbourne, Australia) and colleagues have purified a population of brain cells from an adult mouse brain to the point where 80% of the cells have properties of in vitro stem cells [1]. The researchers also studied the differentiation of these neural stem cells, when co-cultured with a muscle cell line, into muscle cells. The signals that allow cell differentiation to take place will obviously feature highly in subsequent investigations. A powerful complementary approach to solving the mystery of the
molecular basis of stem cell plasticity was presented by Annika Dahl (Goteburg, Sweden). Dahl is applying a special type of mass spectrometry (MALDI-TOF MS) to identify peptides and proteins secreted from rat stem cells. In addition to detecting cystatin c, a known protein secreted by stem cells in vitro, she has identified two other proteins with this method that are being investigated for their role in stem cell plasticity. Some valuable clues are also being found from expression profiles of stem cells obtained by microarray analysis. Brain and blood have been turned into each other, like water into wine. Karen Chandross presented elegant work, published last December, demonstrating that bone marrow-derived cells from the
0166-2236/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S0166-2236(00)02039-7
Research Update
TRENDS in Neurosciences Vol.25 No.1 January 2002
Meeting Report
Synaptic transmission on the Barrier Reef Stephen J. Redman and Bruce Walmsley The IUPS Satellite Symposium on Synaptic Transmission in the Central Nervous System was held on Heron Island, Australia from 3–6 September 2001.
A gathering of many leading neuroscientists was held in September in the relaxed and beautiful setting of Heron Island, one of the smallest islands of the Great Barrier Reef, Australia. The meeting was organized by Steve Redman and Bruce Walmsley from the Australian National University, and by Bert Sakmann, who opened the symposium. Each of the four days of the meeting was organized around a general theme, progressing from the most fundamental mechanisms of synaptic transmission on the first day, to integrative properties of neurones and neural networks on the final day. Transmitter release mechanisms
Meyer Jackson (Madison) set the scene by presenting evidence on the kiss-and-run versus vesicle fusion hypotheses, with direct measurement of transmitter release using capacitance measurements and amperometry. Richard Tsien (Stanford) analysed electron-micrographs of photo-converted FM dyes and proposed that there are too few vesicles in the conventional recycling pool to account for measured levels of quantal transmitter release. He proposed that many vesicles might be retained via a kiss-and-run mechanism and subsequently undergo rapid refilling with transmitter. Studies of a giant synaptic connection, the calyx of Held, were the focus of three presentations. Bert Sakmann (Heidelberg) showed from electron-microscopy that the calyx of Held contains in the order of 600 active zones, but that each active zone exhibits only one or two morphologically docked vesicles. Ian Forsythe (Leicester) showed that mitochondria in the terminal play a significant role in determining presynaptic cytoplasmic Ca2+ levels, especially during and following high-frequency trains of impulses. Erwin Neher (Göttingen) presented simultaneous pre- and postsynaptic recordings at the calyx, and proposed that http://tins.trends.com
Heron Island Resort, website http://www.heronisland.com
there are two pools of vesicles, one with high and one with low release probabilities. Two other talks took advantage of large synaptic connections. The intrinsic differences between tonic and phasic synapses were explored by Harold Atwood (Toronto) to refute some common preconceptions of the role of Ca2+-channel density and Ca2+ entry as determinants of release probability. Presynaptic patch-electrode recordings featured again at the small but numerous boutons of cerebellar basket cells, allowing Brian Robertson (London) to directly demonstrate multiple K+-channel types in these basket cell terminals. At the molecular level, Ed Chapman (Madison) presented evidence on the difference between the two Ca2+-binding domains of synaptotagmin, and Sandra Bajjalieh (Seattle) proposed that the synaptic vesicle protein, SV2, might serve to modulate synaptotagmin binding and clustering. One clear take-away message is that vesicles do not have homogeneous properties, and that there is a big gap in reconciling morphology in the terminal with function. Modulation of transmission
Mike Bennett (New York) presented evidence for the rapid insertion of NMDA receptors into membrane, whereas Rosemarie Grantyn (Berlin) showed that
there are complex interactions between GABA receptors, glycine receptors and gephyrin during development. Bob Zucker (Berkeley) and Julie Kauer (Providence) stressed the role of Ca2+ in activating pathways involving second messengers, such as cAMP, in long-term changes of synaptic strength. Guosong Liu (Boston) proposed that differences in the time course of glutamate in the synaptic cleft might modulate synaptic strength and underlie the observation of silent AMPA synapses, and Angus Silver (London) implicated transmitter spillover between synapses in the synaptic cleft at cerebellar mossy fiber terminals. The final session of day two concerned the role of intracellular Ca2+. Tim Bliss (London), Bill Ross (New York), Pankaj Sah (Canberra), Mike Friedlander (Birmingham) and Christian Stricker (Zurich) presented evidence supporting a role for intracellular Ca2+ stores in a range of synaptic processes from LTP to spontaneous transmitter release. Learning about ways in which release can be modulated has the potential to provide more insights into release mechanisms per se, and the more one learns about the modulatory potential in release mechanisms, the more it becomes apparent how much potential plasticity resides in the nerve terminal.
0166-2236/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S0166-2236(00)02066-X
Research Update
Integrative properties of dendrites
Greg Stuart (Canberra), Dan Johnson (Houston), Michael Hausser (London), Mathew Larkum (Heidelberg), Jeff Magee (New Orleans) and Indira Ramon (Chicago) presented data on backpropagation of action potentials, summation of EPSPs and IPSPs, non-linearities involved in detecting coincident inputs at widely separated regions of the dendritic tree, persistent Na+ currents and mechanisms for boosting the strength of distal synaptic inputs. Larry Abbott’s (Brandeis) talk was relevant to this point, as his modeling demonstrated the way that synaptic noise could change the gain of the firing frequency–current relationship in a simple neurone. The transmission of information from synapse to output-spike train also came in for some theoretical attention from Idan Segev (Jerusalem), who introduced the concept of mutual information measures. Inhibitory synapses were also discussed by both Lea Ziskind-Conhaim (Madison) and Albert Berger (Seattle) reporting on spontaneous mIPSCs in spinal and brainstem motoneurones. The mIPSCs could be either glycinergic, GABAergic or a combination of both types. These talks made it clear that the list of computational complexities that a neurone can perform continues to grow, but the discussion often
TRENDS in Neurosciences Vol.25 No.1 January 2002
questioned the physiological relevance of some of these phenomena if they were superimposed upon a membrane potential resulting from a continuous barrage of synaptic inputs rather than at rest. Shaping of network and behavioral responses by synaptic and neuronal properties
One of Don Faber’s (New York) contributions was to show that the goldfish escape response slowed with a drop in temperature and this was paralleled by an increase in the integration time constant of the Mauthner cell. Jeff Smith (Bethesda) described the essential properties of the pre-Botzinger neurones and their connectivity that gives rise to inspiratory rhythm. These neurons must possess a persistent Na+ current and a leak current, and the properties of both currents must be graded throughout the network. Rowland Taylor (Canberra) showed how directional selectivity of retinal ganglion cells was determined by temporal interactions of EPSPs and IPSPs within the ganglion cells. The debate here is whether these mechanisms account for all directional selectivity or whether some presynaptic interactions are also involved. Bill Spain (Seattle) showed how sound localization is signaled by neurones in the nucleus laminaris acting as coincidence detectors for the inputs from both ears to
13
detect inter-aural delays. Yossi Yarom (Jerusalem) discussed synchronized oscillations in membrane potential in neurons in the inferior olive – how their frequency can be altered by synaptic input and how weak electrical coupling preserves synchrony. Cautionary issues of non-uniqueness in ascribing dynamical changes in network behavior to changes in synaptic transmission or to changes in neuronal properties were illustrated by David McCormick (New Haven), using recordings from visual neurons in vivo and in vitro. The meeting ended with Matt Wilson (MIT) relating molecular deletion of NR1 subunit in CA3 hippocampus to spatial-memory performance. NMDA receptors in CA3 are not required for acquisition of spatial reference memory but are required for pattern completion when the number of spatial cues is reduced. The message from this day was that real progress is being made in understanding those networks for which the physiological role is tightly defined. Stephen J. Redman* Bruce Walmsley Division of Neuroscience, John Curtin School of Medical Research, Australian National University, GPO Box 334, Canberra, ACT 2601, Australia. *e-mail: [email protected]
Buenos Aires: Tango makes way for science Branwen Morgan and Marcelo Rubinstein The Joint International and American Neurochemistry Society Meeting was held, in collaboration with SAN (Sociedad Argentina de Neuroquímica), in Buenos Aires, Argentina from 26–31 August 2001.
Stem cells
In August of 2001, 850 neurochemists descended upon Buenos Aires, a city with a passion for Tango. ‘Hot’ science was presented on a wide variety of topics, such as brain gene regulation in cellular life and death processes (including neurodegenerative disease), central nervous system (CNS) regeneration by gene therapy and stem cell transplantation, signal transduction and neuronal plasticity. http://tins.trends.com
Even in the regions of the brain where they reside, neural stem cells are in extremely low abundance, making it difficult to study them. Previously, neural stem cells have been obtained at no more than 5% purity. Now Rod Rietze (Melbourne, Australia) and colleagues have purified a population of brain cells from an adult mouse brain to the point where 80% of the cells have properties of in vitro stem cells [1]. The researchers also studied the differentiation of these neural stem cells, when co-cultured with a muscle cell line, into muscle cells. The signals that allow cell differentiation to take place will obviously feature highly in subsequent investigations. A powerful complementary approach to solving the mystery of the
molecular basis of stem cell plasticity was presented by Annika Dahl (Goteburg, Sweden). Dahl is applying a special type of mass spectrometry (MALDI-TOF MS) to identify peptides and proteins secreted from rat stem cells. In addition to detecting cystatin c, a known protein secreted by stem cells in vitro, she has identified two other proteins with this method that are being investigated for their role in stem cell plasticity. Some valuable clues are also being found from expression profiles of stem cells obtained by microarray analysis. Brain and blood have been turned into each other, like water into wine. Karen Chandross presented elegant work, published last December, demonstrating that bone marrow-derived cells from the
0166-2236/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S0166-2236(00)02039-7