Dr Volko Straub
|Tel: 0116 252 3090 Email: email@example.com|
Research Interests and Techniques
I am interested in the study of intrinsic neuronal properties and their short and long-term modulation with a particular emphasis on the neuromodulatory role of nitric oxide and serotonin. Current work in my laboratory concentrates on two major questions:
- The interaction of serotonin and nitric oxide in the modulation of neuronal and synaptic properties
- The role of serotonin and nitric oxide as modulators of neuronal growth and synapse formation in development
My lab studies these questions using two complementary model systems, the pond snail Lymnaea stagnalis as well as acute rat cortical slices and primary cultures of rat cortical neurons. Both model systems have distinct advantages: The relatively simple organisation of the Lymnaea nervous system enables us to directly relate cellular changes to network function and behaviour, while working with rat tissue enables us to transfer ideas developed in the invertebrate model system to a vertebrate system with more direct relevance to human physiology.
To address these questions, my lab uses a combination of approaches including electrophysiological, pharmacological, immunocytochemical, imaging and molecular biology techniques.
Interaction of serotonin and nitric oxide
Plasticity is essential for behavioural adaptations and is achieved by modulation of cellular and synaptic properties. Neuromodulatory systems can themselves be the target for modulation, an effect termed metamodulation. I am particularly interested in the effects of nitric oxide on the modulatory effects of serotonin as there is increasing evidence for a functional overlap between serotonin and nitric oxide. Both modulators affect a wide range of nervous system functions ranging from sensory integration to motor control and learning. Progress in the understanding of the role of nitric oxide and serotonin in these processes depends strongly on a more detailed understanding of the mechanisms of their interactions.
We have previously demonstrated that nitric oxide significantly enhances the effect of serotonin at the cerebral giant cell (CGC) to B4 synapse in Lymnaea1 (see figure below). Current work concentrates on the characterisation of the molecular pathways that mediate the interactions between serotonin and nitric oxide, and the effects of these interactions on cellular properties, synaptic function and behaviour.
In collaboration with Prof Hartell (University of Leicester), we are currently also exploring the effects of interactions between serotonin and nitric oxide on the intrinsic properties and synaptic activity of rat cortical neurons in primary cell cultures and acute brain slice preparations. In the long-term, insights into these interactions could provide the basis for the development of new treatment strategies for psychopathological conditions (e.g. depression, hyper-aggressive behaviour) and other clinical conditions (e.g. migraine, irritable bowel syndrome, erectile dysfunction) that are affected by nitric oxide and serotonin.
Nitric oxide, neuronal growth and memory formation
Long-term memory formation involves the remodeling of existing synapses and the creation of novel synapses. These processes require neurons to undergo morphological changes, i.e. sprouting of new growth cones; extension and/or retraction of spines and processes; formation or removal of synapses. Previous work has demonstrated that nitric oxide plays a significant role in learning and memory formation in Lymnaea1–9, similar to its role in other vertebrate and invertebrate species. In order to study whether endogenous nitric oxide can affect neuronal growth and synapse formation in adult neurons, we studied the effect of nitric oxide signaling on neuronal regeneration and synaptic re-modeling following axonal injury of identified Lymnaea B1 and B2 neurons. This enabled us to demonstrate that nitric oxide significantly modulates both neuronal growth and synaptic re-modelling2.
Based on the observations in Lymnaea we are currently investigating the effects of nitric oxide signaling on neuronal growth and synapse formation in cortical neurons.
Serotonin effects on neuronal development
In addition to acute effects on neuronal and synaptic properties, serotonin has also been shown to affect brain development. For example, alterations in serotonin signaling during early development in humans have been identified as risk factors for the subsequent development of autism, schizophrenia and depression. Animal studies have also shown that experimental manipulation of serotonin signaling during early development leads to changes in brain architecture, in particular in the cerebral cortex. However, it is unclear whether these changes in cerebral cortex architecture are the results of direct actions of serotonin on cortical neurons or whether they are the indirect consequence of serotonin effects on other aspects of brain development. Furthermore, the understanding of the mechanisms by which serotonin signaling affects cortical development is very limited. A new project in my laboratory addresses this issue and studies the effects of serotonergic signaling on growth and synapse formation of cortical neurons, and as a consequence neuronal network function.
Additional Collaborative Projects
- Dr I Tyukin (University of Leicester): Scalable real-time estimation of hidden kinetic parameters in neural cells
- Dr S Ennion (University of Leicester): Cloning and characterisation of a P2X receptor in the pond snail Lymnaea stagnalis
- Dr D Vavoulis & Prof J Feng (University of Warwick): Computational modeling of neuronal properties and network dynamics
Research Group and Funding
Present group members
- Rodrigo Bammann, PhD student
- Yewande Okunoren-Oyekenu, PhD student
- Raghavendra Baliga, MRes student
- PhD studentship, College of Medicine, Biological Sciences and Psychology, University of Leicester: Interaction of serotonin and nitric oxide in the modulation of cortical neuronal properties (2010-2014)
- Wellcome Trust Vacation Scholarship: Mechanism of modulation of serotonergic synapse by nitric oxide (2012)
- BBSRC Project Grant: Nitric Oxide, neuritogenesis and synaptogenesis (2007-2010)
- Wellcome Trust Vacation Scholarship: The effects of axonal lesion on nitric oxide synthase expression and neuronal regeneration (2009)
- Wellcome Trust Vacation Scholarship: Modulation of sensory integration by nitric oxide (2008)
- BBSRC Summer Vacation Bursaries - Yusuf Bhagatte (2007)
Cooke, R. M., Mistry, R., Challiss, R. A. J. & Straub, V. A. Nitric Oxide Synthesis and cGMP Production Is Important for Neurite Growth and Synapse Remodeling after Axotomy. J. Neurosci. 33, 5626–5637 (2013).
Vavoulis, D. V., Straub, V. A., Aston, J. A. D. & Feng, J. A self-organizing state-space-model approach for parameter estimation in hodgkin-huxley-type models of single neurons. PLoS Comput. Biol. 8, e1002401 (2012).
Bavan, S., Straub, V. A., Webb, T. E. & Ennion, S. J. Cloning and characterization of a P2X receptor expressed in the central nervous system of Lymnaea stagnalis. PloS One 7, e50487 (2012).
Bavan, S. et al. The penultimate arginine of the carboxy terminus determines slow desensitization in a P2X receptor from the cattle tick Boophilus microplus. Mol. Pharmacol. (2011). doi:10.1124/mol.110.070037
Straub, V. A. in Encycl. Neurosci. (Binder, M. D., Hirokawa, N. & Windhorst, U.) (Springer, 2009). at <http://dx.doi.org/10.1007/978-3-540-29678-2>
Feng, Z.-P. et al. Transcriptome analysis of the central nervous system of the mollusc Lymnaea stagnalis. BMC Genomics 10, 451 (2009).
Bavan, S., Straub, V. A., Blaxter, M. L. & Ennion, S. J. A P2X receptor from the tardigrade species Hypsibius dujardini with fast kinetics and sensitivity to zinc and copper. BMC Evol. Biol. 9, 17 (2009).
Ribeiro, M. et al. Characterization of NO-sensitive guanylyl cyclase: expression in an identified interneuron involved in NO-cGMP-dependent memory formation. Eur. J. Neurosci. 28, 1157–65 (2008).
Vavoulis, D. V. et al. Dynamic control of a central pattern generator circuit: a computational model of the snail feeding network. Eur. J. Neurosci. 25, 2805–18 (2007).
Straub, V. A., Grant, J., O’Shea, M. & Benjamin, P. R. Modulation of serotonergic neurotransmission by nitric oxide. J. Neurophysiol. 97, 1088–99 (2007).
Kemenes I, Straub VA, Nikitin ES, Staras K, O'Shea M, Kemenes G, Benjamin PR. (2006) Role of delayed nonsynaptic neuronal plasticity in long-term associative memory. Curr Biol. 16: 1269-79.
Straub VA, Kemenes I, O'Shea M, Benjamin PR. (2006) Associative memory stored by functional novel pathway rather than modifications of pre-existing neuronal pathways. J Neurosci. 26: 4139-46.
Arundell M, Patel BA, Straub VA, Allen MC, O Hare D, Parker K, Gard P, Yeoman MS (2006) Deficits in sensory detection contribute to aging in the feeding system of the snail, Lymnaea. Neurobiology of Aging, 27:1880-91.
Korneev S, Straub VA, Kemenes I, Korneeva E, Ott S, Benjamin PR, O’Shea M (2005) Timed and targeted differential regulation of NOS and antiNOS genes by reward conditioning leading to long-term memory formation. J Neurosci 25: 1188-1192.
Straub VA, Styles BJ, Ireland JS, O’Shea M, Benjamin PR (2004) Central localization of plasticity involved in appetitive conditioning in Lymnaea. Learning & Memory 11(6): 787-793.
Straub VA, Staras K, Kemenes G, Benjamin PR (2002) Endogenous and network properties of Lymnaea feeding central pattern generator interneurons. J Neurophysiol 88(4): 1569-83.
Korneev S, Kemenes I, Straub VA, Staras K, Korneeva E, Kemenes G, Benjamin PR, O’Shea M (2002) Suppression of an NO-dependent behavior by dsRNA-mediated silencing of a nNOS gene. J Neurosci 2002 22: RC227.
Perry SJ, Straub VA, Schofield MG, Burke JF, Benjamin PR (2001) Neuronal expression of an FMRFamide-gated Na+ channel and its modulation by acid pH. J Neurosci 21(15): 5559-67.
Straub VA, Benjamin PR (2001) Extrinsic modulation and motor pattern generation in a feeding network: a cellular study. J Neurosci 21(5): 1767-78.
Park JH, Straub VA, O Shea M (1998) Anterograde signalling by nitric oxide: characterization and in vitro reconstitution of an identified nitrergic synapse. J Neurosci 18(14): 5463-76.
Perry SJ, Straub VA, Kemenes G, Santama N, Worster BM, Burke JF, Benjamin PR (1998) Neural modulation of gut motility by myomodulin peptides and acetylcholine in the snail Lymnaea. J Neurophysiol 79(5): 2460-74.
Peschel M, Straub V, Teyke T (1996) Consequences of food-attraction conditioning in Helix: A behavioral and electrophysiological study. J Comp Physiol A 178 (3): 317-327.