In our laboratories, using a combination of experimental and modelling approaches, we study synaptic potentiation and depression
underlying sensitization and habituation of swim induction in the leech Hirudo
medicinalis. In particular, our aim is to assess the roles of the Na+/K+ electrogenic pump, second messenger cascades, control of
the electrotonic activity in the neuritic tree, action potential discharge in these processes.
Behavioural Approaches. In leeches with a microsection below the cephalic ganglion, tactile and/or light electrical stimulation of the
skin, that selectively elicits a burst of action potentials in T neurons, induces swim episodes with a constant latency between the
application of stimuli and the start of swimming. Low rate repetitive stimulation at a constant interstimulus interval (1 min) leads to
an increase of this latency (habituation), whereas nociceptive stimuli bring about a decrease of the latency, in either naive animals
(sensitization) or previously habituated animals (dishabituation). Behavioural investigations showed that 5-HT, via cAMP, and inhibitors
of the Na+/K+ATPase potentiate the swimming induction leading to short term sensitization and dishabituation.
Electrophysiological Approaches. Moreover, 5-HT reduces the amplitude of the after-hyperpolarization (AHP) which follows bursts of
action potentials in mechanosensory T cells of each segmental ganglion. In these neurones the AHP is mainly due to the activation of the
Na+/K+ electrogenic pump and partially to a Ca++-dependent K+ current (gK+/Ca++). The effect of 5-HT is due to the inhibition of the
electrogenic Na+/K+-ATPase and is mediated by cAMP. Moreover, in T neurons, repetitive application of trains of depolarizing impulses at
constant intervals (< 20 sec) elicits a progressive increase in the AHP. Interestingly, agents that block the K+/Ca++ conductance do not
impair the increase of AHP amplitude after repetitive stimulation. We are presently collecting data in order to demonstrate that the
potentiation of the electrogenic pump represents the basic mechanism for habituation. All these results suggest that the modulation
of the Na+/K+ATPase in opposite directions by different inputs might represent a pivotal mechanism for plasticity underlying learning
processes at the cellular level.
Modelling Approaches. Computational studies are developed utilizing the general purpose neural simulator SNNAP. We have developed a
multicompartment model of the T cell, which allowed us to better understand the role played by AHP on the conduction of action potentials
in these cells and more generally in branched neurons. We are currently developing a model of the intracellular biochemical cascade
underlying the above described processes.
- PhD in Neuroscience (dissertation by the end of 2004) Faculty of Science – Department of Physiology and Biochemistry “G. Moruzzi”- University of Pisa - Italy
- Master of Science in Astrophysics Astronomy Unit – School of Mathematical Sciences - QMWC - University of London - U.K. Dissertation Title: “Shear Flow Instability and Accretion Disks”
- Master in Physics Faculty of Science – Department of Physics - University of Pisa – Italy Dissertation Title: “Boundary Conditions in the Coulomb-3-body problem”
|Past & Present Projects:
- In a past project, the role of the AHP amplitude modulation in leech T cells has been analysed. Bursts of spikes in T cells
produce an AHP, which results from activation of a Na+/K+ pump and a Ca2+-dependent K+ current. Activity-dependent increases in the
AHP are believed to induce conduction block of spikes in several regions of the neuron, which in turn, may decrease presynaptic
invasion of spikes and thereby decrease transmitter release. To explore this possibility, we used the neurosimulator SNNAP to
develop a multi-compartmental model of the T cell. The model incorporated empirical data that describe the geometry of the cell and
activity-dependent changes of the AHP. Simulations indicated that at some branching points, activity-dependent increases of the AHP
reduced the number of spikes transmitted from the minor receptive fields to the soma and beyond. More importantly, simulations also
suggest that AHP could modulate, under some circumstances, transmission from the soma to the synaptic terminals, suggesting that the
AHP can regulate spike conduction within the presynaptic arborizations of the cell and could in principle contribute to the synaptic
depression that is correlated with increases in the AHP.
- We are currently modelling the intracellular biochemical cascade underlying the AHP modulation. Data collected in our lab suggest
that, during repetitive electrical stimulation of the T cell, the Ca++ influx through nifedipine-sensitive channels and the Ca++
induced-Ca++ release (CICR) from the intracellular stores play a pivotal role in AHP potentiation. The increase of the intracellular
calcium concentration elicits the 5-lipoxygenase pathway of the arachidonic acid via phospholipaseA2. These metabolites might
up-regulate the Na+/K+ATPase activity. At the same time, the increase of the intracellular calcium concentration could activate the
phospholipaseC, which might down regulate the Na+/K+ATPase activity. In addition the increase cAMP concentration, induced by the
stimulation of serotonergic receptors, down-regulates the Na+/K+ATPase activity. Very recently, experimental studies have shown that
protein kinases A and C are involved in these processes. The model should clarify the role played by the different pathways in the
modulation of the Na+/K+ATPase activity and the several possibilities of cross-talk among these pathways.
- Zaccardi, M.L., Traina, G., Cataldo, E., Brunelli, M. (2001). Nonassociative learning in the leech Hirudo medicinalis. Behavioural Brain Research 126: 81 – 92.
- Cataldo, E., Baxter, D.A., Scuri, R., Byrne, J.H., Brunelli, M. (2002). Computational Model of Leech T Sensory Neuron: Role of Sodium-Potassium Pump in Activity-Dependent Changes of Conduction Failure in Branched Axon. Program Number: 446.9. Abstract viewer/Itinerary Planner. Washington, DC: Society for Neuroscience. 2002 CD-ROM.
- Cataldo, E., Scuri, R., Brunelli, M. (2003). Role of the Na+/K+ Pump in Activity-Dependent Changes of Action Potentials Conduction in Branched Axon of Leech T Sensory Neuron. A Computational Model. Pflügers Arch. ( Eur. J. Physiol.), 445: R, 47, 113.
- Brunelli, M., Scuri, R., Traina, G., Cataldo, E., Lombardo, P., Ristori, C. (2003). Effects of Acetyl-L-Carnitine (ALC) on non Associative Learning Processes in the Leech Hirudo Medicinalis. (2003) Sixth IBRO World Congress of Neuroscience, 3058, CD-ROM.
- Scuri, R., Cataldo, E., Lombardo, P., Brunelli, M. (2003). Molecular mechanism underlying neuronal plasticity in Invertebrate sensory neurons. Congresso Nazionale della Società Italiana di Neuroscienze 26-28 settembre, Pisa
- Brunelli, M., Scuri, R., Traina, G., Zaccardi, M.L., Lombardo, P., Ristori, C., Cataldo, E., Valleggi, S. (2004). Effects of acetyl-l-carnitine (ALC) on invertebrate and vertebrate central nervous system. FENS Forum.
- Zaccardi, M.L., Traina, G., Cataldo, E., Brunelli, M. (in press 2004). Sensitization and Dishabituation of Swim Induction in the Leech Hirudo Medicinalis: Role of Serotonin and Cyclic Amp. Behavioural Brain Research.
- Cataldo, E., Brunelli, M., Byrne, J.H., Av-Ron, E., Cai, Y., Baxter, D.A.(in press 2004). Computational Model of Touch Sensory Cells (T Cells) of the Leech: Role of the Afterhyperpolarization (AHP) in Activity-Dependent Conduction Failure. Journal of Computational Neuroscience.
- Lombardo, P., Scuri, R., Cataldo, E., Calvani, M., Nicolai, R., Mosconi, L., Brunelli, M. (in press 2004) Acetyl-L-carnitine induces a sustained potentiation of the afterhyperpolarization. Neuroscience.