UNIVERSITY OF HERTFORDSHIRE
             COMPUTER SCIENCE RESEARCH COLLOQUIUM

                            presents


         "Computational Models of Intracellular Signalling 
           and Synaptic Plasticity Induction in Neurons"

                       Thiago Matos Pinto
                  (School of Computer Science,
                 University of Hertfordshire, UK)

                    17 October 2012  (Wednesday)
                            1 -2  pm


                  Hatfield, College Lane Campus
                      * * Room C152  * *

                  Everyone is Welcome to Attend

                  Refreshments will be available


Abstract:

Mathematical analyses and computer simulations have been established as
valuable approaches to understanding complex systems such as biological
cells. Computational simulation of kinetic models is a powerful tool for
analysing and exploring the behaviour of the complex signal transduction
pathways involved in synaptic plasticity.

I study the intracellular signalling pathways that regulate the induction
of plasticity at synapses in the cerebellum. To investigate and understand
the molecular mechanisms of synaptic plasticity I develop computational
models of signal transduction pathways. These models simulate changes in
the concentration of biochemical compounds in response to extracellular
stimuli and biochemical reactions that occur at synapses.

Calcium/calmodulin (Ca4CaM)-dependent protein kinase II (CaMKII),
which is highly concentrated in the brain, regulates many forms
of synaptic plasticity. Experimental and computational studies have
shown that CaMKII is sensitive to the frequency of oscillatory calcium
signals, and CaMKII has therefore been considered to decode calcium
oscillations. I will demonstrate that the overall activation rate under
sustained application of Ca4CaM pulses ultimately depends on the average
('effective') concentration of (Ca4CaM) in the system, rather than on
the pulse frequency itself, and that the notion of CaMKII as a decoder
of calcium oscillations is misleading.

Moreover, recent experimental observations with Camk2b knockout mice have
revealed that the betaCaMKII isoform mediates the direction of plasticity
at the parallel fibre (PF)- Purkinje cell (PC) synapse. Protocols
that induce long-term depression (LTD) in wild type mice result in
long-term potentiation (LTP) in knockout mice that lack betaCaMKII,
and vice versa. I will present results from computer simulations that
replicate these experimental findings, indicating that the binding of
betaCaMKII to filamentous actin (F-actin) can contribute to the control
of bidirectional plasticity at PF-PC synapses.

---------------------------------------------------
Hertfordshire Computer Science Research Colloquium
http://cs-colloq.stca.herts.ac.uk