The aim of this thesis is to develop a novel technique for the estimation of firing rate dynamics from single-unit recordings of neural pulse trains. This method applies an offline digital filtering technique to extract information transmitted by a neuron in teens of a rate code. While there is increasing evidence that the traditional rate coding cannot account for all the information transmitted by a cell, and that information may also be contained in the precise timing of spikes, the firing rate signal remains the benchmark by which the vast majority of electrophysiological studies relating neural activity to functional behaviour have been interpreted. Nevertheless, there does not seem to be an agreement on a single definition of a rate code let alone a consensus on an optimal estimation method. This study raises significant concerns about the validity of some of the most common methods in systems neuroscience, and proposes a simple yet more robust alternative. This latter is based on the convolution of the spike train with an optimally designed Kaiser window. Using computer-simulated as well as experimental data obtained from single-unit recordings of vestibular canal afferents, the proposed technique is shown to consistently outperform the current methods and even to permit robust estimations under time-varying conditions. These results suggest that estimates acquired with the conventional methods are biased and hence models of neural dynamics based on these latter may not be reliable.

No description available.

We are interested in understanding the molecular mechanisms that govern synaptic growth and plasticity. Recent evidence from several laboratories suggests that small GTPases play an important role in the promotion of neurite outgrowth; however, their role in the control of synaptic growth and functional plasticity is not well understood. The goal of this thesis is to investigate the role of small GTPases (including Rac, Rho and Cdc42) in the regulation of synaptic growth in vivo, using the Drosophila larval neuromuscular junction (NMJ) synapses as a model system. Our results show that presynaptic overexpression of Rac, but not of Rho or Cdc42, positively regulates both synaptic structure and function. Genetic loss of Rac leads to embryonic lethality, making it impossible to assess the full loss-of-function phenotype using conventional mutants. To circumvent this, we use the MARCM (Mosaic Analysis with a Repressible Cell Marker) technique to generate single motor neuron clones devoid of all genetic copies of Rac. Our data suggest that Rac activity is crucial for normal synaptic development. In support of this conclusion, we demonstrate that genetic removal of trio, a guanine nucleotide exchange factor (GEF) that is known to activate Rac, leads to a drastic reduction in the number of synaptic boutons. In addition, genetic removal of one copy of trio is sufficient to suppress the gain-of-function phenotype of Rac. Moreover, we demonstrate that partial removal of the fragile X mental retardation gene (dfmr1), a known suppressor of Rac, enhances the gain-of-function phenotype of Rac. Taken together, our findings support a model in which Rac signaling positively regulates synaptic growth and function at the Drosophila larval NMJ.

No description available.