The FGIN period: Electrophysiological studies
Introduction
The electrophysiology laboratory complemented the activity of the various research teams at FGIN and it was the fulfillment of Dr. Costa's dream to be able to study the inhibitory and excitatory synapse in the central nervous system. These studies were facilitated by the development of the patch clamp technique that allows the functional testing of several of the biochemical and pharmacological hypotheses. The studies listed below were the results of the hard work of all the collaborators involved in the projects. I will never forget the passionate and stimulating discussions with Dr. Costa during and after the project development.
Section snippets
Pharmacological modulation of GABAergic transmission in cultured neurons
Inhibitory gamma-aminobutyric acid-mediated synaptic currents were studied in dissociated primary cultures of neonatal rat cortex and postnatal cerebellum with the whole-cell patch-clamp technique [1]. These studies were the results of the graduate work of Dr. Jean Marc Mienville from Montpellier, France. We characterized for the first time the properties of inhibitory synaptic transmission, following the intuition of Dr. Costa that it was central to the action of tranquilizers.
Pharmacological modulation of native and recombinant NMDA channel
In the mid 80s, Costa's laboratory became aware of the crucial role of glutamate receptors, and in particular the NMDA subtype, in brain function and in neurological and psychiatric disorders. Thus together with Dr. Mariella Bertolino (University of Milan) we provided electrophysiological analysis of glutamate receptor channels and the neuropharmacological activity of several important compounds on these channels [5], [6], [7]. We demonstrated that glutamate activates high (40–50 pS) and low
Pharmacological modulation of native and recombinant GABA channel
During the early 1990s, the laboratories of Eric Barnard and Peter Seeburg sequenced and cloned the most important subunits composing the GABA receptor channel. Thus, with the contribution of Giulia Puia, a Postdoctoral fellow from Trieste University, Gianpaolo Mereu, a Visiting Professor from Cagliari University, and Ivica Ducic, a Postdoctoral fellow from Zagreb University, our laboratory characterized the functional and pharmacological heterogeneity of GABA-activated Cl− currents comparing
Properties of GABAA receptors in brain slices studied with visually guided patch-clamp recordings
The development of the patch-clamp technique applied to brain slices in the early 1990s allowed us to characterize the biophysical properties of anatomically defined GABAergic synapses. With Drs. Puia and Mereu, in rat cerebellar slices as well as in dopaminergic neurons of the substantial nigra, we compared whole-cell recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) with Cl− currents resulting from synaptically relevant pulses of GABA (1 mM, <2 ms) to outside-out patches
Properties of glutamate receptors in brain slices studied with visually guided patch-clamp recordings
The patch–clamp technique applied to brain slices allowed us to give three fundamental contributions to the understanding of the heterogeneity of synaptic glutamate receptors.
- 1.
With Dr. Mereu we discovered that both NMDA and AMPA receptors contributes to excitatory synaptic transmission on dopaminergic neurons of the substantia nigra pars compacta, a critical finding in the understanding of roles of these receptors in a variety of conditions, from Parkinson's disease to drug addiction [18].
- 2.
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