Neurobiology of learning
How is our brain modified by experience, sensory deprivation, drugs and disease? It is unquestionable that behind any behavior there are molecular and functional changes in synapses and synaptic circuits. Antonio Malgaroli was the first scientist to demonstrate satisfactorily that the maintenance of the synaptic learning process known as Long-term Potentiation or LTP, discovered by Tim Bliss and Thierry Lomo in 1973, has a presynaptic component. Despite in the last 20 years we have been spectators of an incredible advancement in the elucidation of molecular machinery of synapses, the exact functional mechanisms behind synaptic communication and LTP are still largely unknown. This partial failure has indeed some solid grounds. Today brain synapses are still pproached very indirectly because they are very small (less than 1 micron), they produce small signals (a few picoamperes), they are difficult to access being located on thin and complex dendritic cables, they are heterogeneous in structure and in biochemical composition, undergoing continuous and fast complex biochemical-morphological rearrangements.
To overcome some of these limitations, Antonio Malgaroli and his lab have dedicated a lot of efforts to develop novel tools for the investigation of synapses. His current research aims at:
- Defining the nature of the basic parameters of quantal transmission and how these are changed by the learning process;
- Enhancing and testing SynaptoZip, a novel genetically-encoded synaptic activity sensor recently developed in his lab, which is able to report the activity of individual synaptic boutons in the in vivo brain;
- Obtaining new in vitro models of brain circuits based on nanostructured substrates;
- Studying the role of dopamine in modulating synaptic plasticity in the prefrontal cortex in relation to animal behavior and mental disorders;
- Clinical and basic investigation of the Tourette syndrome.
M. Ferro*, J. Lamanna*, M. Ripamonti*, G. Racchetti, A. Arena, S. Spadini, G. Montesano, R. Cortese, V. Zimarino & A. Malgaroli. Functional mapping of brain synapses by an enriching activity-marker. Nature Communications, Oct 31;8(1):1229, 2017. (*equal contribution)
C. Schulte, M. Ripamonti, E. Maffioli, M.A. Cappelluti, S. Nonnis, L. Puricelli, J. Lamanna, C. Piazzoni, A. Podestà, C. Lenardi, G. Tedeschi* , A. Malgaroli* & P. Milani* Scale invariant disordered nanotopography promotes hippocampal neuron development and maturation with involvement of
mechanotransductive pathway. Frontiers Cell Neuroscience. 10:267, 2016.
Arena A, Lamanna J, Gemma M, Ripamonit M, Ravasio G, Zimarino V, De Vitis A, Beretta L, & Malgaroli A. A linear transformation of the encoding mechanism for light-intensity underlies paradoxical enhancement of cortical visual responses by sevoflurane. J. Physiology Jan 1;595(1):321-339, 2017.
Lamanna, J., Signorini, M. G., Cerutti, S., and Malgaroli, A. A pre-docking source for the power-law behavior of spontaneous quantal release: application to the analysis of LTP. Frontiers in Cellular Neuroscience 9(44), 2015.
Treccani G, Musazzi L, Perego C, Milanese M, Nava N, Bonifacino T, Lamanna J, Malgaroli A, Drago F, Racagni G, Nyengaard JR, Wegener G, Bonanno G, Popoli M. Acute stress rapidly increases the readily releasable pool of glutamate vesicles in prefrontal and frontal cortex through non-genomic action of corticosterone. Mol Psychiatry. 19:433-43, 2014.
Abenavoli, A., L. Forti, Bossi M., Bergamaschi A., Villa A. & Malgaroli A. Multimodal quantal release at hippocampal synapses: evidence for lack of lateral inhibition. J. Neuroscience 22: 6336-6346, 2002.
Malgaroli, A. Silent synapses: I can’t hear you! Could you please speak aloud. Nature Neuroscience, 2 : 3-5, 1999.
Forti, L., Bossi, M., Bergamaschi, A., Villa, A. & Malgaroli, A. (1997) Loose-patch recordings of single quanta at individual hippocampal synapses, Nature 338: 874-878.
Malgaroli, A., Ting, A.E., Wendland, B., Bergamaschi, A., Villa, A., Tsien, R.W., & Scheller, R.H. (1995) Presynaptic Component of Long-term Potentiation Visualized at Individual Hippocampal Synapses. Science 268: 1624-1628.
Malgaroli, A. & Tsien, R.W. (1992) Glutamate-induced long-term potentiation of the frequency of miniature synaptic currents in cultured hippocampal neurons. Nature, 357: 134-139.