Pharmacology of synaptic plasticity

Group Leader

Robert Nisticò

Post Doc
Dalila Mango
Gaia Piccioni Amira Saidi
Pharmacology of synaptic plasticity

Our laboratory aims to understand the molecular basis of synaptic plasticity in both physiological and pathological conditions. In particular, we are focusing on the study of synaptic dysfunctions associated with neurodegenerative and neuroinflammatory diseases, and to identify new therapeutic targets.


We are currently pursuing two projects:


1) Study of the role of ASIC1a channels in Hippocampal Synaptic Plasticity

The acid-sensing ion channel 1 (ASIC1) is widely expressed in the central nervous system. Its role in physiological and pathological synaptic events, however, is still unclear. In recent years, our work has focused on analysing how these channels are implicated in different forms of hippocampal neuronal plasticity with a particular attention to long-term depression (LTD). We are also studying the involvement of these channels in the neuronal dysfunction associated with experimental models of Alzheimer’s disease. Currently, we are also investigating the role of these proteins in the synaptic alterations observed in mouse models of multiple sclerosis.


2) The role of the Complement System in Multiple Sclerosis

The Complement System plays an active role in the onset of multiple sclerosis (MS). Myelin is in fact a primary target of the immune attack in MS. Our previous work has shown that the experimental autoimmune encephalomyelitis (EAE) model presents synaptic dysfunction and loss of synapses due to the production of specific inflammatory cytokines. Several studies have shown that the classic complement pathway plays a central role in the physiological process of pruning, an important step that allows the correct formation of synaptic connections and neuronal circuits. This process is reactivated during aging, neurodegeneration and inflammation, and it is therefore possible to hypothesize that this phenomenon also occurs in Multiple Sclerosis. Indeed, growing evidence has shown that in MS patients, there is an overproduction of complement proteins which tend to accumulate in the synapses of the hippocampus. Our current studies aim to understand the involvement of the complement signal pathway C1q-C3 in the alterations of neurotransmission and synaptic plasticity in the hippocampus of the EAE model. For this research line, our laboratory is in close collaboration with the group directed by Prof Graham Collingridge at the University of Toronto.

Selected Publications


Nisticò R, Salter E, Nicolas C, Feligioni M, Mango D, Bortolotto ZA, Gressens P, Collingridge GL, Peineau S. Synaptoimmunology – roles in health and disease. Mol Brain. 2017 Jun 20;10(1):26. PubMed Full Text

Mango D, Braksator E, Battaglia G, Marcelli S, Mercuri NB, Feligioni M, Nicoletti F, Bashir ZI, Nisticò R. Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus. Pharmacol Res. 2017 May;119:12-19. PubMed

Mango D, Nisticò R. Acid-Sensing Ion Channel 1a Is Involved in N-Methyl D-Aspartate Receptor-Dependent Long-Term Depression in the Hippocampus. Front Pharmacol. 2019 May 21;10:555. PubMed Full Text