Neurons and microglia in the physiopathology of cortical microcircuits and retina

Group Leader

Silvia Marinelli

PhD
Lucia Buccarello Marina Di Domenico Domenico Guarascio Pietro Renna
Laboratory
Neurons and microglia in the physiopathology of cortical microcircuits and retina

The main interests of my laboratory are understanding i) the role of the inhibitory synaptic plasticity and ii) the specific molecular signals underlying the bidirectional interaction between neurons and microglia, in physio-pathological conditions. To reach these aims we use both in vivo and ex vivo approaches: behavioural tasks, electrophysiology and SCSR-confocal microscopy.

 

  1. Microglia-neuron communication in pathophysiological conditions

 

The resident immune cells of the brain are engaged in sculpting neuronal circuits and in the preservation of neuronal homeostasis. To execute their functions, microglial cells must sense neuronal activity. Viceversa, neurons must detect microglia signals to correctly and accurately operate and communicate with each-other. These interactions are ensured by the reciprocal expression of a variety of different neurotransmitter and neuromodulator receptors that are activated by microglia and by neuron-released molecules. In neurological diseases in which neuroinflammation is prevalent, such as Alzheimer, multiple sclerosis, epilepsy and chronic pain, the bidirectional neuronal-microglial communication is altered, affecting both synaptic activity and plasticity, and potentially causing profound changes in nervous circuits and associated functions.

Based on this evidence, we are investigating the molecular mechanisms and the site of action by which microglia control neuronal activity/function, with a particular focus on endocannabinoids and neurotrophins. At present, we are inquiring about microglia contribution to the induction/formation and consolidation of the traces of memory, at the synaptic scale (synaptic memory engrams) and microglia role in the neurodegeneration/neuroprotection of retinal ganglion cells.

Finally, our research aims at finding key proteins as strategic targets to control neurodegeneration.

 

  1. Inhibitory synaptic plasticity in cortical microcircuits

 

 

Objective of this research line concerns the characterization of synaptic and plasticity properties of GABAergic synapses in both physiological and disease contexts. So far, we have been studying mechanisms of homeostatic non Hebbian plasticity in cortical microcircuits and identified specific interneuron subtypes and retrograde messengers (i.e. endocannabinoids and NO) involved in this form of synaptic plasticity.  Our current interests are to explore changes in long-term synaptic inhibitory properties following specific neuronal stimulation patterns and behavioural tasks, in order to understand the role of inhibitory synapses in certain cognitive functions, such as memory and learning, and sensory processing.

 

In collaboration with the research group of Professor Cattaneo, we are studying the physiology and anatomy of memory engrams at the synaptic level, by exploiting Synactive, a genetically encoded tool developed by his lab, allowing the selective identification and analysis of potentiated synapses.

 

Selected Publications

 

Marinelli S, Basilico B, Marrone MC, Ragozzino D. Microglia-neuron crosstalk: Signaling mechanism and control of synaptic transmission. Semin Cell Dev Biol. 2019 Oct;94:138-151. doi: 10.1016/j.semcdb.2019.05.017. Epub 2019 May 30. Review. PubMed PMID: 31112798.

Marrone MC, Morabito A, Giustizieri M, Chiurchiù V, Leuti A, Mattioli M, Marinelli S, Riganti L, Lombardi M, Murana E, Totaro A, Piomelli D, Ragozzino D, Oddi S, Maccarrone M, Verderio C, Marinelli S. TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice. Nat Commun. 2017 May 10;8:15292. doi: 10.1038/ncomms15292. PubMed PMID: 28489079; PubMed Central PMCID: PMC5436240.

Marinelli S, Pacioni S, Cannich A, Marsicano G, Bacci A. Self-modulation of neocortical pyramidal neurons by endocannabinoids. Nat Neurosci. 2009 Dec;12(12):1488-90. doi: 10.1038/nn.2430. Epub 2009 Nov 15. PubMed PMID: 19915567.