Cortical microcircuits and neurodevelopmental disorders

Group Leader

Marilena Griguoli

Associated scientist
Enrico Cherubini
Post Doc
Domenico Pimpinella
PH. D. Student
Brijesh Modi
Master student
Alice Tartacca Christian Jacobs
Cortical microcircuits and neurodevelopmental disorders

Aim of our laboratory is to study the molecular and cellular mechanisms involved in social memory both in physiological and pathological conditions, particularly in Neurodevelopmental Disorders such as Autism Spectrum Disorders. Our team is involved in two research lines:​

  1.  ​From microcircuits to behavior​

The hippocampus is critically involved in spatial memory. Recently, the relevance of the CA2 hippocampal area for social memory encoding, namely the capacity to remember a conspecific, has been highlighted. The aim of our research is to understand the mechanisms by which, within the CA2 circuit, local GABAergic interneurons and cholinergic inputs originating in the medial septum contribute to this form of memory. This is achieved via electrophysiological (both in vivo and ex vivo) and behavioral approaches combined with opto/chemogenetic tools. Opto/chemogenetics will allow to selectively activate/silence inhibitory or cholinergic pathways. Our final goal is to dissect the contribution of different components of the CA2 neuronal circuit involved in social memory formation.

  1.  Changes in microcircuit dynamics in Autism Spectrum Disorders

We aim at exploring the impact of trans-synaptic signaling underlying the formation of neuronal circuits in health and disease, particularly in Neurodevelopmental Disorders such as Autism Spectrum Disorders (ASDs).

ASDs comprise a wide range of neuro-developmental disorders characterized by deficits in verbal and non-verbal communication, impaired social interactions, restricted interest, and stereotyped behavior. Among monogenetic forms of ASDs, of particular interest are those related to single mutations of genes encoding for adhesion molecules of the neuroligin (NLG)/neurexin (NRX) families. NLGs are postsynaptic proteins that by interacting with their presynaptic partners, NRXs, functionally couple the postsynaptic densities with the transmitter release machinery, thus contributing to synapses stabilization. Our goal is to study the molecular and cellular mechanisms underlying alterations of the excitatory (E)/inhibitory (I) balance in the hippocampus of transgenic mice carrying the human R451C mutation of the Nlgn 3 gene (NLG3R451C knock-in) or in mice lacking NLG3 (NLG3  knock-out), both animal models of ASDs.

Using a variety of different approaches (molecular biology, in vivo and ex vivo electrophysiology, opto-chemogenetics, imaging and behavior) we aim at elucidating how an altered E/I balance in selective neuronal circuits affects theta and gamma rhythm generation, thought to be  involved in high cognitive functions. The final objective is to identify new targets for therapeutic intervention.



Selected publications

Pimpinella D, Mastrorilli V, Giorgi C, Coemans S, Lecca S, Lalive AL, Ostermann H, Fuchs EC, Monyer H, Mele A, Cherubini E, Griguoli M. Septal cholinergic input to CA2 hippocampal region controls social novelty discrimination via nicotinic receptor-mediated disinhibition. eLife 2021;10:e65580, 2021

Modi B, Pimpinella D, Pazienti A, Zacchi P, Cherubini E, Griguoli M. Possible implication of the CA2 hippocampal circuit in social cognition deficits observed in the neuroligin 3 knock-out mouse, a non-syndromic animal model of Autism. Front Psychiatry 10: 513, 2019

Griguoli M, Cellot G, Cherubini E. In hippocampal oriens interneurons anti-Hebbian Long-Term Potentiation requires cholinergic signalling via ɑ7 nicotinic acetylcholine receptors. Journal of Neuroscience, 33(3):1044-1049, 2013