What We Study

Our research aims at understanding pathophysiological mechanisms and developing new treatments for disorders affecting the basal ganglia, particularly Parkinson´s Disease (PD). To facilitate this research, we have pioneered the development of rodent models having both face and construct validity relative to hypokinetic and dyskinetic disorders in humans. These models are now broadly used for basic and translational research worldwide. In addition, we are now developing new models exhibiting cognitive and neuropsychiatric features relevant to PD. In several ongoing projects, we are comparing the effects of both existing and emerging PD therapies on multiple functional domains, and investigating the associated neuroplastic changes at multiple levels (signaling pathway activation, gene expression, synaptic plasticity, gliovascular reactivity, neurovascular coupling).

Methods We Use

Ex-vivo electrophysiology and two-photon imaging

We use a dual patch-clamp recording & stimulation setup integrated within a two-photon laser microscope in order to investigate the relationship between structure and function in neurons and microcircuits. For example, with this system we are studying changes in dendritic morphology, intrinsic excitability, and synaptic plasticity that affect specific types of basal ganglia neurons in rodent models of PD and L-DOPA-induced dyskinesia.

Advanced behavioral analyses

Basal ganglia disorders are associated with different types of motor dysfunction, ranging from abnormally slow movements to excessive uncontrollable movements. They also cause a range of cognitive and neuropsychiatric deficits, such as reduced attentional and executive capacity, and apathy or impulsivity. To capture and categorize these composite phenotypes, we use several behavioural test setups that allow us to evaluate both motor and non-motor features in mice and rats. Moreover, we have recently built an advanced set-up for high-speed videography including high performance GPU-enabled computational platforms and machine learning algorithms.

In-Vivo Photometry

We use fiber photometry with genetically encoded calcium indicators (GECI) to record the activity of specific populations of neurons in freely behaving animals. We are also able to record from two different cell types simultaneously using a dual-fluorescence recording system. Fiber photometry can also be used to study neurotransmitter release, or the activation of specific intracellular signalling pathways, using specifically designed genetically encoded sensors. Our photometry system is part of an advanced recording setup including high-speed videography of animal motions.

Histomolecular and biochemical assays

We have large laboratory space hosting equipment for molecular biology, biochemistry, histology, bright-field and fluorescence microscopy. We use these multiple approaches when we characterise new animal models of neurodegenerative disorders (for example, rodent models of PD based on genetic technologies or targeted inoculations of misfolded proteins), and also when we evaluate the effects of different treatments.

Representative Publications

2021

Distinct patterns of dyskinetic and dystonic features following D1 or D2 receptor stimulation in a mouse model of parkinsonism,

Laura Andreoli, Morteza Abbaszadeh*, Xiao Cao* & Maria Angela Cenci,

In: Neurobiology of Disease 2021. PMID 34153463

2020

D1-mGlu5 heteromers mediate noncanonical dopamine signaling in Parkinson’s disease

Sebastianutto I*, Goyet, E*, Andreoli L., Font-Ingles J., Moreno-Delgado, D., Bouquier, N., Jahannault-Talignani, C., Moutin, E., Di Menna, L., Maslava, N., Pin, J. P., Fagni, L., Nicoletti, F., Ango, F., M. Angela Cenci *& Perroy, J.*,

In: Journal of Clinical Investigation 2020, PMID 32039920

Current projects

2021- 2026

Lundbeck Foundation, grant no. R336-2020-1035, PI: H. Siebner, 2021-2026

ADAPT-PD (ADAptive and Precise Targeting of cortex-basal ganglia circuits in Parkinson´'s Disease)

The goal of this project is to identify alterations in network dynamics causing motor and non-motor impairments in PD, and to develop new precise therapeutic approaches based on non-invasive neuromodulation.

Cenci Nilsson's role: Coinvestigator, responsible for the rodent studies

2020-2024

Swedish Research Council (SRC), grant 2020-02696, PI: Cenci Nilsson, 2021-2024

Parkinson’s disease: interplay of cells and circuits in the genesis of movement disorders

The goal of this project is to elucidate circuit dysfunctions underlying hypokinetic, hyperkinetic, and dystonic movement disorders in PD.

Cenci Nilsson' s role: PI

2019-2024

NIH/NINDS, grant no. 1R01NS105979-01A1, PI: David Eidelberg), 2019-2024

Neurovascular effects of dopamine replacement therapy in Parkinson’s disease

The goal of this project is to determine the time course and functional significance of neurovascular changes induced by dopamine replacement in PD. Cenci Nilsson's role: Coinvestigator, responsible for the rodent studies.

2019-2022

Swedish Government Funds for Clinical Research, ALF project-43301, PI: Cenci Nilsson, 2019-2022

Pathophysiology-guided drug treatments for Parkinson’s disease

The goal of this project is to translate results from multiple lines of preclinical investigations into new potential disease-modifying and symptomatic treatments for PD. Cenci Nilsson's role: PI

2019-2021

Swedish Brain Foundation, FO2019-0156, PI: Cenci Nilsson, 2019-2021

New models of pathology propagation and symptom development in Parkinson’s Disease.

The goal of this project is to create new rat models of synucleinopathy based on long-range transmission of pathogenic proteins in specific brain circuits.

Cenci Nilsson's role: PI