- Neuroscience and Neuropharmacology Research
- Neurological disorders and treatments
- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- Neural dynamics and brain function
- Autism Spectrum Disorder Research
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Nicotinic Acetylcholine Receptors Study
- Neurotransmitter Receptor Influence on Behavior
- Botulinum Toxin and Related Neurological Disorders
- Memory and Neural Mechanisms
- Photoreceptor and optogenetics research
- RNA regulation and disease
- Phosphodiesterase function and regulation
- Nuclear Receptors and Signaling
- Transcranial Magnetic Stimulation Studies
- Cell death mechanisms and regulation
- Nitric Oxide and Endothelin Effects
- Epilepsy research and treatment
- Metabolism and Genetic Disorders
- Pain Mechanisms and Treatments
Fondazione Santa Lucia
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2014-2024
University of Pavia
2021
University of Rome Tor Vergata
2000-2013
European Brain Research Institute
2006-2007
Istituto Superiore di Sanità
1999-2002
Novem (Netherlands)
2002
Sapienza University of Rome
1994-1999
Parkinson's disease (PD) is characterized by the selective vulnerability of nigrostriatal dopaminergic circuit. Recently, loss-of-function mutations in PTEN-induced kinase 1 (PINK1) gene have been linked to early-onset PD. How PINK1 deficiency causes dysfunction and degeneration PD patients unknown. Here, we investigate physiological role circuit through generation multidisciplinary analysis PINK1(-/-) mutant mice. We found that numbers neurons levels striatal dopamine (DA) DA receptors are...
DYT1 dystonia is a severe form of inherited dystonia, characterized by involuntary twisting movements and abnormal postures. It linked to deletion in the dyt1 gene, resulting mutated protein torsinA. The penetrance for incomplete, but both clinically affected non-manifesting carriers mutation exhibit impaired motor learning evidence altered plasticity. Here, we striatal glutamatergic synaptic plasticity transgenic mice expressing either normal human torsinA or its mutant form, comparison...
Work over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in context of basal ganglia function. The recognition that these are essential synaptic plasticity and motor learning represents significant step ahead deciphering how striatum processes cortical inputs, why pathological circumstances cause dysfunction. Loss reciprocal modulation between dopaminergic inputs intrinsic innervation within appears to be trigger pathophysiological changes...
Cortical spreading depression (CSD) is a key pathogenetic step in migraine with aura. Dysfunctions of voltage-dependent and receptor-operated channels have been implicated the generation CSD pathophysiology migraine. Although known correlation exists between release calcitonin gene-related peptide (CGRP), possibility that CGRP involved has not examined detail. We analyzed pharmacological mechanisms underlying investigated endogenous contributes to this phenomenon. was rat neocortical slices...
The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses critically involved motor memory. In the Tor1a+/Δgag mouse model, long-term potentiation (LTP) appeared prematurely a critical window striatal spiny neurons (SPNs), while depression (LTD) was never recorded. Analysis dendritic spines showed an increase both spine width mature...
Dopamine (DA) plays a crucial role in the modulation of striatal function. Striatal cholinergic interneurons represent an important synaptic target dopaminergic fibers arising from substantia nigra and cortical glutamatergic inputs. By means electrophysiological approach corticostriatal slices, we isolated three distinct inputs to interneurons: glutamate-mediated EPSPs, GABAA-mediated potentials, Acetylcholine (ACh)-mediated IPSPs. We therefore explored whether DA controls activity through...
Abnormal involuntary movements and cognitive impairment represent the classical clinical symptoms of Huntington's disease (HD). This genetic disorder involves degeneration striatal spiny neurons, but not large cholinergic interneurons, corresponds to a marked decrease in activity mitochondrial complex II [succinate dehydrogenase (SD)] brains HD patients. Here we have examined possibility that SD inhibitors exert their toxic action by increasing glutamatergic transmission. We report such as...
Summary: Purpose: Alterations in neuronal calcium (Ca 2+ ) homeostasis are believed to play an essential role the generation and propagation of epileptiform events. Levetiracetam (LEV) lamotrigine (LTG), novel antiepileptic drugs (AEDs), were tested on events corresponding elevations intracellular Ca concentration ([Ca ] i recorded from rat neocortical slices. Methods: Electrophysiological recordings performed single pyramidal neurons a slice preparation. Spontaneous consisting long‐lasting,...
Projections from thalamic intralaminar nuclei convey sensory signals to striatal cholinergic interneurons. These neurons respond with a pause in their pacemaking activity, enabling synaptic integration cortical inputs medium spiny (MSNs), thus playing crucial role motor function. In mice the DYT1 dystonia mutation, stimulation of thalamostriatal axons, mimicking response salient events, evoked shortened and triggered an abnormal spiking activity This altered pattern caused significant...
Broad-spectrum muscarinic receptor antagonists have represented the first available treatment for different movement disorders such as dystonia. However, specificity of these drugs and their mechanism action is not entirely clear. We performed a systematic analysis effects anticholinergic on short- long-term plasticity recorded from striatal medium spiny neurons DYT1 dystonia knock-in (Tor1a(+/Δgag) ) mice heterozygous ΔE-torsinA controls (Tor1a(+/+) mice). Antagonists were chosen that had...
Muscarinic autoreceptors regulate cholinergic tone in the striatum. We investigated functional consequences of genetic deletion striatal muscarinic by means electrophysiological recordings from either medium spiny neurons (MSNs) or interneurons (ChIs) slices single M<sub>4</sub> double M<sub>2</sub>/M<sub>4</sub> acetylcholine receptor (mAChR) knock-out (−/−) mice. In control ChIs, agonist oxotremorine (300 nm) produced a self-inhibitory outward current that was mostly reduced...