Giorgio Grasselli

Università degli Studi di Genova | UNIGE · Department of Pharmacy (DIFAR)

Neurons store information by changing synaptic input weights. In addition, they can adjust their membrane excitability to alter spike output. Here, we demonstrate a role of such “intrinsic plasticity” in behavioral learning in a mouse model that allows us to detect specific consequences of absent excitability modulation. Mice with a Purkinje-cell–s...

Postnatal cerebellar development is a precisely regulated process involving well-orchestrated expression of neural genes. Neurological phenotypes associated with CACNA1A gene defects have been increasingly recognized, yet the molecular principles underlying this association remain elusive. By characterizing a dose-dependent CACNA1A gene deficiency...

The plasticity of intrinsic excitability has been described in several types of neurons, but the significance of non-synaptic mechanisms in brain plasticity and learning remains elusive. Cerebellar Purkinje cells are inhibitory neurons that spontaneously fire action potentials at high frequencies and regulate activity in their target cells in the c...

Plasticity in the central nervous system in response to injury is a complex process involving axonal remodeling regulated by specific molecular pathways. Here, we dissected the role of growth-associated protein 43 (GAP-43; also known as neuromodulin and B-50) in axonal structural plasticity by using, as a model, climbing fibers. Single axonal branc...

Background Autism spectrum disorder (ASD) patients often show altered responses to sensory stimuli as well as motor deficits, including an impairment of delay eyeblink conditioning (EBC), which involves integration of sensory signals in the cerebellum. Here, we identify abnormalities in parallel fiber (PF) and climbing fiber (CF) signaling in mouse...

Objective Transcranial magnetic stimulation (TMS) delivered over the cerebellum 5–7 ms prior to a stimulus over the contralateral primary motor cortex (M1) reduces the excitability of M1 output, a phenomenon termed cerebellar brain inhibition (CBI). The cerebellum receives sensory information for adaptive motor coordination and motor planning. Here...

Optical technologies allowing modulation of neuronal activity at high spatio-temporal resolution are becoming paramount in neuroscience. In this respect, azobenzene-based photoswitches are promising nanoscale tools for neuronal photostimulation. Here we engineered a light-sensitive azobenzene compound (Ziapin2) that stably partitions into the plasm...

Significance Instructive signals play an important role in synaptic plasticity and learning. For example, at cerebellar parallel fiber (PF)-Purkinje cell synapses, climbing fiber (CF) coactivation provides an instructive signal that promotes long-term depression (LTD) by amplifying spine calcium transients above a threshold level that, at these syn...

The development of multiple sclerosis, a major neurodegenerative disease, is due to both genetic and environmental factors that might trigger aberrant epigenetic changes of the genome. In this study, we analysed global DNA methylation in the brain of mice upon induction of experimental autoimmune encephalomyelitis (EAE), and the effect of environme...

Public dissemination of science is often negatively affected by biased, incorrect information distributed over the internet through social networks and blogs. In Italy, the lack of correct scientific information has generated several important issues, raising concerns by the international scientific community in several occasions over the past five...

Wild-type values for eyeblink conditioning parameters.Last column, results of comparison across all wild-type cohorts. Statistical test indicated.DOI: http://dx.doi.org/10.7554/eLife.06085.004

Activity-dependent long-term plasticity of synaptic transmission, such as in long-term potentiation (LTP) and long-term depression (LTD), provides a cellular correlate of experience-driven learning. While at excitatory synapses in the hippocampus and neocortex LTP is seen as the primary learning mechanism, it has been widely assumed that cerebellar...

A common feature of autism spectrum disorder (ASD) is the impairment of motor control and learning, occurring in a majority of children with autism, consistent with perturbation in cerebellar function. Here we report alterations in motor behaviour and cerebellar synaptic plasticity in a mouse model (patDp/+) for the human 15q11-13 duplication, one...

Cerebellar deficit contributes significantly to disability in multiple sclerosis (MS). Several clinical and experimental studies have investigated the pathophysiology of cerebellar dysfunction in this neuroinflammatory disorder, but the cellular and molecular mechanisms are still unclear. In experimental autoimmune encephalomyelitis (EAE), a mouse...

In the adult nervous system, different neuronal classes show different regenerative behavior. Although previous studies demonstrated that olivocerebellar fibers are capable of axonal regeneration in a suitable environment as a response to injury, we have hitherto no details about the real dynamics of fiber regeneration. We set up a model of singula...

Structural plasticity occurs physiologically or after brain damage to adapt or re-establish proper synaptic connections. This capacity depends on several intrinsic and extrinsic determinants that differ between neuron types. We reviewed the significant endogenous regenerative potential of the neurons of the inferior olive (IO) in the adult rodent b...

In the adult nervous system, different populations of neurons correspond to different regenerative behavior. Although previous works showed that olivocerebellar fibers are capable of axonal regeneration in a suitable environment as a response to injury1, we have hitherto no details about the real dynamics of fiber regeneration. We set up a model of...

Glutamate-mediated excitotoxicity is supposed to induce neurodegeneration in multiple sclerosis (MS). Glatiramer acetate (GA) is an immunomodulatory agent used in MS treatment with potential neuroprotective action. Aim of the present study was to investigate whether GA has effects on glutamate transmission alterations occurring in experimental auto...

Ethanol profoundly influences cerebellar circuit function and motor control. It has recently been demonstrated that functional NMDA receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in the adult cerebellum. Using whole-cell patch-clamp recordings from mouse cerebellar slices, we examined whether ethanol can a...

Glutamate transmission is dysregulated in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the animal model of MS. A characteristic of EAE is increased glutamate transmission associated with up-regulation of AMPA receptors. However, little is known about the role of NMDA receptors in the synaptic modifications induc...

In the adult nervous system, different population of neurons corresponds to different regenerative behavior. Although previous works show that olivocerebellar fibers are capable of axonal regeneration in a suitable environment as a response to injury [1], we have hitherto no details about the real dynamics of fiber regeneration. We coupled two phot...

Injection of viral particles, transduction and CF labelling. (A) An example of brainstem of a rat injected with control (GFP-only) viral suspension, as observed by combined DIC and fluorescent microscopy for GFP signal (coronal section). The injection successfully reached the IO in the brain stem and induced the expression of GFP in part of the IO...

Sprouting of CFs transduced with lentiviral vectors following subtotal lesion of the IO. Projections of series of optical sections obtained by confocal microscopy from sagittal (A–B) and coronal sections (C–E) of animals injected with control viral particles (expressing only GFP) and treated with 3-AP to induce the death of most neurons in the IO (...

The adult mammalian central nervous system has a limited ability to establish new connections and to recover from traumatic or degenerative events. The olivo-cerebellar network represents an excellent model to investigate neuroprotection and repair in the brain during adulthood, due to its high plasticity and ordered synaptic organization. To shed...

Transient receptor potential vanilloid 1 (TRPV1) channels are involved in several inflammatory diseases. However, their action is still controversial, and both pro-inflammatory and anti-inflammatory roles have been described. We used a strain of TRPV1-KO mice to characterize the role of these channels in experimental autoimmune encephalomyelitis (E...

Multiple sclerosis (MS) is characterized by auto-reactive T cells that respond to central nervous system (CNS)-based antigens and affect motor, sensory as well as behavioral and cognitive functions. Cognitive deficits are now considered an early manifestation of the disease in MS patients. However, the pathophysiology responsible for the cognitive...

Synaptic dysfunction triggers neuronal damage in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). While excessive glutamate signaling has been reported in the striatum of EAE, it is still uncertain whether GABA synapses are altered. Electrophysiological recordings showed a reduction of spontaneous GABAergic synap...

In combination with fluorescent protein (XFP) expression techniques, two-photon microscopy has become an indispensable tool to image cortical plasticity in living mice. In parallel to its application in imaging, multi-photon absorption has also been used as a tool for the dissection of single neurites with submicrometric precision without causing a...

In the adult nervous system, different population of neurons corresponds to different regenerative behavior. Although previous works show that olivocerebellar fibers are capable of axonal regeneration in a suitable environment as a response to injury1, we have hitherto no details about the real dynamics of fiber regeneration. We coupled two photon...

Synaptosome-associated protein of 25 kDa (SNAP25) is a component of the fusion complex that mediates synaptic vesicle exocytosis, regulates calcium dynamics and neuronal plasticity. Despite its crucial role in vesicle release, SNAP25 is not distributed homogenously within the brain. It seems to be virtually absent in mature inhibitory terminals and...