Time filter

Source Type

Sciamanna G.,Laboratory of Neurophysiology and Plasticity | Wilson C.J.,University of Texas at San Antonio
Journal of Neurophysiology | Year: 2011

Striatal fast-spiking (FS) cells in slices fire in the gamma frequency range and in vivo are often phase-locked to gamma oscillations in the field potential. We studied the firing patterns of these cells in slices from rats ages 16-23 days to determine the mechanism of their gamma resonance. The resonance of striatal FS cells was manifested as a minimum frequency for repetitive firing. At rheobase, cells fired a doublet of action potentials or doublets separated by pauses, with an instantaneous firing rate averaging 44 spikes/s. The minimum rate for sustained firing was also responsible for the stuttering firing pattern. Firing rate adapted during each episode of firing, and bursts were terminated when firing was reduced to the minimum sustainable rate. Resonance and stuttering continued after blockade of Kv3 current using tetraethylammonium (0.1-1 mM). Both gamma resonance and stuttering were strongly dependent on Kv1 current. Blockade of Kv1 channels with dendrotoxin-I (100 nM) completely abolished the stuttering firing pattern, greatly lowered the minimum firing rate, abolished gamma-band subthreshold oscillations, and slowed spike frequency adaptation. The loss of resonance could be accounted for by a reduction in potassium current near spike threshold and the emergence of a fixed spike threshold. Inactivation of the Kv1 channel combined with the minimum firing rate could account for the stuttering firing pattern. The resonant properties conferred by this channel were shown to be adequate to account for their phase-locking to gamma-frequency inputs as seen in vivo. © 2011 the American Physiological Society.

Sciamanna G.,University of Rome Tor Vergata | Sciamanna G.,Laboratory of Neurophysiology and Plasticity | Tassone A.,University of Rome Tor Vergata | Tassone A.,Laboratory of Neurophysiology and Plasticity | And 11 more authors.
PLoS ONE | Year: 2011

Background: DYT1 dystonia, a severe form of genetically determined human dystonia, exhibits reduced penetrance among carriers and begins usually during adolescence. The reasons for such age dependence and variability remain unclear. Methods and Results: We characterized the alterations in D2 dopamine receptor (D2R) signalling in striatal cholinergic interneurons at different ages in mice overexpressing human mutant torsinA (hMT). An abnormal excitatory response to the D2R agonist quinpirole was recorded at postnatal day 14, consisting of a membrane depolarization coupled to an increase in spiking frequency, and persisted unchanged at 3 and 9 months in hMT mice, compared to mice expressing wild-type human torsinA and non-transgenic mice. This response was blocked by the D2R antagonist sulpiride and depended upon G-proteins, as it was prevented by intrapipette GDP-β-S. Patch-clamp recordings from dissociated interneurons revealed a significant increase in the Cav2.2-mediated current fraction at all ages examined. Consistently, chelation of intracellular calcium abolished the paradoxical response to quinpirole. Finally, no gross morphological changes were observed during development. Conclusions: These results suggest that an imbalanced striatal dopaminergic/cholinergic signaling occurs early in DYT1 dystonia and persists along development, representing a susceptibility factor for symptom generation. © 2011 Sciamanna et al.

Bonsi P.,Laboratory of Neurophysiology and Plasticity | Cuomo D.,University of Rome Tor Vergata | Martella G.,University of Rome Tor Vergata | Madeo G.,University of Rome Tor Vergata | And 5 more authors.
Frontiers in Neuroanatomy | Year: 2011

Work over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in the context of basal ganglia function. The recognition that these interneurons are essential in synaptic plasticity and motor learning represents a significant step ahead in deciphering how the striatum processes cortical inputs, and why pathological circumstances cause motor dysfunction. Loss of the reciprocal modulation between dopaminergic inputs and the intrinsic cholinergic innervation within the striatum appears to be the trigger for pathophysiological changes occurring in basal ganglia disorders. Accordingly, there is now compelling evidence showing profound changes in cholinergic markers in these disorders, in particular Parkinson's disease and dystonia. Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders. © 2011 Bonsi, Cuomo, Martella, Madeo, Schirinzi, Puglisi, Ponterio and Pisani.

Vanni V.,University of Rome Tor Vergata | Vanni V.,Laboratory of Neurophysiology and Plasticity | Puglisi F.,Laboratory of Neurophysiology and Plasticity | Bonsi P.,Laboratory of Neurophysiology and Plasticity | And 8 more authors.
Experimental Neurology | Year: 2015

Early-onset torsion dystonia (DYT1) is an autosomal-dominant movement disorder characterized by sustained muscle contractions and abnormal posturing. It is caused by a three base-pair deletion (δGAG) in the gene encoding the AAA+ protein torsinA, which gives rise to a loss of function mutation responsible of neuronal functional abnormalities. Symptoms typically appear during childhood, suggesting the presence of an early critical period of sensorimotor circuit susceptibility to torsinA dysfunction. Here, we identified in two different DYT1 mouse strains, heterozygous torsinA knockout mice (Tor1a+/-) and human δGAG mutant torsinA transgenic mice (hMT), the anatomical abnormalities in the cerebellum, during a critical age for synaptogenesis (postnatal day 14, P14). By means of immunofluorescence, confocal analysis and western blot quantification, we observed a reduced inhibitory input on Purkinje cells (PCs) as well as an unbalanced excitatory innervation; a significant reduction of the parallel fiber (PF) synaptic terminals and an increase of the climbing fiber (CF) inputs. Finally, in support of the in vivo results, we also provide evidence of an impaired PF synaptogenesis in a co-culture system. Of note, these alterations were rescued and in part over-compensated in the adult age in both mouse strains, suggesting that torsinA dysfunction can induce an altered maturation of cerebellar synaptic contacts. Altogether these results indicate that a loss of function of torsinA during cerebellar synaptogenesis induces important developmental alterations, that might contribute to the age-dependent susceptibility to develop dystonia in mutation carriers. © 2015 Elsevier Inc.

Discover hidden collaborations