Tiziana Sacco

Bio: Tiziana Sacco is an academic researcher from University of Turin. The author has contributed to research in topics: Amygdala & Auditory cortex. The author has an hindex of 14, co-authored 18 publications receiving 1030 citations. Previous affiliations of Tiziana Sacco include University of Perugia.

Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28

Abstract: Autosomal dominant spinocerebellar ataxias (SCAs) are genetically heterogeneous neurological disorders characterized by cerebellar dysfunction mostly due to Purkinje cell degeneration. Here we show that AFG3L2 mutations cause SCA type 28. Along with paraplegin, which causes recessive spastic paraplegia, AFG3L2 is a component of the conserved m-AAA metalloprotease complex involved in the maintenance of the mitochondrial proteome. We identified heterozygous missense mutations in five unrelated SCA families and found that AFG3L2 is highly and selectively expressed in human cerebellar Purkinje cells. m-AAA-deficient yeast cells expressing human mutated AFG3L2 homocomplex show respiratory deficiency, proteolytic impairment and deficiency of respiratory chain complex IV. Structure homology modeling indicates that the mutations may affect AFG3L2 substrate handling. This work identifies AFG3L2 as a novel cause of dominant neurodegenerative disease and indicates a previously unknown role for this component of the mitochondrial protein quality control machinery in protecting the human cerebellum against neurodegeneration.

Role of secondary sensory cortices in emotional memory storage and retrieval in rats.

Abstract: Visual, acoustic, and olfactory stimuli associated with a highly charged emotional situation take on the affective qualities of that situation. Where the emotional meaning of a given sensory experience is stored is a matter of debate. We found that excitotoxic lesions of auditory, visual, or olfactory secondary sensory cortices impaired remote, but not recent, fear memories in rats. Amnesia was modality-specific and not due to an interference with sensory or emotional processes. In these sites, memory persistence was dependent on ongoing protein kinase Mzeta activity and was associated with an increased activity of layers II-IV, thus suggesting a synaptic strengthening of corticocortical connections. Lesions of the same areas left intact the memory of sensory stimuli not associated with any emotional charge. We propose that secondary sensory cortices support memory storage and retrieval of sensory stimuli that have acquired a behavioral salience with the experience.

Reversible inactivation of amygdala and cerebellum but not perirhinal cortex impairs reactivated fear memories

Abstract: The cerebellum, amygdala and perirhinal cortex are involved in fear learning but the different roles that these three structures play in aversive learning are not well defined. Here we show that in adult rats amygdala or cerebellar vermis blockade causes amnesia when performed immediately, but not 1 h, after the recall of fear memories. Thus, the cerebellum, as well as the amygdala, influences long-term fear memories. These effects are long lasting, as they do not recover over time, even after a reminder shock administration. However, all of the subjects were able to form new fear memories in the absence of inactivation. By increasing the strength of conditioning, we observed that stronger fear memories are affected by the combined but not independent amygdala and cerebellar blockade. These results demonstrate that the cerebellum supports the memory processes even in the absence of a crucial site for emotions like the amygdala. Furthermore, they suggest that the amygdala is only one of the neural sites underlying long-term fear memories. Finally, the inactivation of the perirhinal cortex never alters retrieved fear traces, showing important differences between the amygdala, cerebellum and perirhinal cortex in emotional memories.

Functional Roles of an ERG Current Isolated in Cerebellar Purkinje Neurons

Abstract: Transcripts encoding ERG potassium channels are expressed by most neurons of the CNS. By patch-clamp whole cell recording from Purkinje neurons in slices of young (5–9 days old) mouse cerebellum we...

Learning and Memory

Abstract: Experimental Psychology Its Scope and Method. IV. Learning and Memory. By Jean-Francois Le Ny, G. De Montpellier, G. Oleron and Cesar Flores. Translated by Louise Elkington. Edited by P. Fraisse and Jean Piaget. Pp. viii + 376. (Routledge and Kegan Paul: London, April 1970.) 80s.

A new pathway for mitochondrial quality control: mitochondrial‐derived vesicles

Abstract: The last decade has been marked by tremendous progress in our understanding of the cell biology of mitochondria, with the identification of molecules and mechanisms that regulate their fusion, fission, motility, and the architectural transitions within the inner membrane. More importantly, the manipulation of these machineries in tissues has provided links between mitochondrial dynamics and physiology. Indeed, just as the proteins required for fusion and fission were identified, they were quickly linked to both rare and common human diseases. This highlighted the critical importance of this emerging field to medicine, with new hopes of finding drugable targets for numerous pathologies, from neurodegenerative diseases to inflammation and cancer. In the midst of these exciting new discoveries, an unexpected new aspect of mitochondrial cell biology has been uncovered; the generation of small vesicular carriers that transport mitochondrial proteins and lipids to other intracellular organelles. These mitochondrial-derived vesicles (MDVs) were first found to transport a mitochondrial outer membrane protein MAPL to a subpopulation of peroxisomes. However, other MDVs did not target peroxisomes and instead fused with the late endosome, or multivesicular body. The Parkinson's disease-associated proteins Vps35, Parkin, and PINK1 are involved in the biogenesis of a subset of these MDVs, linking this novel trafficking pathway to human disease. In this review, we outline what has been learned about the mechanisms and functional importance of MDV transport and speculate on the greater impact of these pathways in cellular physiology.

Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder.

Abstract: Context Little is known about the neural abnormalities underlying generalized anxiety disorder (GAD). Studies in other anxiety disorders have implicated the amygdala, but work in GAD has yielded conflicting results. The amygdala is composed of distinct subregions that interact with dissociable brain networks, which have been studied only in experimental animals. A functional connectivity approach at the subregional level may therefore yield novel insights into GAD. Objectives To determine whether distinct connectivity patterns can be reliably identified for the basolateral (BLA) and centromedial (CMA) subregions of the human amygdala, and to examine subregional connectivity patterns and potential compensatory amygdalar connectivity in GAD. Design Cross-sectional study. Setting Academic medical center. Participants Two cohorts of healthy control subjects (consisting of 17 and 31 subjects) and 16 patients with GAD. Main Outcome Measures Functional connectivity with cytoarchitectonically determined BLA and CMA regions of interest, measured during functional magnetic resonance imaging performed while subjects were resting quietly in the scanner. Amygdalar gray matter volume was also investigated with voxel-based morphometry. Results Reproducible subregional differences in large-scale connectivity were identified in both cohorts of healthy controls. The BLA was differentially connected with primary and higher-order sensory and medial prefrontal cortices. The CMA was connected with the midbrain, thalamus, and cerebellum. In GAD patients, BLA and CMA connectivity patterns were significantly less distinct, and increased gray matter volume was noted primarily in the CMA. Across the subregions, GAD patients had increased connectivity with a previously characterized frontoparietal executive control network and decreased connectivity with an insula- and cingulate-based salience network. Conclusions Our findings provide new insights into the functional neuroanatomy of the human amygdala and converge with connectivity studies in experimental animals. In GAD, we find evidence of an intra-amygdalar abnormality and engagement of a compensatory frontoparietal executive control network, consistent with cognitive theories of GAD.