Papers by Marco Cambiaghi
Journal of Neurology, Apr 18, 2015
Most papers studying emotional learning and emotion-related disorders are mainly based on the exp... more Most papers studying emotional learning and emotion-related disorders are mainly based on the experiments per-formed by the famous Russian physiologist Ivan Pavlov more than a century ago. Nowadays, we reflexively link his name to a dinging bell and a drooling dog, although he never trained a dog to salivate to the sound of a bell [8]. Our brains have been conditioned with the myth, as stated by George Johnson in The New York Times (December, 2014). However, this is just a very small fraction of Pavlov's researches and his life.
The recall of fear memory recruits theta activity in the secondary auditory cortex at recent and remote time-points
Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams
iScience
Frontiers in Neuroscience, Apr 6, 2023
Developmental and epileptic encephalopathies are childhood syndromes of severe epilepsy associate... more Developmental and epileptic encephalopathies are childhood syndromes of severe epilepsy associated with cognitive and behavioral disorders. Of note, epileptic seizures represent only a part, although substantial, of the clinical spectrum. Whether the epileptiform activity per se accounts for developmental and intellectual disabilities is still unclear. In a few cases, seizures can be alleviated by antiseizure medication (ASM). However, the major comorbid features associated remain unsolved, including psychiatric disorders such as autism-like and attention deficit hyperactivity disorder-like behavior. Not surprisingly, the number of genes known to be involved is continuously growing, and genetically engineered rodent models are valuable tools for investigating the impact of gene mutations on local and distributed brain circuits. Despite the inconsistencies and problems arising in the generation and validation of the different preclinical models, those are unique and precious tools to identify new molecular targets, and essential to provide prospects for effective therapeutics. KEYWORDS epilepsy, rodent models, therapeutics, adeno-associated virus, rare diseases A large battery of genes, epigenetic changes, and environmental factors such as pollutants, diet, or brain injuries are key factors that modify brain circuits to generate epileptic disorders that involve multiple interconnected brain regions for epilepsy onset and development (Figure ). Brain modifications may result in the alteration of the fine balance between excitation and inhibition (E/I balance; Figure ), and a seizure can arise in different brain areas and further spreads to other synaptically-connected brain regions, increasing its severity (Figure ). Worldwide, the prevalence of epileptic diseases is classified into common and rare epilepsies, representing ~95 and ~5%, respectively. Developmental and epileptic encephalopathies (DEEs) are rare diseases (Figure ) and comprise a large, heterogeneous group of devastating epileptic disorders occurring in pediatric age. Those are mainly characterized by pharmaco-resistant polymorphous epilepsy, severe electroencephalogram (EEG) abnormalities, and developmental regression . Patients experience a broad spectrum of neuropsychiatric symptoms ranging from less to more severe, including neurological impairments, intellectual disability, sensory and communication deficits, and other significant psychiatric, motor, and behavioral alterations. DEEs are caused by various factors, among which 30-50% is genetic in origin,
Nature Communications
The adult brain retains over life endogenous neural stem/precursor cells (eNPCs) within the subve... more The adult brain retains over life endogenous neural stem/precursor cells (eNPCs) within the subventricular zone (SVZ). Whether or not these cells exert physiological functions is still unclear. In the present work, we provide evidence that SVZ-eNPCs tune structural, electrophysiological, and behavioural aspects of striatal function via secretion of insulin-like growth factor binding protein-like 1 (IGFBPL1). In mice, selective ablation of SVZ-eNPCs or selective abrogation of IGFBPL1 determined an impairment of striatal medium spiny neuron morphology, a higher failure rate in GABAergic transmission mediated by fast-spiking interneurons, and striatum-related behavioural dysfunctions. We also found IGFBPL1 expression in the human SVZ, foetal and induced-pluripotent stem cell-derived NPCs. Finally, we found a significant correlation between SVZ damage, reduction of striatum volume, and impairment of information processing speed in neurological patients. Our results highlight the physiol...
Translational psychiatry, Jan 10, 2016
Cognitive processing is highly dependent on the functional integrity of gamma-amino-butyric acid ... more Cognitive processing is highly dependent on the functional integrity of gamma-amino-butyric acid (GABA) interneurons in the brain. These cells regulate excitability and synaptic plasticity of principal neurons balancing the excitatory/inhibitory tone of cortical networks. Reduced function of parvalbumin (PV) interneurons and disruption of GABAergic synapses in the cortical circuitry result in desynchronized network activity associated with cognitive impairment across many psychiatric disorders, including schizophrenia. However, the mechanisms underlying these complex phenotypes are still poorly understood. Here we show that in animal models, genetic deletion of fibroblast growth factor 14 (Fgf14), a regulator of neuronal excitability and synaptic transmission, leads to loss of PV interneurons in the CA1 hippocampal region, a critical area for cognitive function. Strikingly, this cellular phenotype associates with decreased expression of glutamic acid decarboxylase 67 (GAD67) and ves...
Journal of Neurology, Mar 16, 2017
The current way of thinking in neuroanatomy, and also in neurology, owes much to a Renaissance ph... more The current way of thinking in neuroanatomy, and also in neurology, owes much to a Renaissance physician who literally shook up the world of anatomy and broke centuries-old dogma that crippled the evolution of medicine. It was indeed during the first half of the 16 th century when Vesalius introduced the modern concept of studying and teaching anatomy, centering his anatomical descriptions on personal and direct observation. The brain and the nervous system were fascinating to Vesalius, whose functional unit, however, he did not totally grasp, in particular with regard to the role of the ventricles as compared with grey and white matter. Andreas Vesalius (the latin name of Andries Wytinck van Wesel) was born on December 31, 1514 in Rue de Minimes, in the neighbourhood of Sablon, an area just south of the ramparts of Brussels, Belgium, then part of the Holy Roman Empire. His father Andries, as at least the four generations preceding him, was at the service of the Roman royalty, so it was his mother Isabella Crabbe that tended to Andreas's early education . Close to the house where he lived, on Gallows Hill, the young Vesalius often had the opportunity to approach the dead bodies of executed criminals. This was probably one of the reasons that influenced his decision to study medicine. After elementary studies in Brussels, at 15 years old he matriculated at the University of Louvain on February 25, 1530. The Castle College was the same where his father studied before and his brother Franciscus after him . Here, he had the possibility to study not only Latin but also Greek and Hebrew, which later allowed him to access and compare original anatomical texts . Vesalius completed his studies within three years and in the summer of 1533 he moved at the University of Paris. Most of the texts, here, were based on the works of Galen of Pergamon (129/130 AD-210/216 AD), who represented the undisputed authority in anatomical teaching. However, due to the Roman law which prohibited corpse dissection (lex de sepulcris), Galen could perform his observations only in animals [2, 3]. Among his teachers, Vesalius had Jacobus Sylvius (1478-1555) and Johann Guenther von Andernach (1505-1574), who adopted the traditional way of teaching anatomy during dissection: the lector (reader) seated on an elevated chair was the professor reading Galen's texts, the ostensor (demonstrator) indicated the anatomical structures mentioned by the reader, and finally the sector (dissector) was the barber-surgeon who performed the dissection at the anatomical table. Thanks to his enthusiasm Vesalius was often asked to act as the barber-surgeon, a great privilege for a 18-year old student. This helped him training in the art of dissection, learning directly and not just reading old texts . Being the son of the Emperor's apothecary, at the outbreak of the war in France in July 1536, Vesalius was forced to escape from Paris before graduating. He completed his dissertation in Leuven in 1537 and thanks to his connections with influential officials he was authorized to
From Aldini's galvanization of human bodies to the Modern Prometheus
During the 18th century the perception of electricity was significantly different from was it is ... more During the 18th century the perception of electricity was significantly different from was it is today. In particular, the idea of ‘bioelectricity’ - the electrical phenomena that control our body - was trying to surface among a set of multifaceted studies and innovative processes involving electricity. The concept of animal electricity finally emerged at the very end of the 18th century thanks to the work of the Italian physician, physicist and anatomist at the University of Bologna, Luigi Galvani, whose findings were disputed by the physicist Alessandro Volta, from Como. At the beginning of the 19th century, Giovanni Aldini, the nephew of Galvani, attempted to demonstrate the existence of animal electricity by using voltaic batteries to stimulate the corpse of animals and humans, often in front of laypersons. One of these public events occurred in London on January 17, 1803, when Aldini applied electrical stimulation (at that time called Galvanic stimulation) on the corpse of a ha...
Biomolecules
Early stroke therapeutic approaches rely on limited options, further characterized by a narrow th... more Early stroke therapeutic approaches rely on limited options, further characterized by a narrow therapeutic time window. In this context, the application of transcranial direct current stimulation (tDCS) in the acute phases after brain ischemia is emerging as a promising non-invasive tool. Despite the wide clinical application of tDCS, the cellular mechanisms underlying its positive effects are still poorly understood. Here, we explored the effects of cathodal tDCS (C-tDCS) 6 h after focal forelimb M1 ischemia in Cx3CR1GFP/+ mice. C-tDCS improved motor functionality of the affected forelimb, as assessed by the cylinder and foot-fault tests at 48 h, though not changing the ischemic volume. In parallel, histological analysis showed that motor recovery is associated with decreased microglial cell density in the area surrounding the ischemic core, while astrocytes were not affected. Deeper analysis of microglia morphology within the perilesional area revealed a shift toward a more ramifi...
New Protocol for Auditory Brainstem Implant Positioning
Neuroscience and Neurological Surgery
Background: Surgery for applying the auditory brainstem implant is an otoneurosurgery that requir... more Background: Surgery for applying the auditory brainstem implant is an otoneurosurgery that requires careful intraoperative monitoring to optimize the placement of the electrode paddle. This study aimed to validate a new method capable of increasing the accuracy of electrode array placement, reducing channel interaction, electrical artefacts, and saturation effects, and providing the largest number of electrodes that can be activated with the lowest possible electric charge. Materials and methods: Thirty-six subjects aged between 1.42 and 69.92 years were tested during surgery for auditory brainstem implantation. We recorded auditory electrical responses of the brainstem using the implant supplier's suggested stimulation protocol and the new protocol. Results: Saturations effects and electric artefacts were noticed respectively in 81.85% and 53.25% of recordings using implant supplier's method, while in 70.34% and 24.75% of recordings using the new method, with a percentage v...
High-frequency repetitive transcranial magnetic stimulation enhances layer II/III morphological dendritic plasticity in mouse primary motor cortex
Behavioural Brain Research, 2021
High-frequency repeated transcranial magnetic stimulation (HF-rTMS) is a safe non-invasive neurom... more High-frequency repeated transcranial magnetic stimulation (HF-rTMS) is a safe non-invasive neuromodulatory technique and there is a body of evidence shows that it can modulate plasticity in different brain areas. One of the most interesting application of HF-rTMS is the modulation of plasticity in primary motor cortex (M1) to promote recovery after brain injuries. However, the underlying mechanism by which HF-rTMS modulates motor cortex plasticity remain to be investigated. In this study, we investigated the effects of HF-rTMS treatment on morphological plasticity of pyramidal neurons in layer II/III (L2/3) of the primary motor cortex in mice. Our results show that the treatment did not increase anxiety in mice in the open field test and the elevated plus-maze test. Treated mice displayed increased total spine density in apical and basal dendrites, with a predominance of thin spines. The treatment also increased dendritic complexity, as assessed by Sholl analysis at both apical and ...
Neural circuitry of long-term fear memories
Neuroscience and Neurological Surgery, 2021
Background: Surgery for applying the auditory brainstem implant is an otoneurosurgery that requir... more Background: Surgery for applying the auditory brainstem implant is an otoneurosurgery that requires careful intraoperative monitoring to optimize the placement of the electrode paddle. This study aimed to validate a new method capable of increasing the accuracy of electrode array placement, reducing channel interaction, electrical artefacts, and saturation effects, and providing the largest number of electrodes that can be activated with the lowest possible electric charge. Materials and methods: Thirty-six subjects aged between 1.42 and 69.92 years were tested during surgery for auditory brainstem implantation. We recorded auditory electrical responses of the brainstem using the implant supplier's suggested stimulation protocol and the new protocol. Results: Saturations effects and electric artefacts were noticed respectively in 81.85% and 53.25% of recordings using implant supplier's method, while in 70.34% and 24.75% of recordings using the new method, with a percentage v...
Value coding neurons in lateral amygdala are recruited by both unconditioned and learned emotional stimuli
The crosstalk within theta rhythms between secondary auditory cortex and basolateral amygdala is essential during fear memory recall
Reversal inactivation of Te2 impairs remote fear memory and BLA learned-plasticity
The assignment of the affective/motivational value to sensory stimuli is mediated by the Te2 cortex
Treating neurologic disorders with noninvasive brain stimulation techniques has always been one o... more Treating neurologic disorders with noninvasive brain stimulation techniques has always been one of the major goals of neurophysiology and to a broad extent, of modern neurology and psychiatry. The first attempts date back at least to 50 AD, when the Roman physician Scribonius Largus used electric currents from torpedo fishes to treat headaches. Unfortunately, these initial efforts sank into oblivion until the 18th century. In the last 2 decades, thanks to technological improvements, noninvasive transcranial stimulation is re-emerging as an appealing and promising approach to be used in different fields of neurology and neuroscience, with the number of related publications increasing exponentially in both clinical and basic science studies. This new age is particularly due to the broad-spectrum use of 2 techniques called transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Despite the undoubted importance of conventional brain stimulation method...
Gaude, Silvia Mari, Stefano Sandrone, Marco Cursi, Luis Teneud, Giancarlo Comi, Giovanna Luca Per... more Gaude, Silvia Mari, Stefano Sandrone, Marco Cursi, Luis Teneud, Giancarlo Comi, Giovanna Luca Peruzzotti-Jametti, Marco Cambiaghi, Marco Bacigaluppi, Mattia Gallizioli, Edoardo Ischemic Stroke Safety and Efficacy of Transcranial Direct Current Stimulation in Acute Experimental Print ISSN: 0039-2499. Online ISSN: 1524-4628 Copyright © 2013 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Stroke published online August 27, 2013; Stroke. http://stroke.ahajournals.org/content/early/2013/08/27/STROKEAHA.113.001687 World Wide Web at: The online version of this article, along with updated information and services, is located on the http://stroke.ahajournals.org/content/suppl/2013/08/27/STROKEAHA.113.001687.DC1.html Data Supplement (unedited) at:
Spontaneous and odor-evoked seizures in Synapsin I/II/III knockout mice: Electrophysiological characterization
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Papers by Marco Cambiaghi