Biology subjects

Giugliano, M.

Publications and source records attributed to Giugliano, M..

3 recordsLinked to original sources

bioRxiv2018

Single-cell and neuronal network alterations in an in vitro model of Fragile X syndrome

The Fragile X mental retardation protein (FMRP) is involved in many cellular processes and it regulates synaptic and network development in neurons. Its absence is known to lead to intellectual disability, with a wide range of co-morbidities including autism. Over the past decades, FMRP research focused on abnormalities both in glutamatergic and GABAergic signalling, and an altered balance between excitation and inhibition has been hypothesised to underlie the clinical consequences of absence of the protein. Using FMRP knockout mice, we studied an in vitro model of cortical microcircuitry and observed that the loss of FMRP largely affected the electrophysiological correlates of network development and maturation but caused less alterations in single-cell phenotypes. Using a mathematical model, we demonstrated that the combination of an increased excitation and reduced inhibition describes best predicts our experimental observations during the ex vivo formation of the network connections.

neuroscience↗

bioRxiv2018

A cellular basis of human intelligence

It is generally assumed that human intelligence relies on efficient processing by neurons in our brain. Behavioral and brain-imaging studies robustly show that higher intelligence associates with faster reaction times and thicker gray matter in temporal and frontal cortical areas. However, no direct evidence exists that links individual neuron activity and structure to human intelligence. Since a large part of cortical grey matter consists of dendrites, these structures likely determine cortical architecture. In addition, dendrites strongly affect functional properties of neurons, including action potential speed. Thereby, dendritic size and action potential firing may constitute variation in cortical thickness, processing speed, and ultimately IQ.\n\nTo investigate this, we took advantage of brain tissue available from neurosurgery and recorded from pyramidal neurons in the medial temporal cortex, an area showing high association between cortical thickness, cortical activity and intelligence. Next, we reconstructed full dendritic structures of recorded neurons and combined these with brain-imaging data and IQ scores from the same subjects. We find that high IQ scores and large temporal cortical thickness associate with larger, more complex dendrites of human pyramidal neurons. We show in silico that larger dendrites enable pyramidal neurons to track activity of synaptic inputs with higher temporal precision, due to fast action potential initiation. Finally, we find that human pyramidal neurons of individuals with higher IQ scores sustain faster action potentials during repeated firing. These findings provide first evidence that human intelligence is associated with neuronal complexity, action potential speed and efficient information transfer in cortical neurons.

neuroscience↗

bioRxiv2018

The Effect of Acute Pharmacological Inhibition of Urokinase Plasminogen Activator and Neuropsin Extracellular Proteases on Neuronal Networks in vitro

Neuronal networks are surrounded by the extracellular matrix (ECM), which functions both as a scaffold and as a regulator of neuronal function. The ECM is in turn dynamically altered through the action of serine proteases, which break down its constituents. This pathway has been implicated in the regulation of synaptic plasticity and of intrinsic excitability. Here, we determined the effects of acutely inhibiting two important regulators of the ECM, Urokinase Plasminogen Activator and Neuropsin, selectively and potently with the inhibitor UAMC-01162. Spontaneous electrophysiological activity was recorded from in vitro primary rat cortical cultures using microelectrode arrays. While inhibition at a low dosage had no significant effect, at elevated concentrations network bursting dynamics and functional connectivity were drastically altered. These results indicate that the serine protease inhibition affects neuronal and synaptic properties, likely through their actions on the ECM. We propose that in the acute phase, a transient increase of excitatory synaptic efficacy is compensated for by a downregulation of single-cell excitability.

neuroscience↗