Synaptic alterations in visual cortex reshape contrast-dependent gamma oscillations and inhibition-excitation ratio in a genetic mouse model of migraine

The Journal of Headache and Pain - Tập 23 - Trang 1-18 - 2022
Nicolò Meneghetti1,2, Chiara Cerri3,4,5, Eleonora Vannini3,4, Elena Tantillo3,6,7, Angelita Tottene8, Daniela Pietrobon8,9,10, Matteo Caleo3,8,9, Alberto Mazzoni1,2
1The Biorobotics Institute, Scuola Superiore Sant’Anna, Pisa, Italy
2Department of Excellence for Robotics and AI, Scuola Superiore Sant’Anna, Pisa, Italy
3Neuroscience Institute, National Research Council (CNR), Pisa, Italy
4Fondazione Umberto Veronesi, Milan, Italy
5Department of Pharmacy, University of Pisa, Pisa, Italy
6Fondazione Pisana per la Scienza Onlus (FPS), Pisa, Italy
7Scuola Normale Superiore, Pisa, Italy
8Department of Biomedical Sciences, University of Padova, Padova, Italy
9Padova Neuroscience Center, University of Padova, Padova, Italy
10CNR Institute of Neuroscience, Padova, Italy

Tóm tắt

Migraine affects a significant fraction of the world population, yet its etiology is not completely understood. In vitro results highlighted thalamocortical and intra-cortical glutamatergic synaptic gain-of-function associated with a monogenic form of migraine (familial-hemiplegic-migraine-type-1: FHM1). However, how these alterations reverberate on cortical activity remains unclear. As altered responsivity to visual stimuli and abnormal processing of visual sensory information are common hallmarks of migraine, herein we investigated the effects of FHM1-driven synaptic alterations in the visual cortex of awake mice. We recorded extracellular field potentials from the primary visual cortex (V1) of head-fixed awake FHM1 knock-in (n = 12) and wild type (n = 12) mice in response to square-wave gratings with different visual contrasts. Additionally, we reproduced in silico the obtained experimental results with a novel spiking neurons network model of mouse V1, by implementing in the model both the synaptic alterations characterizing the FHM1 genetic mouse model adopted. FHM1 mice displayed similar amplitude but slower temporal evolution of visual evoked potentials. Visual contrast stimuli induced a lower increase of multi-unit activity in FHM1 mice, while the amount of information content about contrast level remained, however, similar to WT. Spectral analysis of the local field potentials revealed an increase in the β/low γ range of WT mice following the abrupt reversal of contrast gratings. Such frequency range transitioned to the high γ range in FHM1 mice. Despite this change in the encoding channel, these oscillations preserved the amount of information conveyed about visual contrast. The computational model showed how these network effects may arise from a combination of changes in thalamocortical and intra-cortical synaptic transmission, with the former inducing a lower cortical activity and the latter inducing the higher frequencies ɣ oscillations. Contrast-driven ɣ modulation in V1 activity occurs at a much higher frequency in FHM1. This is likely to play a role in the altered processing of visual information. Computational studies suggest that this shift is specifically due to enhanced cortical excitatory transmission. Our network model can help to shed light on the relationship between cellular and network levels of migraine neural alterations.

Tài liệu tham khảo

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