Abstract Body

Aims: Migraine is a complex disorder characterized by altered responsivity and abnormal processing of visual information. How the known synaptic alterations characterizing migraine reverberate into these network-level dysfunctions is however still unclear.

Methods: We investigated the primary visual cortex (V1) extracellular potentials of wild-type (WT) and of a genetic rodent model of type-1-familial-hemiplegic-migraine (FHM1).

Results: We found reduced multi-unit-activity in FHM1 mice in response to high visual contrasts. The local-field-potential γ narrow band (NB, peaking at ~60 Hz) induced by low contrasts was similar in WT and in FHM1 mice. High contrasts elicited activity in the low γ ([20-55] Hz) range for WT mice as previously observed. We observed instead that such activity induced by high visual contrasts was shifted towards higher frequencies (high γ, [70-90] Hz) in FHM1 mice. However, visual information transmission was preserved.
We investigated then with a computational model the relationship between migraine-driven synaptic alterations and the experimentally observed γ-band frequency shift. Embedding the pathological synaptic alterations characterizing the model in a spiking network model of mice V1, we replicated the aforementioned experimental results. Specifically, we found the γ band frequency shift to be linked to the increase of glutamatergic cortico-cortical signaling in FHM1. Interestingly, FHM1 alterations of thalamocortical afferents compensated for the increase in cortical recurrent excitation leading to an overall decrease of the excitation/inhibition ratio.

Conclusions: These results shed light on the etiology of migraine-associated hypersensitivity to visual stimuli and might help properly tackling V1 circuitry to prevent this dysfunction.