Achiasma in humans causes gross mis-wiring of the retinal-fugal projection, resulting in overlapped cortical representations of left and right visual hemifields. We show that in areas V1-V3 this overlap is due to two co-located but non-interacting populations of neurons, each with a receptive field serving only one hemifield. Importantly, the two populations share the same local vascular control, resulting in a unique organization useful for quantifying the relationship between neural and fMRI BOLD responses without direct measurement of neural activity. Specifically, we can non-invasively double local neural responses by stimulating both neuronal populations with identical stimuli presented symmetrically across the vertical meridian to both visual hemifields, versus one population by stimulating in one hemifield. Measurements from a series of such doubling experiments show that the amplitude of BOLD response is proportional to approximately 0.5 power of the underlying neural response. Reanalyzing published data shows that this inferred relationship is general.
Human subjects: The Institutional Review Board of the University of Southern California approved the experimental protocol, and each subject provided written informed consent.
- Jody C Culham, University of Western Ontario, Canada
© 2015, Bao et al.
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De novo mutations in voltage- and ligand-gated channels have been associated with an increasing number of cases of developmental and epileptic encephalopathies, which often fail to respond to classic antiseizure medications. Here, we examine two knock-in mouse models replicating de novo sequence variations in the HCN1 voltage-gated channel gene, p.G391D and p.M153I (Hcn1G380D/+ and Hcn1M142I/+ in mouse), associated with severe drug-resistant neonatal- and childhood-onset epilepsy, respectively. Heterozygous mice from both lines displayed spontaneous generalized tonic-clonic seizures. Animals replicating the p.G391D variant had an overall more severe phenotype, with pronounced alterations in the levels and distribution of HCN1 protein, including disrupted targeting to the axon terminals of basket cell interneurons. In line with clinical reports from patients with pathogenic HCN1 sequence variations, administration of the antiepileptic Na+ channel antagonists lamotrigine and phenytoin resulted in the paradoxical induction of seizures in both mouse lines, consistent with an effect to further impair inhibitory neuron function. We also show that these variants can render HCN1 channels unresponsive to classic antagonists, indicating the need to screen mutated channels to identify novel compounds with diverse mechanism of action. Our results underscore the necessity of tailoring effective therapies for specific channel gene variants, and how strongly validated animal models may provide an invaluable tool towards reaching this objective.
Sleep and plasticity are highly interrelated, as sleep slow oscillations and sleep spindles are associated with consolidation of Hebbian-based processes. However, in adult humans, visual cortical plasticity is mainly sustained by homeostatic mechanisms, for which the role of sleep is still largely unknown. Here we demonstrate that non-REM sleep stabilizes homeostatic plasticity of ocular dominance induced in adult humans by short-term monocular deprivation: the counter-intuitive and otherwise transient boost of the deprived eye was preserved at the morning awakening (>6 hours after deprivation). Subjects exhibiting a stronger boost of the deprived eye after sleep had increased sleep spindle density in frontopolar electrodes, suggesting the involvement of distributed processes. Crucially, the individual susceptibility to visual homeostatic plasticity soon after deprivation correlated with the changes in sleep slow oscillations and spindle power in occipital sites, consistent with a modulation in early occipital visual cortex.