Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution

The quest to determine how precise neural activity patterns mediate computation, behavior, and pathology would be greatly aided by a set of tools for reliably activating and inactivating genetically targeted neurons, in a temporally precise and rapidly reversible fashion. Having earlier adapted a light-activated cation channel, channelrhodopsin-2 (ChR2), for allowing neurons to be stimulated by blue light, we searched for a complementary tool that would enable optical neuronal inhibition, driven by light of a second color. Here we report that targeting the codon-optimized form of the light-driven chloride pump halorhodopsin from the archaebacterium Natronomas pharaonis (hereafter abbreviated Halo) to genetically-specified neurons enables them to be silenced reliably, and reversibly, by millisecond-timescale pulses of yellow light. We show that trains of yellow and blue light pulses can drive high-fidelity sequences of hyperpolarizations and depolarizations in neurons simultaneously expressing yellow light-driven Halo and blue light-driven ChR2, allowing for the first time manipulations of neural synchrony without perturbation of other parameters such as spiking rates. The Halo/ChR2 system thus constitutes a powerful toolbox for multichannel photoinhibition and photostimulation of virally or transgenically targeted neural circuits without need for exogenous chemicals, enabling systematic analysis and engineering of the brain, and quantitative bioengineering of excitable cells

Decreased hippocampal volume, indirectly measured, is associated with depressive symptoms and consolidation deficits in multiple sclerosis

Item does not contain fulltextBackground: The human hippocampus plays a role in episodic memory and depression. Recently, it has been shown, using manual tracings, that the hippocampus is smaller in volume in MS patients compared with healthy controls, and that, at least for depression, hippocampal atrophy correlates with symptom severity. Methods: Because manual tracing of the hippocampus is time consuming, we used a semi-automatic procedure for temporal horn volumetry in 72 multiple sclerosis (MS) patients and 16 control subjects as an indirect measure of hippocampal volume. We analysed memory performance with the California Verbal Learning Test (using separate indices for encoding, consolidation and retrieval) and depressive mood with the Beck’s Depression Inventory (distinguishing between psychic and somatic aspects). Results: MS patients had significantly larger temporal horn volumes and volume correlated with psychic symptoms of depressive mood. Temporal horn volume was also associated with consolidation, in particular in the most impaired group. Conclusions: Temporal horn volume can be measured relatively easily and appears to correlate with two major clinical problems in MS patients: memory performance and depressive mood. The link between temporal horn volume, consolidation and depression may be hippocampal atrophy, as suggested by their adjacent neuroanatomical localization, and by the similarity in functional loss following impairment of these two structures.10 p