Saccade Modulation by Optical and Electrical Stimulation in the Macaque Frontal Eye Field

Recent studies have demonstrated that strong neural modulations can be evoked with optogenetic stimulation in macaque motor cortex without observing any evoked movements (Han et al., 2009, 2011; Diester et al., 2011). It remains unclear why such perturbations do not generate movements and if conditions exist under which they may evoke movements. In this study, we examine the effects of five optogenetic constructs in the macaque frontal eye field and use electrical microstimulation to assess whether optical perturbation of the local network leads to observable motor changes during optical, electrical, and combined stimulation. We report a significant increase in the probability of evoking saccadic eye movements when low current electrical stimulation is coupled to optical stimulation compared with when electrical stimulation is used alone. Experiments combining channelrhodopsin 2 (ChR2) and electrical stimulation with simultaneous fMRI revealed no discernible fMRI activity at the electrode tip with optical stimulation but strong activity with electrical stimulation. Our findings suggest that stimulation with current ChR2 optogenetic constructs generates subthreshold activity that contributes to the initiation of movements but, in most cases, is not sufficient to evoke a motor response

Faces in Motion: Selectivity of Macaque and Human Face Processing Areas for Dynamic Stimuli

Face recognition mechanisms need to extract information from static and dynamic faces. It has been hypothesized that the analysis of dynamic face attributes is performed by different face areas than the analysis of static facial attributes. To date, there is no evidence for such a division of labor in macaque monkeys. We used fMRI to determine specializations of macaque face areas for motion. Face areas in the fundus of the superior temporal sulcus responded to general object motion; face areas outside of the superior temporal sulcus fundus responded more to facial motion than general object motion. Thus, the macaque face-processing system exhibits regional specialization for facial motion. Human face areas, processing the same stimuli, exhibited specializations for facial motion as well. Yet the spatial patterns of facial motion selectivity differed across species, suggesting that facial dynamics are analyzed differently in humans and macaques

Accelerated neurodegeneration through chaperone-mediated oligomerization of tau

Aggregation of tau protein in the brain is associated with a class of neurodegenerative diseases known as tauopathies. FK506 binding protein 51 kDa (FKBP51, encoded by FKBP5) forms a mature chaperone complex with Hsp90 that prevents tau degradation. In this study, we have shown that tau levels are reduced throughout the brains of Fkbp5(–/–) mice. Recombinant FKBP51 and Hsp90 synergized to block tau clearance through the proteasome, resulting in tau oligomerization. Overexpression of FKBP51 in a tau transgenic mouse model revealed that FKBP51 preserved the species of tau that have been linked to Alzheimer’s disease (AD) pathogenesis, blocked amyloid formation, and decreased tangle load in the brain. Alterations in tau turnover and aggregate structure corresponded with enhanced neurotoxicity in mice. In human brains, FKBP51 levels increased relative to age and AD, corresponding with demethylation of the regulatory regions in the FKBP5 gene. We also found that higher FKBP51 levels were associated with AD progression. Our data support a model in which age-associated increases in FKBP51 levels and its interaction with Hsp90 promote neurotoxic tau accumulation. Strategies aimed at attenuating FKBP51 levels or its interaction with Hsp90 have the potential to be therapeutically relevant for AD and other tauopathies

SPARK: A US Cohort of 50,000 Families to Accelerate Autism Research

The Simons Foundation Autism Research Initiative (SFARI) has launched SPARKForAutism. org, a dynamic platform that is engaging thousands of individuals with autism spectrum disorder (ASD) and connecting them to researchers. By making all data accessible, SPARK seeks to increase our understanding of ASD and accelerate new supports and treatments for ASD