Technologies for silencing the electrical activity of genetically targeted neurons in the brain are important for assessing the contribution of specific cell types and pathways toward behaviors and pathologies. Recently we found that archaerhodopsin-3 from Halorubrum sodomense (Arch), a light-driven outward proton pump, when genetically expressed in neurons, enables them to be powerfully, transiently, and repeatedly silenced in response to pulses of light. Because of the impressive characteristics of Arch, we explored the optogenetic utility of opsins with high sequence homology to Arch, from archaea of the Halorubrum genus. We found that the archaerhodopsin from Halorubrum strain TP009, which we named ArchT, could mediate photocurrents of similar maximum amplitude to those of Arch (∼900 pA in vitro), but with a >3-fold improvement in light sensitivity over Arch, most notably in the optogenetic range of 1–10 mW/mm2, equating to >2× increase in brain tissue volume addressed by a typical single optical fiber. Upon expression in mouse or rhesus macaque cortical neurons, ArchT expressed well on neuronal membranes, including excellent trafficking for long distances down neuronal axons. The high light sensitivity prompted us to explore ArchT use in the cortex of the rhesus macaque. Optical perturbation of ArchT-expressing neurons in the brain of an awake rhesus macaque resulted in a rapid and complete (∼100%) silencing of most recorded cells, with suppressed cells achieving a median firing rate of 0 spikes/s upon illumination. A small population of neurons showed increased firing rates at long latencies following the onset of light stimulation, suggesting the existence of a mechanism of network-level neural activity balancing. The powerful net suppression of activity suggests that ArchT silencing technology might be of great use not only in the causal analysis of neural circuits, but may have therapeutic applications.
FMRI studies have revealed three scene-selective regions in human visual cortex (the Parahippocampal Place Area (PPA), Transverse Occipital Sulcus (TOS) and RetroSplenial Cortex (RSC)), which have been linked to higher-order functions such as navigation, scene perception/recognition, and contextual association. Here, we document corresponding (presumptively homologous) scene-selective regions in the awake macaque monkey, based on direct comparison to human maps, using identical stimuli and largely overlapping fMRI procedures. In humans, our results showed that the three scene-selective regions are centered near - but distinct from - the gyri/sulci for which they were originally named. In addition, all these regions are located within or adjacent to known retinotopic areas. Human RSC and PPA are located adjacent to the peripheral representation of primary and secondary visual cortex, respectively. Human TOS is located immediately anterior/ventral to retinotopic area V3A, within retinotopic regions LO-1, V3B, and/or V7. Mirroring the arrangement of human regions FFA and PPA (which are adjacent to each other in cortex), the presumptive monkey homologue of human PPA is located adjacent to the monkey homologue of human FFA, near the posterior superior temporal sulcus. Monkey TOS includes the region predicted from the human maps (macaque V4d), extending into retinotopically-defined V3A. A possible monkey homologue of human RSC lies in the medial bank, near peripheral V1. Overall, our findings suggest a homologous neural architecture for scene-selective regions in visual cortex of humans and non-human primates, analogous to the face-selective regions demonstrated earlier in these two species.
Increasing evidence suggests that primate visual cortex has a specialized architecture for processing discrete object categories such as faces. Human fMRI studies have described a localized region in the fusiform gyrus [the fusiform face area (FFA)] that responds selectively to faces. In contrast, in nonhuman primates, electrophysiological and fMRI studies have instead revealed 2 apparently analogous regions of face representation: the posterior temporal face patch (PTFP) and the anterior temporal face patch (ATFP). An earlier study suggested that human FFA is homologous to the PTFP in macaque. However, in humans, no obvious homologue of the macaque ATFP has been demonstrated. Here, we used fMRI to map face-selective sites in both humans and macaques, based on equivalent stimuli in a quantitative topographic comparison. This fMRI evidence suggests that such a face-selective area exists in human anterior inferotemporal cortex, comprising the apparent homologue of the fMRI-defined ATFP in macaques.face processing ͉ fMRI ͉ inferotemporal cortex ͉ macaque-human homology T he fusiform face area (FFA) is one of the most distinctive regions in the human ventral temporal cortex. A wide range of noninvasive techniques, including PET, fMRI, ERP, and MEG have shown that FFA responds selectively to images of faces, relative to a wide variety of control objects (1-7). Such approaches have revealed an enormous amount about face selectivity in this distinctive region of human cerebral cortex.Such noninvasive techniques cannot furnish the kind of incisive information that is available from classical neurobiological techniques (e.g., single-unit recording) in nonhuman primates. These 2 realms have begun to be bridged by recent fMRI studies in awake monkeys, which demonstrated that apparently homologous face-selective regions also exist in macaque inferotemporal (IT) cortex (8,9). Subsequent experiments reported that Ϸ97% of the single units in the largest face-selective region (the so-called posterior temporal face patch, located in caudal TE) respond strongly and selectively to images of faces, compared with images of control objects (10). This fMRI and physiological evidence supports the idea that this region of monkey cortex is indeed selective for faces.A computational transformation concluded that this posterior temporal face patch (PTFP) in macaques is located in a cortical region that corresponds topographically to area FFA in human subjects (8). This analysis assumes that neighborhood relations between specific cortical areas are evolutionarily conserved across the sheet of cortical gray matter, as validated in many previous human-monkey comparisons (11-14).However, this conclusion raises a significant issue. In macaques, an additional face-selective region is consistently found further anterior in the temporal lobe, in rostral TE (8-10, 15, 16); here, this is termed the anterior temporal face patch (ATFP). However, in humans, no such area (i.e., anterior to FFA) has been reported by conventional fMRI mapping of face rep...
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