Search bioRxiv⌕ Search

Biology subjects

Rima, S.

Publications and source records attributed to Rima, S..

3 recordsLinked to original sources

Optogenetic stimulation of primate V1 reveals local laminar and large-scale cortical networks related to perceptual phosphenes

Developing optogenetics in non-human primates (NHPs) is essential for translating its successful implementation in rodents to clinical applications in humans. However, information about how optogenetics influences the primate cortex remains limited. Here, we evaluate how optogenetic stimulation of the primate primary visual cortex (V1) affects local and large-scale network activation concerned with visual perception. To this end we injected an optogenetic construct (AAV9-hSyn-ChR2-eYFP) into the V1 cortex of four macaque monkeys (macaca mulatta) and measured the effects of optogenetic V1 stimulation using functional magnetic resonance imaging (fMRI), laminar electrophysiology, and behavioural assessment. In three macaques, blood-oxygen-dependent (BOLD) fMRI activity could be reliably elicited with optogenetic stimulation in V1 and several connected extrastriate brain areas, including V2/V3, motion-sensitive area MT and the frontal-eye-fields (FEF), in particular when pulsed stimulation at 40 Hz was applied. BOLD modulation was associated with consistent neural spiking activity measured in V1 of two macaques. More detailed analysis revealed strongest neuronal activation in layer 4B and infragranular layers, which tightly reflected the histological expression pattern of the optogenetic construct in V1. Driving this visual network proved sufficient to elicit a visual percept ( phosphene) in one macaque during a perceptual choice task. Taken together, our findings reveal the laminar and large-cortical activation pattern related to visual phosphene generation and emphasize the need for further improving optogenetic methods in NHPs as a step towards applications in humans.

neuroscience↗

The crystal structure of SnTox3 from the necrotrophic fungus Parastagonospora nodorum reveals a unique effector fold and insights into Kex2 protease processing of fungal effectors

O_LIPlant pathogens cause disease through secreted effector proteins, which act to modulate host physiology and promote infection. Typically, the sequences of effectors provide little functional information and further targeted experimentation is required. Here, we utilised a structure/function approach to study SnTox3, an effector from the necrotrophic fungal pathogen Parastagonospora nodorum, which causes cell death in wheat-lines carrying the sensitivity gene Snn3. C_LIO_LIWe developed a workflow for the production of SnTox3 in a heterologous host that enabled crystal structure determination. We show this approach can be successfully applied to effectors from other pathogenic fungi. Complementing this, an in-silico study uncovered the prevalence of an expanded subclass of effectors from fungi. C_LIO_LIThe {beta}-barrel fold of SnTox3 is a novel fold among fungal effectors. We demonstrate that SnTox3 is a pre-pro-protein and that the protease Kex2 removes the pro-domain. Our in-silico studies suggest that Kex2-processed pro-domain (designated here as K2PP) effectors are common in fungi, and we demonstrate this experimentally for effectors from Fusarium oxysporum f sp. lycopersici. C_LIO_LIWe propose that K2PP effectors are highly prevalent among fungal effectors. The identification and classification of K2PP effectors has broad implications for the approaches used to study their function in fungal virulence. C_LI

plant biology↗

Stereomotion processing in the non-human primate brain

The cortical areas that process disparity-defined motion-in-depth (i.e. cyclopean stereomotion) were characterised with functional magnetic resonance imaging in two awake, behaving macaques. The experimental protocol was similar to previous human neuroimaging studies. We contrasted the responses to dynamic random-dot patterns that continuously changed their binocular disparity over time with those to a control condition that shared the same properties, except that the temporal frames were shuffled. A whole-brain voxel-wise analysis revealed that in all four cortical hemispheres, three areas showed consistent sensitivity to cyclopean stereomotion. Two of them were localised respectively in the lower bank of the superior temporal sulcus (CSMSTS) and on the neighbouring infero-temporal gyrus (CSMITG). The third area was situated in the posterior parietal cortex (CSMPPC). Additional ROIs-based analyses within retinotopic areas defined in both animals indicated weaker but significant responses to cyclopean stereomotion within the MT cluster (most notably in areas MSTv and FST). Altogether, our results are in agreement with previous findings in both human and macaque and suggest that the cortical networks that process cyclopean stereomotion is relatively well preserved between the two primate species.

neuroscience↗