In a first set of experiments, we performed optogenetic injections into LGN of NHP. This enabled the selective targeting of so-called konio neurons and the investigation of their visual function. We found that less than 50% of these neurons were visually responsive at least under anaesthesia and that their projection to V1 influenced visual responses in V1’s supragranular layers. The results of this work are published in Klein et al (Klein et al., 2016), featured in a preview (Jazayeri and Remington, 2016). This work presents the first successful attempt to selectively target a neuronal population in NHP using optogenetics. It serves as an important first step for cell-specific manipulation of LGN function during binocular vision (Dougherty et al, J Comp Neurol, 2019; Dougherty et al, eNeuro, 2021). A second result of our publication on optogenetics was that retrograde labelling of cortico-geniculate neurons was negligible with this approach. We therefore decided for the next series of experiments to target the projection from V1 to LGN to perform optogenetic injections directly into V1 (Ortiz-Rios et al,bioRxiv,2021). We first used fMRI to measure the global brain activation pattern associated with optogenetic stimulation of V1. The results show very robust local positive BOLD activation at the site of optogenetic stimulation in the V1, and additional remote activation in few connected cortical and subcortical areas (LGN and MT). We also carried out electrophysiological multi-electrode recordings from the different layers in V1 to establish the neurophysiological correlate of the positive BOLD activation that results from optogenetic stimulation. Our results suggest that the positive BOLD signal is best explained by a layer specific V1 spiking activity. In parallel we also performed behavioural tests that demonstrated that V1 optogenetic stimulation can generate an artificial visual percept (‘phosphene’). In the course of this project, we also participated in international collaborations aimed at improving optogenetic methods in NHP before they can be translated for applications in humans (Galvan et al, J Neurosci, 2017; Tremblay et al, Neuron, 2020; Klink et al, Neuroimage, 2021).
In addition to this work on optogenetic stimulation of visual cortex, we also carried out investigations that advanced our understanding on the neuronal basis of attentional sampling and the emergence of theta (3-8 Hz) rhythmic brain activity. In a first publication we demonstrated how interactions between neighbouring neuronal populations at the visual receptive field level give rise to the emergence of theta rhythmic activity that is tightly correlated with attentional sampling (Kienitz, Current Biology, 2018). We then demonstrated in a collaboration the emergence of similar attentional sampling in humans (Chota et al, Scientific Reports, 2018). Comparing theta with gamma oscillations, we could also demonstrate how theta oscillations can serve as a feedforward signal between areas of visual cortex (Kienitz et al, Current Biology, 2021).
Neuroscience involving non-human primates (NHP) requires highest ethical and scientific standards and benefits from a collaborative approach in which resources and methods of good practice are shared in the community, with recent 3R contributions from us for refined implants (Ortiz-Rios et al, J Neurosci Meth, 2018; Perry et al, J Neurosci Meth, 2021) and to the NHP data sharing initiative (Milham et al, Neuron, 2018).
