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Optogenetic investigation of cortical layer-6 neuron contributions to dynamic visual perception

Periodic Reporting for period 3 - OptoVision (Optogenetic investigation of cortical layer-6 neuron contributions to dynamic visual perception)

Reporting period: 2018-12-01 to 2020-05-31

In order to achieve a more complete understanding of neocortical brain function in health and disease, we need to delineate the computations of specific cell populations and how they dynamically exert their impact on connected target neurons. Here we’ve targeted neurons in the lateral geniculate nucleus (LGN) and in primary visual cortex (V1) using modern optogenetic methods that allow selective activation of neurons in the presence of light. Combining optogenetic stimulation with functional magnetic resonance imaging enables us to delineate the large scale cortical and subcortical connectivity of optogenetic activation. By assessing the electrophysiological activation we are able to characterize how this is locally reflected at the level of single neurons or synaptic activation patterns in the different layers of cortex. These assessments of neural function at the meso- and macro-scale are accompanied by behavioural assessment to what extent optogenetically evoked activation patterns can evoke visual phosphenes or bias visually based behaviour. By delineating the neural mechanisms by which optogenetic activation creates or modifies visual behaviour, our work is a first step towards building an optogenetics based prosthetic device that aims to improve vision under conditions of blindness.
For a first set of experiments, we performed optogenetic injections into LGN. 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 by Jazayeri(Jazayeri and Remington, 2016). This work presents the first successful attempt to selectively target a neuronal population in monkeys using optogenetics. A second result of this publication 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. 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 weak focal activation in few connected cortical and subcortical areas (LGN and MT). We are currently performing 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. Preliminary results suggest that the positive BOLD signal is best explained by an increase in spiking activity and gamma oscillations. In parallel we are testing to what extent the optogenetic stimulation can induce an artificial visual percept (‘phosphene’) or can serve as a gain to increase spatial attention. Preliminary results do not show a significant effect on behaviour. The interim results of these optogenetic experiments in V1 will be presented during the Society for Neuroscience meeting 2018 in San Diego and during an NIH genetic technologies workshop.
Previous work on optogenetic activation of primary visual cortex (V1) demonstrated the feasibility of the approach to influence behaviour(Jazayeri et al., 2012; Ju et al., 2018). Our work will extend this by measuring both the local layer-specific, as well as remote areal brain activation patterns associated with optogenetic stimulation of V1 and to what extent these activation patterns are associated with a visual percept.