The development of feature selectivity across the visual system

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Background: The mammalian visual system is organized in a hierarchical manner, with the complexity of neuronal responses increasing as you move from the retina to higher brain regions. This increase in complexity can be measured via the feature selective responses of neurons in different brain areas, such as center-surround responses in the retina, orientation and direction selective responses in visual cortex, and visual object selective responses in temporal cortex. However, little is known about how complex feature selectivity arises, both within and across brain regions. To gain a better understanding of how feature selectivity is generated, neuronal circuits can be studied at the level of single-cell functional connectivity, by directly comparing the feature selectivity of a single postsynaptic neuron to the feature selectivity of its presynaptic inputs.******Objective 1: Compare the feature selectivity of individual layer 4 starter' neurons in primary visual cortex to the feature selectivity of their presynaptic inputs in visual cortex. To do this, we will perform single-cell initiated transsynaptic circuit tracing from layer 4 of visual cortex with modified rabies viruses. We will present mice with visual stimuli and measure the light responses in the synaptically connected neurons using in vivo 2-photon calcium imaging. ******Objective 2: Compare the feature selectivity of individual layer 4 starter neurons to their presynaptic neurons in the lateral geniculate nucleus (LGN) of the thalamus. Using the same experimental paradigm as outlined in Objective 1, we will monitor the neuronal activity of individual cortical layer 4 starter cells and their presynaptic LGN inputs using in vivo 2-photon calcium imaging.******Objective 3: Compare the feature selectivity of the retinal ganglion cells that provide di-synaptic input to individual neurons in layer 4 of visual cortex. We will implement a novel, serial circuit tracing strategy, involving the use of single-cell-initiated rabies virus tracing from individual cells in multiple brain regions, to drive rabies to jump from a single LGN neuron that is presynaptic to the layer 4 cortical starter neuron to presynaptic retinal ganglion cells. We will then perform 2-photon calcium imaging from retinal ganglion cells in vitro during visual stimulation to examine the feature selectivity of these neurons.******Outcomes: These experiments will provide strong direct evidence regarding how distinct feature selective responses, in particular orientation and direction selective responses, arise in the early visual system. This will be the first project to directly monitor how a single feature selectivity arises across multiple brain regions by focusing on synaptically connected neurons in three distinct brain regions. In the future, similar approaches could be used to understand more complex feature selective responses, such as visual object selectivity.