Corticogeniculate feedback sharpens the temporal precision and spatial resolution of visual signals in the ferret
Proceedings of the National Academy of Sciences of the United States of America
The corticogeniculate (CG) pathway connects the visual cortex with the visual thalamus (LGN) in the feedback direction and enables the cortex to directly influence its own input. Despite numerous investigations, the role of this feedback circuit in visual perception remained elusive. To probe the function of CG feedback in a causal manner, we selectively and reversibly manipulated the activity of CG neurons in anesthetized ferrets in vivo using a combined viral-infection and optogenetics
... h to drive expression of channelrhodopsin2 (ChR2) in CG neurons. We observed significant increases in temporal precision and spatial resolution of LGN neuronal responses to drifting grating and white noise stimuli when CG neurons expressing ChR2 were light activated. Enhancing CG feedback reduced visually evoked response latencies, increased spike-timing precision, and reduced classical receptive field size. Increased precision among LGN neurons led to increased spike-timing precision among granular layer V1 neurons as well. Together, our findings suggest that the function of CG feedback is to control the timing and precision of thalamic responses to incoming visual signals. T he feedforward progression of sensory information from peripheral receptors through nuclei in the sensory thalamus to the primary sensory cortex is well understood. For example, much is known about how neurons in the primary sensory cortex represent elementary sensory features based on the inputs they receive from peripheral and thalamic neurons with well-defined receptive field properties. In addition to these feedforward circuits, mammalian sensory systems include a substantial feedback projection from the primary sensory cortex to the sensory thalamus (1). Despite a rich history of investigation, the functional role of corticothalamic feedback circuits in sensory perception remains a fundamental mystery in neuroscience. Our goal was to determine the functional contribution of corticothalamic feedback to vision. Corticogeniculate (CG) circuits link the primary visual cortex (V1) with the lateral geniculate nucleus of the thalamus (LGN) and constitute the first cortical feedback connection in the visual processing hierarchy (2). CG axons target LGN relay neurons, local interneurons within the LGN, and neurons in the visual portion of the thalamic reticular nucleus (TRN) that inhibit LGN relay neurons (3-5) (Fig. 1A) . Based on this pattern of axonal innervation, CG modulation of LGN neurons could include both monosynaptic excitation and disynaptic inhibition of LGN relay neurons via TRN and/or local LGN inhibitory circuitry. The CG circuit is anatomically robust-cortical synapses onto LGN relay neurons far outnumber retinal synapses (4); however, the receptive fields of LGN relay neurons reflect their retinal and not their cortical inputs (6). In part due to its subtle influence on LGN responses, the function of CG feedback has remained elusive. There have been numerous experimental examinations of CG function-using methods with varying degrees of selectivity and/or reversibility of CG manipulation-and a corresponding variety of proposed functional roles for feedback. Some have proposed that CG feedback modulates the gain (7-14) and/or the spatiotemporal properties of LGN neurons (15-17). Others have proposed that corticothalamic feedback controls whether thalamic neurons are in a state of net excitation or inhibition (8, 12), depending upon oscillatory activity in corticothalamic networks (18). Our goal was to conduct a causal and comprehensive examination of CG function using a combination of virus-mediated gene delivery and optogenetic strategies to selectively and reversibly manipulate the activity of CG neurons in vivo. We examined CG function in the ferret, a visual carnivore and useful model of visual system development and function (19) . We systematically measured visual responses of ferret LGN neurons to a variety of stimuli while CG feedback was optogenetically enhanced. We discovered that enhancing CG feedback significantly reduced visual response latencies, increased spike-timing precision, and increased spatial resolution among LGN neurons. Enhancing CG feedback did not alter contrast sensitivity or spatial/temporal frequency tuning preferences of LGN neurons, although LGN neuronal responses to gratings varying in temporal frequency were slightly enhanced. Our findings suggest that the overall function of corticothalamic feedback in sensory perception is to control the temporal precision and spatial resolution of thalamic responses to incoming sensory inputs to boost the efficacy of feedforward signal transmission to the cortex. Results Using optogenetics, a technology that enables selective and reversible manipulation of neuronal activity in the intact brain (20), we performed a causal experiment to determine the influence of CG feedback on LGN neurons. To selectively and reversibly manipulate Significance The functional role of corticothalamic circuits, connecting the cortex to the thalamus in the feedback direction, has remained a fundamental mystery in neuroscience. In spite of the fact that corticothalamic inputs are numerous, their influence on thalamic activity is modest. We used an innovative combination of virus-mediated gene delivery and optogenetics to probe the function of corticothalamic feedback in vision. We found that corticothalamic feedback does not alter the visual response properties of thalamic neurons, but instead controls the timing and fidelity of their responses to incoming visual inputs. Thus, our results provide an answer to a long-standing question in neuroscience: A key function of corticothalamic feedback is to control the timing and precision of thalamic responses.