Neurons in the dorsolateral geniculate nucleus (dLGN) of the thalamus receive a substantial proportion of modulatory inputs from corticothalamic (CT) feedback and brain stem nuclei. Hypothesizing that these modulatory influences might be differentially engaged depending on the visual stimulus and behavioral state, we performed in vivo extracellular recordings from mouse dLGN while optogenetically suppressing CT feedback and monitoring behavioral state by locomotion and pupil dilation. For naturalistic movie clips, we found CT feedback to consistently increase dLGN response gain and promote tonic firing. In contrast, for gratings, CT feedback effects on firing rates were mixed. For both stimulus types, the neural signatures of CT feedback closely resembled those of behavioral state, yet effects of behavioral state on responses to movies persisted even when CT feedback was suppressed. We conclude that CT feedback modulates visual information on its way to cortex in a stimulus-dependent manner, but largely independently of behavioral state.

8Neurons in the dorsolateral geniculate nucleus (dLGN) of the thalamus are contacted by a large number of feedback synapses from cortex, whose role in visual processing is poorly understood. Past studies investigating this role have mostly used simple visual stimuli and anesthetized animals, but corticothalamic (CT) feedback might be particularly relevant during processing of complex visual stimuli, and its effects might depend on behavioral state. Here, we find that CT feedback robustly modulates responses to naturalistic movie clips by increasing response gain and promoting tonic firing mode. Compared to these robust effects for naturalistic movies, CT feedback effects were less consistent for simple grating stimuli. Finally, while CT feedback and locomotion affected dLGN responses in similar ways, we found their effects to be largely independent. We propose that CT feedback and behavioral state use separate routes to powerfully modulate visual information on its way to cortex.

Default network regions appear to integrate information over time windows of 30 seconds or more during narrative listening. Does this long-timescale capability require the hippocampus? Amnesic behavior suggests that the hippocampus may not be needed for online processing when input is continuous and semantically rich: amnesics can participate in conversations and tell stories spanning minutes, and when tested immediately on recently heard prose their performance is relatively preserved. We hypothesized that default network regions can integrate the semantically coherent information of a narrative across long time windows, even in the absence of the hippocampus. To test this prediction, we measured BOLD activity in the brain of a hippocampal amnesic patient (D. A.) and healthy control participants while they listened to a seven-minute narrative. The narrative was played either in its intact form, or as a paragraphscrambled version, which has been previously shown to interfere with the long-range temporal dependencies in default network activity. In the intact story condition, D. A.'s moment-by-moment BOLD activity spatial patterns were similar to those of controls in low-level auditory cortex as well as in some high-level default network regions (including lateral and medial posterior parietal cortex). Moreover, as in controls, D. A.'s response patterns in medial and lateral posterior parietal cortex were disrupted when paragraphs of the story were presented in a shuffled order, suggesting that activity in these areas did depend on information from 30 seconds or more in the past. Together, these results suggest that some default network cortical areas can integrate information across long timescales, even in the absence of the hippocampus.People with hippocampal damage are profoundly impaired in recalling information after a distraction (Milner, 1966), or "as soon as their attention shifts to a new topic" (Milner, 2005). At the same time, these amnesic individuals are able to engage in conversation, retain near-normal immediate recall for prose passages (Baddeley and Wilson, 2002), and tell globally coherent stories (Keven et al., 2018;Kurczek and Duff, 2011;Rosenbaum et al., 2009). How is this possible? One potential explanation is that, in the absence of major topic changes or surprises that create a distraction, amnesic individuals are able to rely on default network cortical regions for retention of semantically-rich information across time. Default network areas are proposed to carry slowly-changing information during continuous natural input such as stories and conversation (Hasson et al., 2015). In healthy people, these areas are functionally coupled to the hippocampus and may work together to accumulate, maintain, and integrate information across events. However, it is an open question whether the long-timescale capability of default network regions depends critically on interactions with the hippocampus .In this study, we investigated whether default network areas can integrate information over tens of se...

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Pupil size is a commonly used proxy for waking brain states such as arousal, and has been related to activity modulations in cortical sensory areas. Here, we asked whether the dorsolateral geniculate nucleus (dLGN), which provides sensory input to the visual cortex, is modulated by pupil-indexed arousal. Observing that the pupil size oscillates at multiple timescales, we developed a method to show that the spiking mode of the dLGN is predicted by pupil size oscillations over several of these timescales. Overall, we found that tonic spikes preferentially occurred during pupil dilation, while bursts occurred during contraction. These preferences could not be explained solely by pupil size per se or by the locomotion of the animal, and were also present during periods of stimulus viewing. We conclude that dLGN spiking activity is modulated by pupil-indexed arousal processes on various timescales, influencing the mode in which sensory signals are passed on to the cortex.