Premature vision drives aberrant development of response properties in primary visual cortex

Reviewer #1 (Public review):

The authors note that very premature infants experience the visual world early and, as a consequence, sustain lasting deficits including compromised motion processing. Here they investigate the effects of early eye opening in ferret, choosing a time point after birth when both retinal waves and light traveling through closed lids drive sensory responses. The laboratory has long experience in quantitative studies of visual response properties across development and this study reflects their expertise.

The investigators find little or no difference in mean orientation and direction selectivity, or in spatial frequency tuning, as a result of early eye opening but marked differences in temporal frequency tuning. These changes are especially interesting as they relate to deficits seen in prematurely delivered children. Temporal frequency bandwidth for responses evoked from early-opened contralateral eyes were broader than for controls; this is the case for animals in which either one or both eyes were opened prematurely. Further, when only one eye was opened early, responses to low temporal frequencies were relatively stronger.

The investigators also found changes in firing rate and signs of response to visual stimuli. Premature eye-opening increased spontaneous rates in all test configurations. When only one eye was opened early, firing rates recorded from the ipsilateral cortex were strongly suppressed, with more modest effects in other test cases.

As the authors' discussion notes, these observations are just a starting point for studies underlying mechanism. The experiments are so difficult to perform and so carefully described that the results will be foundational for future studies of how premature birth influences cortical development.

Reviewer #2 (Public review):

In this paper, Griswold and Van Hooser investigate what happens if animals are exposed to patterned visual experience too early, before its natural onset. To this end, they make use of the benefits of the ferret as a well-established animal model for visual development. Ferrets naturally open their eyes around postnatal day 30; here, Griswold and Van Hooser opened either one or both eyes prematurely. Subsequent recordings in the mature primary visual cortex show that while some tuning properties like orientation and direction selectivity developed normally, the premature visual exposure triggered changes in temporal frequency tuning and overall firing rates. These changes were widespread, in that they occurred even for neurons responding to the eye that was not opened prematurely. These results demonstrate that the nature of the visual input well before eye opening can have profound consequences on the developing visual system.

The conclusions of this paper are well supported by the data, but some aspects of the data could be clarified, and the discussion could be extended.

(1) The assessment of the tuning properties is based on fits to the data. Presumably, neurons for which the fits were poor were excluded? It would be useful to know what the criteria were, how many neurons were excluded, and whether there was a significant difference between the groups in the numbers of neurons excluded (which could further point to differences between the groups).

(2) For the temporal frequency data, low- and high-frequency cut-offs are defined, but then only used for the computation of the bandwidth. Given that the responses to low temporal frequencies change profoundly with premature eye opening, it would be useful to directly compare the low- and high-frequency cut-offs between groups, in addition to the index that is currently used.

(3) In addition to the tuning functions and firing rates that have been analyzed so far, are there any differences in the temporal profiles of neural responses between the groups (sustained versus transient responses, rates of adaptation, latency)? If the temporal dynamics of the responses are altered significantly, that could be part of an explanation for the altered temporal tuning.

(4) It would be beneficial for the general interpretation of the results to extend the discussion. First, it would be useful to provide a more detailed discussion of what type of visual information might make it through the closed eyelids (the natural state), in contrast to the structured information available through open eyes. Second, it would be useful to highlight more clearly that these data were collected in peripheral V1 by discussing what might be expected in binocular, more central V1 regions. Third, it would be interesting to discuss the observed changes in firing rates in the context of the development of inhibitory neurons in V1 (which still undergo significant changes through the time period of premature visual experience chosen here).