Implications of light-mediated  Finally, I propose that the latest and most 

cellular refinement on  sophisticated imaging be used and a 

mammalian nervous system 
standardized rearing paradigm be 
development 
  employed in order to reduce confounding 
Kayla Maanum​1 
  variables in future studies. 
1​
Department of Integrative Biology,   
University of California, Berkeley, 
Berkeley, CA USA  Introduction 
 
Abstract  The effect of light on the human 

Light has been shown to alter the  body and its development has been of 

human body in important ways. Most well  interest to scientists for generations. With 

studied is light’s effects on human  artificial lighting from mobile devices and 

hormone levels, such as dopamine.  laptops pervading society, it is more 

However, recent scholarship has shown  important than ever to understand the 

that light actually influences in the  impact that man’s creation has on its 

developing nervous system - both in its  creator. 

function and its form. In this review, I  Studies on the impact of light have 

survey literature on the effect of light on  traditionally highlighted its effects on the 

the developing nervous system. I argue  neuroendocrine system. For example, a 

that light can play an instructive role at  subset of retinal neurons that encode light 

various locations within the nervous  directly project to the suprachiasmatic 

system, but plays a largely refinatory role.  nucleus of the hypothalamus, the body’s 

1
“master clock” which regulates melatonin 
 
secretion (Duffy and Czeisler, 2010). 

Melatonin levels rise when ambient 

lighting dims, causing sleepiness in 

humans. In consequence, blue light from 

electronic tablets, phones and laptops has 

 
been shown to suppress blood melatonin 
Figure 1. ​Schematic of neuronal pathways 
levels (Tosini, Ferguson and Tsubota, 
from the retina to primary visual cortex in 
2016). Therefore, light has a large impact 
humans; light (yellow arrows) entering the 
on human ​hormonal​ physiology. 
eyes. (Adapted from Elster, 2019.) 
Research from past half century 
 
has only just begun to scratch the surface 
stimulation for firing via increased 
of light-mediated changes in neuronal 
neurotransmitter receptor production at 
morphology. It has been shown that light 
the subcellular level.​ ​Furthermore, the 
stimulation and different levels of ambient 
growth and retraction of dendritic spines 
light greatly affect functionality of neurons 
within the neurons are shown in response 
in different regions of the brain via 
to many types of sensory experiences, not 
subcellular protein changes (reviewed in 
just visual experience (Holtmaat and 
Holtmaat and Svoboda, 2009)). Mainly, 
Svoboda, 2009). However, much less is 
visual deprivation in mice induces 
understood about the impact of light at 
long-term depression of neurons, whereby 
the cellular level in the nervous system.  
neurons require a lower threshold of  

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 Because the null hypothesis  neuronal structure due to light deprivation 

assumes that normal nervous system  may have implications about the role of 

morphological development occurs  light and visual experience on nervous 

independently of environmental light levels  system functionality. 

and is dependent on genetically-encoded   

factors, available research seems to be  Role for light in visual system 

biased toward results that reject this null  development 

hypothesis. Available literature suggests  Retina 

that light has a range of effects on cells in  The retina is a cup of neural tissue 

various regions of the central nervous  in the posterior segment of the eye which 

system (CNS), including the visual circuit,  contains the neurons responsible for 

hippocampus and cerebellum.  initiating visual stimulus processing. These 

The aim of this review is to assess  neurons, called retinal ganglion cells 

to what extent neuronal regions are  (RGCs), are mostly morphologically 

dependent on light for normal system  stagnant in postnatal development, 

development and uncover questions that  according to studies in mice (Chalupa and 

may be answered in the future. In light of  Gunhan, 2004). In contrast, recent 

the evolutionary model of “form follows  scholarship from Elias et al. shows that in 

function”-- in which vertebrate  a subset of direction-selective RGCs, 

morphology at all levels of the organism  J-RGCs, light deprivation prevented the 

have evolved specialized shape that  decrease in dendritic field size that occurs 

complements function, alterations in  in normally reared mice (Elias et al., 2018; 

3
Figure 2). In addition, dark rearing  plexiform layer (IPL). The authors therefore 

prevented expanded dendritic lamination  show that in some retinal neurons, light 

within different layers of the inner   and visual experience serve to refine, 

  rather than reconstruct, cellular 

morphology.  

Functional studies of neurons in the 

retina shows that light does not play a role 

in neuronal development. Anishchenko 

and colleagues found that even before full 

maturation of the physical retinal circuit in 

rats, the immature RGC receptive fields 

had already fully developed compared to 

mature adult RGC receptive fields 

Figure 2.​ ​Visual deprivation alters dendritic 
(Anishchenko et al., 2010) A cell’s 
morphology in direction-selective J-RGCs 
receptive field is region of space that 
(reproduced from Elias et al., 2018). ​(​A1-2​) 
when stimulated with light will produce 
Representative images of individual control 
firing in a particular neuron. This study 
and dark-reared J-RGCs from adult mice. 
indicates that functional activity of these 
(​C​)​ Dendritic field area of adult dark-reared 
neurons develops independently of visual 
(black) J-RGCs are significantly larger than 
experience before eye opening. 
control (blue). (​ ​F​)​ Intensity level of 
However, one key assumption that 
fluorescent-labelled J-RGCs shows wider 
these authors made that has recently been 
level of laminar projection in control mice. 

4
disproven is that before rodents open their  complete darkness). Here, circuit-wide 

eyes postnatally, they receive little visual  functionality is altered by light deprivation.  

input through eyelids or that the retinal  Due to these conflicting results about 

circuits are not yet mature enough to  neurons in the retina, it is important that 

influence function of downstream neuronal  the field move forward using similar 

targets. However, a later study from the  methods for visual deprivation and the 

same group showed that the  number of assumptions made. 

direction-selective functionality at the  Retinogeniculate synapse 

system level is altered when mice are  Since neurons connect to each 

deprived of light stimuli prior to eye  other in circuit, downstream neurons 

opening (Bos, Gainer and Feller, 2016).  within the visual circuit may be affected by 

Thus, even prior to retinal circuit  retinal neuron changes. RGC axons 

maturation, the neural circuit is influenced  bundle together and project to various 

by visual experience.  nuclei within the brain. These regions 

Bos and colleagues show that while  include the superior colliculus (SC) and 

direction selective property of individual  lateral geniculate nucleus (LGN) of the 

RGCs is strongly maintained,  hypothalamus (Figure 1). As the retinal 

population-wide analysis reveals the  projections innervate inside the brain, a 

circuit as a whole is less finely tuned to the  subset of axons segregate and cross over 

four cardinal directions of motion when  to the contralateral side of the brain. 

mice are deprived of visual experience via  Light that passes through young 

a dark-rearing method (mice are housed in  mouse eyelids before eye opening plays 

5
an instructive role in directing the  neurons was calculated rather than 

segregation of retinal axons to the  quantified  

dorsolateral geniculate nuclei (dLGN) of 

the two thalami (Tiriac, Smith and Feller, 

2018). The authors use 3D reconstructions 

of the entire neuronal circuit to show that 

segregation of the projections to the 

 
dLGN, but not other projection targets, is 
Figure 3. ​Light deprivation slightly reduces 
slightly reduced when the mice are 
eye-specific segregation even before eye 
deprived of visual experience. 
opening (reproduced from Tiriac, Smith 
Interestingly, cellular refinement at the 
and Feller, 2018). Shaded gray region 
retinogeniculate synapse can likewise 
shows higher degree of overlap in 
occur later in postnatal development. Late 
contralateral and ipsilateral axonal 
visual deprivation of mice at postnatal day 
projection cross-sections within 
20 disrupts the retinogeniculate synapse  
dark-reared dLGN.  
by weakening existing connections 
 
between axonal projections from the retina 
directly, these results are novel in that they 
and the lateral geniculate nucleus and 
show that visual experience plays a role in 
recruiting retinal input from additional 
maintaining​ a refined eye-to-brain neural 
afferent neurons (Hooks and Chen, 2006). 
circuit into adulthood. 
Although these number of afferent 
At the retinogeniculate synapse, 

light exposure during early and late 

6
postnatal development serves to refine  raised in dim light required longer time to 

afferent connections. It has yet to be  learn where a hidden platform was 

investigated whether early changes to the  located, implying these animals have 

synapse morphology via dark rearing can  impaired memory compared to bright-light 

later be reversed with light exposure. This  raised animals (Soler et al., 2017). 

is one avenue for future study.  However, this study also shows that 

  morphological changes shown above are 

Light induces reversible change in  not permanent, as follow up exposure to 

hippocampal neuron migration  bright light recovers deficits in learning 

and dendritic spine densities. 

Different intensities of light, not 

merely the presence or absence of it, can  Since behavioral assays are 

also have effects on deeper brain  commonly used to study memory and 

structures outside the visual system. Soler  models for human neuropsychiatric 

et al. found that in diurnal rats, numbers of  disorders, it makes sense that 

hippocampal CA1 cell bodies decreased  hippocampal studies include this 

significantly, and mushroom and stubby  experiment.  

dendritic spine density decreased in rats 

Role for light in the cerebellum 
housed in dimly-light conditions (Soler et 
A hindbrain structure of the central 
al., 2017). Other than these morphological 
nervous system that controls coordination 
results, the authors quantified behavioral 
and has no direct afferent from the visual 
results by testing spatial memory using a 
system is the cerebellum. Even so, the 
Morris Water Maze. They found that rats 
cerebellum shows differential cell 

7
migration rates as a result of light  Despite the affirmative role of light 

stimulation.  in shaping neuronal dynamics here, this 

study was performed ​in vitro. ​Though 

Li and colleagues (2012) show that 
useful, future ​in vivo s​ tudies would provide 
cerebellar levels of IGF-1 in mice are 
a more accurate results that would allow 
controlled by light exposure, and that the 
characterization of light’s role in this 
speed of cerebellar granule cell migration 
developmental process. 
is mediated by IGF-1 receptor activity. 

More specifically, they show that granule  Conclusions 

cell migration speed is dose-dependent on  Taken together, the reviewed 

added IGF-1 in vitro. The mechanism by  research reveals that while light 

which light modulates IGF-1 levels  deprivation can alter normal development 

remains unknown. The cerebellum  of various neuronal features in different 

receives no direct input from sensory  areas of the central nervous system, these 

neurons, but from higher order cerebral  changes are small in scale. The higher 

cortex and spinal cord. Since light does  order brain regions also tend to have 

not directly impact cerebellar neurons,  comparatively smaller changes. Because 

cellular signaling must control IGF-1 levels  of this relatively new observation, the field 

in the organ. Therefore, changes in light  has much more rigorous work to do in 

can be transmitted into deeper brain  order to corroborate or dispell previous 

structures like the cerebellum to induce  assumptions about neuron development in 

structural change.  the visual system and deeper regions in 

the brain. 

8
A case for dark-rearing animal models  exact age its retinal circuit becomes fully 

As stated earlier in the review, it is  developed and “mature.” Therefore, 

difficult to directly compare the results of  dark-rearing controls for this natural 

various studies because of the different  variation in development by allowing (or 

methods employed by each author. While  rather, disallowing) the same amount of 

it was traditionally acknowledged that  light to reach the immature and mature 

postnatal development of the retinal circuit  neuronal structures in different animals. 

in rodents is immature before eye opening,  More sophisticated imaging techniques 

new evidence suggests that immature  are required for high resolution analysis 

circuitry does not preclude anatomical  As technology advances and higher 

changes to occur.   resolution imaging is made available, it 

Dark-rearing, or housing animal  has become increasingly important to 

models in complete darkness, is an  study microscopic neuronal features with 

experimentally sound way for researchers  the most sophisticated softwares. As 

to control for any light influence at all.  evidenced by conflicting results 

Mice and rats open their eyes around two  presented earlier in this review, subtle 

weeks postnatally, but the exact age in  deviations in structure can be detected by 

which they do varies from pup to pup.  whole-brain imaging, which digitally 

Even if it were true that light stimuli does  re-constructs 3D sections of image slices 

not influence the immature retinal circuit  of the brain region of interest. This 

before eye opening, there is individual  technique is more accurate, so Tiriac et 

variation between pups around at what  al. claim, at revealing fine details of 

9
segregated neuron projections than using  In regions that are traditionally 

one representative slice of brain for  studied in the context of protein and 

analysis. Considering RGC axonal  molecular expression (i.e. hippocampus 

projections in humans are less than 1  and cerebellum) the underlying 

micron in diameter (FitzGibbon and Taylor,  mechanisms have already begun to be 

2012). Tiriac et al.’s claims may be valid.  investigated, as reviewed above.  

What are the underlying molecular  Does altered cellular form affect global 

mechanisms of light-mediated  behavior? 

alterations?  Perhaps all of this evidence begs 

Currently, mechanisms underlying  the final question: do these structural 

changes in retinal neurons (i.e. J-RGCs)  changes in CNS neurons actually matter? 

remain unknown, although the authors  What I mean by this is does the organism 

speculate it may be due to changes in  as a whole suffer ​behavioral 

NMDA receptors (Elias et al., 2018). ​ ​The  consequences of unrefined neuronal 

subcortical visual system discussed here  morphology as a result of light 

clearly shows evidence for the role of  deprivation?  

visual experience in physical circuit  For now, it is difficult to say for 

formation, yet changes in factors or  sure. There is some evidence that 

receptor counts have not yet been  abnormal behavioral phenotypes may be 

investigated. This provides a rich area for  induced as a result of anatomical changes 

future studies in roles for visual  as reviewed here. Yet, more behavioral 

experience.  assays need to be developed and tested 

10
that can quantify the effects of these  development of direction-selective 
circuits’. ​Curr Biol.,​ 26 (10), pp.1367-1375. 
anatomical changes in these particular   
Chalupa, L.M. and Gunhan, E., (2004). 
“hotspot” regions of interest, if any 
‘Development of On and Off retinal 
behavioral differences exist at all.   pathways and retinogeniculate 
projections’, ​Prog Retin Eye Res​, 23 (1), 
If this final question is affirmed,  pp. 31-51. 
 
then the results could have profound  Duffy, J. and Czeisler, C, (2010). ‘Effect of 
effects on the way humans view light from  light on human circadian physiology’, 
Sleep Med Clin,​ 4 (2), pp.165-177. 
the environment and from electronic   
Elias, E., Yang, N., Wang, P., and Tian, N,. 
devices alike.   (2018). ‘Glutamate activity regulates and 
dendritic development of J-RGCs’. ​Front. 
 
Cell. Neurosci,​ 12:249. 
Acknowledgements   
Elster, A.D., (2018). ‘fMRI of the Visual 
K.M. would like to thank Kim Freeman and  System’, Elster LLC, viewed 09 March 
2019,<​http://mriquestions.com/visual.htm​l
the College Writing 161 class for their  >. 
 
insightful advice in drafting the 
FitzGibbon, T. and Taylor, S.F., (2012). 
‘Mean retinal ganglion cell axon diameter 
manuscript. 
varies with location in the human retina’, 
Jpn J Ophthalmol​, 56 (6), pp.631-637. 
   

References  Holtmaat, A. and Svoboda, K., (2009). 

‘Experience-dependent structural synaptic 
Anishchenko, A., Greschner, M., Elstrott,  plasticity in the mammalian brain’, ​Nature 
J., Sher, A., Litke, A.M., Feller, M.B., and  Reviews Neuroscience,10​, pp. 647-658. 
Chichilnisky, E.J., (2010). ‘Receptive field   
mosaics of retinal ganglion cells are  ​
Hooks, B.M. and Chen, C., (2006). 
established without visual experience’. ​J  ‘Distinct roles for spontaneous and visual 
Neurophysiol, 103 (​ 4), pp.1856-1864.  activity in remodeling the retinogeniculate 
  synapse’. ​Neuron,​ 52 (2), pp.281-291. 
 
Bos, R., Gainer, C. and Feller, M.B., 
(2016). ‘Role for visual experience in the  Soler, J.E., Robison, A.J., Nunez, A.A., 
and Yan, L., (2017). ‘Light modulates 

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hippocampal function and spatial learning   
in a diurnal rodent species: A study using   
male nile grass rat (​Arvicanthis niloticus​)’.   
Hippocampus, ​28 (3), pp.189-200. 
 
 
Tiriac, A., Smith, B. and Feller M.B., 
(2018). ‘Light prior to eye opening 
promotes retinal waves and eye-specific 
segregation’. ​Neuron, 1 ​ 00 (5), 
pp.1056-1065. 
 
Tosini, G., Ferguson, I., and Tsubota, K., 
(2016). ‘Effects of blue light on the 
circadian system and eye physiology,’ 22, 
pp. 61-72. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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