Research ArticleStructural and Functional Plasticity in the Dorsolateral Geniculate Nucleus of Mice following Bilateral Enucleation
Introduction
The activity of neuronal networks in the brain is one of the most stable components of the nervous system and this stability is required throughout life to maintain functional connectivity for effective information transfer (Turrigiano, 1999, Turrigiano, 2008, Turrigiano and Nelson, 2004, D’Angelo, 2010). This results from the nervous system’s ability to monitor changes in network activity and compensate via modulation of neuronal structure, intrinsic excitability, and/or synaptic function (Abbott and Nelson, 2000, Darlington et al., 2002, Schulz, 2006, Beck and Yaari, 2008, Howland and Wang, 2008, Gainey et al., 2009, Turrigiano, 2012, Lambo and Turrigiano, 2013, Bliss et al., 2014, Hauser et al., 2014, Fernandes and Carvalho, 2016, Chowdhury and Hell, 2018, Meriney and Fanselow, 2019). Such plasticity in cortical and sub-cortical structures has been reported during maturation as well as in adulthood in response to learning and memory or injury and is an important feature of the nervous system during learning and development as well as in disease.
One of the key structures of the visual system is the dorsolateral geniculate nucleus (dLGN), which receives direct projections from retinal ganglion cells, integrates visual responses (Mazade and Alonso, 2017, Monavarfeshani et al., 2017), and relays that information to the primary visual cortex (Sherman and Guillery, 2002, Chen et al., 2016). Disruption in the flow of information resulting from injury or disease will interrupt normal communication and may trigger compensatory mechanisms to counter the disruption. The developmental plasticity of the dLGN is well-established and involves pruning and strengthening of synaptic inputs from retinal ganglion cells, refinement of dLGN relay neuron dendritic branching, and maturation of intrinsic excitability (Chen and Regehr, 2000, Hooks and Chen, 2006, Hooks and Chen, 2008, Bickford et al., 2010, Hong and Chen, 2011, Krahe et al., 2012, El-Danaf et al., 2015, Thompson et al., 2016, Litvina and Chen, 2017a, Guido, 2018). A handful of studies have also documented plasticity in the dLGN in adult mice, including in monocular deprivation (Jaepel et al., 2017, Rose and Bonhoeffer, 2018), monocular enucleation (Gonzalez et al., 2005), a mouse model of inflammatory demyelination (Araújo et al., 2017), and ocular hypertension (Bhandari et al., 2019, Van Hook et al., 2021). These studies have shown that alterations in visual function or optic nerve health lead to changes in inputs to the dLGN from retina and the cortex as well as changes in the structure and function of dLGN relay neurons (Yücel et al., 2001, Hayakawa and Kawasaki, 2010, Krahe and Guido, 2011, Ly et al., 2011, Krahe et al., 2012, You et al., 2012, El-Danaf et al., 2015, Pang et al., 2015, Araújo et al., 2017, Bhandari et al., 2019).
Given that plasticity in the dLGN has been well established during development as well as adulthood, it is still unknown how the mature dLGN responds to severe optic nerve injury. While we have previously explored the influence of ocular hypertension (Bhandari et al., 2019, Van Hook et al., 2021), which induces a low-level and chronic optic nerve injury and alteration in RGC output, our goal here was to use a more dramatic insult to probe plasticity processes in the dLGN. To accomplish this, we bilaterally enucleated adult mice to test the hypothesis that traumatic optic nerve injury will induce functional changes in the neurons and synapses in the dLGN.
Section snippets
Animals
All procedures were approved by the Institutional Animal Care and Use Committee at the University of Nebraska Medical Center. C57 Bl/6J mice (Jackson Labs #000664) were used for excitability experiments. For optogenetic experiments, Chx10-cre;Ai32 (Litvina and Chen, 2017b) mice were used, generated by crossing Chx10-cre (Rowan and Cepko, 2004) (Chx10 BAC Jackson labs #005105) mice with Ai32 (Madisen et al., 2012) reporter line (Jackson labs #024109). Chx10-cre mice were a gift from Dr. Chinfei
Results
To evaluate the effects of traumatic optic nerve injury in the mature dLGN, we bilaterally enucleated adult mice and probed for changes in physiology and structure of the ganglion cell axon terminals as well as TC neurons. Our goal was to determine the time-dependent effects of severe injury at the retinogeniculate synapse, the rate and the extent of synaptic dysfunction, and responses of postsynaptic TC neurons to a relatively sudden and drastic loss of synaptic partners. Our findings
Discussion
Neuronal activity is one of the most stable components of the nervous system and stability is required throughout life to maintain functional connectivity and activity. The balance in neuronal activity is the result of closely monitored processes that regulate network activity and adapt via compensatory mechanisms including change in synaptic properties, intrinsic excitability, and/or neuronal structure. Plasticity of synaptic transmission and in neuronal excitability in the visual cortex in
Acknowledgements
We would like to thank Elizabeth Bierlein for comments on the manuscript. We are grateful to Dr. Chinfei Chen (Harvard Medical School) for supplying Chx10-Cre mice.
Author contributions
AB and MVH designed the experiments; AB, JS, TW, and MVH performed the experiments; AB, JS, TW, and MVH analyzed the data; AB and MVH wrote the manuscript and prepared figures; MVH acquired funding.
Declaration of interest
None.
Funding
This work was supported by National Institutes of Health (NIH/NEI R01 EY030507), BrightFocus Foundation National Glaucoma Research Program (G2017027), University of Nebraska Collaboration Initiative Seed Grant, and Molecular Biology of Neurosensory Systems COBRE grant (NIH/NIGMS, P30 GM110768).
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