Disassembly and Rewiring of a Mature Converging Excitatory Circuit Following Injury

Abstract

Specificity and timing of synapse disassembly in the CNS are essential to learning how individual circuits react to neurodegeneration of the postsynaptic neuron. In sensory systems such as the mammalian retina, synaptic connections of second-order neurons are known to remodel and reconnect in the face of sensory cell loss. Here we analyzed whether degenerating third-order neurons can remodel their local presynaptic connectivity. We injured adult retinal ganglion cells by transiently elevating intraocular pressure. We show that loss of presynaptic structures occurs before postsynaptic density proteins and accounts for impaired transmission from presynaptic neurons, despite no evidence of presynaptic cell loss, axon terminal shrinkage, or reduced functional input. Loss of synapses is biased among converging presynaptic neuron types, with preferential loss of the major excitatory cone-driven partner and increased connectivity with rod-driven presynaptic partners, demonstrating that this adult neural circuit is capable of structural plasticity while undergoing neurodegeneration.

Alpha retinal ganglion cells in pigmented mice retina: number and distribution

“…In addition, other authors have characterized the presence of calbindin expressed in ONs-αRGCs (in addition to the labeling of a subpopulation of amacrine cells; Krieger et al, 2017;Sonoda et al, 2020) which, when colocalized with an αRGC pan-marker, allows for reliable detection of ONs-αRGCs. Previous studies have documented that these M4-ipRGCs (ONs-αRGCs) are 10.3389/fnana.2022.1054849 more resistant to retinal injury (El-Danaf and Huberman, 2015;Ou et al, 2016;Tran et al, 2019), due to their ability to alter their synaptic connectivity pattern after injury to promote survival (Della Santina et al, 2021). However, there is not a complete consensus on this characteristic, as in other studies, M4-ipRGCs have not been more resistant than the rest of the RGCs (Gallego-Ortega et al, 2021;Gao et al, 2022), reviewed in Tran et al (2019).…”

Tunable degrees of neurodegeneration in rats based on microsphere-induced models of chronic glaucoma

“…In loop-induced 46,47 and microspheres-induced ocular hypertensive models 48 , an increase in ERG signal has been described as a reflection of synaptic imbalance at the onset of intraocular pressure increase. And a recent study demonstrated a structural plasticity with increased synaptic connectivity with rods while undergoing glaucoma degeneration 49 . This hyperactivity may be one of the earliest dysfunctions of the pathophysiological process of neurodegeneration 50 (suggested in other neurodegenerative diseases such as Alzheimer's disease 51 or multiple sclerosis 52 ).…”