BDNF signaling in correlation-dependent structural plasticity in the developing visual system

Abstract

During development, patterned neural activity in input neurons innervating their target, instructs topographic map refinement. Axons from adjacent neurons, firing with similar patterns of neural activity, converge onto target neurons and stabilize their synapses with these postsynaptic partners (Hebbian plasticity). On the other hand, non-correlated firing of inputs promotes synaptic weakening and exploratory axonal growth (Stentian plasticity). We used visual stimulation to control the visually-evoked correlation structure of neural activity in ectopic ipsilaterally projecting (ipsi) retinal ganglion cell axons with respect to their neighboring contralateral eye inputs in the optic tectum of albino Xenopus laevis tadpoles. Multiphoton imaging of the ipsi axons in the live tadpole, combined with manipulation of brain-derived neurotrophic factor (BDNF) signaling, revealed that presynaptic p75NTR and TrkB both promoted axonal branch addition during Stentian plasticity, whereas predominantly postsynaptic BDNF signaling mediated activity-dependent Hebbian suppression of axon branch addition. Additionally, we found that BDNF signaling is required for local suppression of branch loss induced by correlated firing.

Emergence of synaptic organization and computation in dendrites

“…Clustering refines over development ( ) and cannot form when spontaneous activity is absent ( ; ). Further, experiments blocking individual molecules and their receptors implicate a family of signaling molecules called neurotrophic factors in this process ( ; ; ). Computational modeling demonstrates that the interactions between these neurotrophic factors effectively implement a local plasticity rule that can generate clustering ( ), where poorly synchronized synapses weaken and well-synchronized synapses stabilize ( ; ).…”

Activity-dependent synapse clustering underlies eye-specific competition in the developing retinogeniculate system

“…RGC axon refinement is a dynamic process involving branch stabilization and elimination based upon the relative activity patterns among neighboring inputs (37, 40). Axonal remodeling is partially regulated by synaptic transmission (41) and the induction of non-cell-autonomous stabilization and punishment signals (38, 39, 42). Although the precise mechanisms of axonal stabilization and punishment are not fully understood, it is likely that non-cell-autonomous signals operate at a local scale through direct cell-cell interactions or diffusible paracrine factors.…”

Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in Glaucoma: A Review of Current State of the Art

“…The broad range of functions served by BDNF owe to the complexities of neurotrophin production, secretion, and receptor signaling in the nervous system. Once secreted, BDNF can be activated in two forms: prodomain of BDNF (cleaved precursor protein; pro-BDNF) and mature BDNF (mBDNF), which exert their functions primarily through p75NTR and sortilin signaling and TrkB and p75NTR/TrkB, respectively ( Kutsarova et al, 2021 ). Although mBDNF has a high affinity of binding to TrkB, it binds to p75NTR when the expression level is aberrant, hence stimulating signaling cascades in the manner opposite to the TrkB receptor.…”

“…What is also known about BDNF is that compared to other NTFs, the former is the superior factor for the RGC survival under glaucomatous conditions ( Almasieh and Levin, 2017 ). This has been proven by the exogenous application of BDNF in the developing retinotectal system where the RGC axons showed arborization and growth, contrariwise to the depleted endogenous BDNF, which hampered presynaptic trafficking and axonal branch stabilization ( Kutsarova et al, 2021 ).…”