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Published on: November 2, 2020
Axonal regrowth of layer II-III visual-projecting cortical neurons in rats fails beyond eye opening
Linda Domballe1, Frédéric Gaillard, Afsaneh Gaillard
1Neurophysiology Group, LBSC, UMR 6558, CNRS, Faculty of Sciences, 40 avenue du Recteur Pineau, F-86022 Poitiers, France.
Insights
Fetal occipital neurons grafted into rat visual cortex receive inputs from various brain regions, decreasing with recipient age. Adult grafts primarily receive input from layer VI neurons, indicating a critical developmental window for connectivity.
Area of Science:
- Neuroscience
- Developmental Neurobiology
- Cortical Plasticity
Background:
- Fetal neurons grafted into the developing brain can integrate and respond to stimuli.
- Understanding the developmental timing of neural circuit formation is crucial for regenerative medicine.
- The visual cortex is a well-studied area for neural plasticity and connectivity studies.
Purpose of the Study:
- To investigate the impact of recipient age on the formation of host-graft connections in the visual cortex.
- To characterize the laminar origin of inputs to grafted fetal neurons.
- To determine the developmental timeline for establishing adult-like connectivity patterns.
Main Methods:
- Fetal occipital neurons (E16) were grafted into the visual cortex of albino rats at various postnatal ages (P0-P120).
- Photic stimulation was used to assess graft activation and functional integration.
- Tracing techniques were implicitly used to identify input origins from ipsilateral brain regions.
Main Results:
- Grafted neurons were activated by light, receiving inputs from the claustrum, periallocortex, isocortex, thalamus, and subthalamic/hypothalamic nuclei.
- The number of inputs decreased significantly with increasing recipient age at grafting.
- Isocortical input shifted from equal contribution by superficial (II-III) and deep (V-VI) layers in neonates to predominantly layer VI input in adults.
- Layer VI neurons maintained the capacity to innervate grafts even in adult recipients, unlike superficial layers.
Conclusions:
- The age of the recipient critically influences the pattern and extent of host-graft connectivity.
- A specific developmental window, closing around postnatal day 15 (eye opening), exists for supragranular neuron innervation.
- Infragranular neurons, potentially representing earlier born cells, retain synaptic plasticity capacity into adulthood.
Abstract:
Fetal neurons (embryonic age E16) of occipital origin grafted in the visual cortex of albino rats at increasing postnatal stages (P0, P7, P15, P30, P60, P120) can be activated by photic stimulation. Inputs originate from five major areas of the brain ipsilateral to the graft, namely, the claustrum, the periallocortex/proisocortex, the isocortex, the visual thalamus, and some unspecific subthalamic and hypothalamic nuclei. All inputs decrease in number with the age at which grafting was performed. Isocortical afferents exhibit furthermore a progressive laminar shaping. In neonates, layer II-III and layer V-VI neurons contribute equally to the graft input. In adults, grafts receive prominent input (approximately 70-80%) from layer VI neurons whereas layer II-III neurons account for less than 10%. Proportions of layer IV (approximately 2-4%) and layer V (approximately 15-20%) neurons innervating the graft remain stable, irrespective of the age of the recipient. The adult pattern of connectivity between the host brain and the graft establishes in frontal and temporal areas 1 week earlier than in occipital areas. It is nearly completed in postnatal day 15 (P15) grafted recipients. Supragranular neurons would be thus unable to innervate and to make stable synapses at the graft level beyond P15, i.e., when eyes open. Some infragranular neurons (supposedly remnants of the earliest generated cortical cell population) still have this capacity in adults.
