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Homeostatic structural plasticity can account for topology changes following deafferentation and focal stroke.

Butz M, Steenbuck ID, van Ooyen A - Front Neuroanat (2014)

Bottom Line: Homeostatic structural plasticity postulates that neurons aim to maintain a desired level of electrical activity by deleting synapses when neuronal activity is too high and by providing new synaptic contacts when activity is too low.Using our Model of Structural Plasticity, we explored how local changes in connectivity induced by a focal loss of input affected global network topology.Furthermore, deafferentated neurons increased their global but decreased their local efficiency and got longer tailed degree distributions, indicating the emergence of hub neurons.

View Article: PubMed Central - PubMed

Affiliation: Simulation Lab Neuroscience - Bernstein Facility for Simulation and Database Technology, Institute for Advanced Simulation, Jülich Aachen Research Alliance, Forschungszentrum Jülich Jülich, Germany.

ABSTRACT
After brain lesions caused by tumors or stroke, or after lasting loss of input (deafferentation), inter- and intra-regional brain networks respond with complex changes in topology. Not only areas directly affected by the lesion but also regions remote from the lesion may alter their connectivity-a phenomenon known as diaschisis. Changes in network topology after brain lesions can lead to cognitive decline and increasing functional disability. However, the principles governing changes in network topology are poorly understood. Here, we investigated whether homeostatic structural plasticity can account for changes in network topology after deafferentation and brain lesions. Homeostatic structural plasticity postulates that neurons aim to maintain a desired level of electrical activity by deleting synapses when neuronal activity is too high and by providing new synaptic contacts when activity is too low. Using our Model of Structural Plasticity, we explored how local changes in connectivity induced by a focal loss of input affected global network topology. In accordance with experimental and clinical data, we found that after partial deafferentation, the network as a whole became more random, although it maintained its small-world topology, while deafferentated neurons increased their betweenness centrality as they rewired and returned to the homeostatic range of activity. Furthermore, deafferentated neurons increased their global but decreased their local efficiency and got longer tailed degree distributions, indicating the emergence of hub neurons. Together, our results suggest that homeostatic structural plasticity may be an important driving force for lesion-induced network reorganization and that the increase in betweenness centrality of deafferentated areas may hold as a biomarker for brain repair.

No MeSH data available.


Related in: MedlinePlus

In the physiological case, compensatory network rewiring relies on the formation of new synapses from the intact zone to the LPZ. (A) Synapse numbers from the intact zone to the LPZ increase (green), while synapses numbers from the LPZ to the intact zone decrease (red). (B) All neurons in the intact zone (green) and most neurons in the LPZ (red) return to the homeostatic range following deafferentation. Neurons lose axonal and dendritic elements if their calcium concentration is lower than 0.1 or higher than 0.75 (dark gray background). Neurons form only dendritic elements if their calcium concentration is greater than 0.1 but lower than 0.4 (gray), and form both axonal and dendritic elements if their calcium concentration is greater 0.4 but lower than 0.65 (light gray). The homeostatic range, in which synaptic element numbers do not change, spans from 0.65 to 0.75. The diagram helps to match changes in topology with the current level of electrical activity. (C) The normalized average clustering coefficient γ of neurons in the LPZ (including connections with the entire network) decreases while neuronal activities are very low (<0.1) and increases as soon as activities of LPZ neurons are greater than 0.1. The first bump in clustering is brought about by ingrowing synapses from the intact zone into the LPZ, whereas the second rise in clustering is caused predominantly by new synapses within the LPZ, which are formed when calcium concentrations of LPZ neurons exceed 0.4. The γ of neurons in the intact zone (considering all their connections to any neuron in the entire network) decreases continuously after a temporary rise. (D) Average shortest paths from neurons in the intact zone to neurons in the LPZ show a steady decrease (green), while average path lengths from LPZ to intact zone neurons return to initial levels after a tri-phasic increase and decrease. (E) The clustering coefficient with no normalization (Equation 10) does not show a decrease for intact zone neurons as the normalized clustering coefficient γ does. (F) No differences were found between the characteristic path length and the normalized characteristic path length λ. Green curve indicates changes in clustering coefficient of intact zone neurons with the entire network. Means over five simulations per scenario. Shadings of the curves in (A,C–F) indicate standard deviations.
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Figure 4: In the physiological case, compensatory network rewiring relies on the formation of new synapses from the intact zone to the LPZ. (A) Synapse numbers from the intact zone to the LPZ increase (green), while synapses numbers from the LPZ to the intact zone decrease (red). (B) All neurons in the intact zone (green) and most neurons in the LPZ (red) return to the homeostatic range following deafferentation. Neurons lose axonal and dendritic elements if their calcium concentration is lower than 0.1 or higher than 0.75 (dark gray background). Neurons form only dendritic elements if their calcium concentration is greater than 0.1 but lower than 0.4 (gray), and form both axonal and dendritic elements if their calcium concentration is greater 0.4 but lower than 0.65 (light gray). The homeostatic range, in which synaptic element numbers do not change, spans from 0.65 to 0.75. The diagram helps to match changes in topology with the current level of electrical activity. (C) The normalized average clustering coefficient γ of neurons in the LPZ (including connections with the entire network) decreases while neuronal activities are very low (<0.1) and increases as soon as activities of LPZ neurons are greater than 0.1. The first bump in clustering is brought about by ingrowing synapses from the intact zone into the LPZ, whereas the second rise in clustering is caused predominantly by new synapses within the LPZ, which are formed when calcium concentrations of LPZ neurons exceed 0.4. The γ of neurons in the intact zone (considering all their connections to any neuron in the entire network) decreases continuously after a temporary rise. (D) Average shortest paths from neurons in the intact zone to neurons in the LPZ show a steady decrease (green), while average path lengths from LPZ to intact zone neurons return to initial levels after a tri-phasic increase and decrease. (E) The clustering coefficient with no normalization (Equation 10) does not show a decrease for intact zone neurons as the normalized clustering coefficient γ does. (F) No differences were found between the characteristic path length and the normalized characteristic path length λ. Green curve indicates changes in clustering coefficient of intact zone neurons with the entire network. Means over five simulations per scenario. Shadings of the curves in (A,C–F) indicate standard deviations.

Mentions: From our previous work on modeling cortical rewiring after focal retinal lesions (Butz and van Ooyen, 2013), we know that functional network repair can be brought about by an, also experimentally observed, ingrowth of connections from the intact zone to the LPZ (Darian-Smith and Gilbert, 1994; Yamahachi et al., 2009). For physiological network repair to go along with functional retinotopic remapping (as shown in mice Keck et al., 2008), we found that it is important that the majority of new connections impinging on deafferentated neurons originates from intact areas and transmits electrical activity from the intact zone to the LPZ. Here, we further investigate whether the changes in global topology parameters express this ingrowth of connections. For this, we first focus on the activity-dependent changes in synapse numbers and connectivity between the intact zone and the LPZ. The first 6 weeks are dominated by a loss of synapses originating from the LPZ (Figure 4A). This is a direct consequence of neuronal activities being low and calcium concentrations being below ηA = 0.4 (Figure 4B), which causes axonal elements to be removed. By contrast, axonal elements from the intact zone form additional synapses with the LPZ right from the onset of the lesion. Between 6 and 8 weeks after the lesion, most neurons in the LPZ have reached calcium levels of 0.4 and start forming additional axonal elements, connecting to targets in the LPZ as well as the intact zone. The number of recurrent synapses from the LPZ to the LPZ does thereby at no time exceeds the number of synapses from the intact zone to the LPZ, as required for a functional remapping to emerge.


Homeostatic structural plasticity can account for topology changes following deafferentation and focal stroke.

Butz M, Steenbuck ID, van Ooyen A - Front Neuroanat (2014)

In the physiological case, compensatory network rewiring relies on the formation of new synapses from the intact zone to the LPZ. (A) Synapse numbers from the intact zone to the LPZ increase (green), while synapses numbers from the LPZ to the intact zone decrease (red). (B) All neurons in the intact zone (green) and most neurons in the LPZ (red) return to the homeostatic range following deafferentation. Neurons lose axonal and dendritic elements if their calcium concentration is lower than 0.1 or higher than 0.75 (dark gray background). Neurons form only dendritic elements if their calcium concentration is greater than 0.1 but lower than 0.4 (gray), and form both axonal and dendritic elements if their calcium concentration is greater 0.4 but lower than 0.65 (light gray). The homeostatic range, in which synaptic element numbers do not change, spans from 0.65 to 0.75. The diagram helps to match changes in topology with the current level of electrical activity. (C) The normalized average clustering coefficient γ of neurons in the LPZ (including connections with the entire network) decreases while neuronal activities are very low (<0.1) and increases as soon as activities of LPZ neurons are greater than 0.1. The first bump in clustering is brought about by ingrowing synapses from the intact zone into the LPZ, whereas the second rise in clustering is caused predominantly by new synapses within the LPZ, which are formed when calcium concentrations of LPZ neurons exceed 0.4. The γ of neurons in the intact zone (considering all their connections to any neuron in the entire network) decreases continuously after a temporary rise. (D) Average shortest paths from neurons in the intact zone to neurons in the LPZ show a steady decrease (green), while average path lengths from LPZ to intact zone neurons return to initial levels after a tri-phasic increase and decrease. (E) The clustering coefficient with no normalization (Equation 10) does not show a decrease for intact zone neurons as the normalized clustering coefficient γ does. (F) No differences were found between the characteristic path length and the normalized characteristic path length λ. Green curve indicates changes in clustering coefficient of intact zone neurons with the entire network. Means over five simulations per scenario. Shadings of the curves in (A,C–F) indicate standard deviations.
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Figure 4: In the physiological case, compensatory network rewiring relies on the formation of new synapses from the intact zone to the LPZ. (A) Synapse numbers from the intact zone to the LPZ increase (green), while synapses numbers from the LPZ to the intact zone decrease (red). (B) All neurons in the intact zone (green) and most neurons in the LPZ (red) return to the homeostatic range following deafferentation. Neurons lose axonal and dendritic elements if their calcium concentration is lower than 0.1 or higher than 0.75 (dark gray background). Neurons form only dendritic elements if their calcium concentration is greater than 0.1 but lower than 0.4 (gray), and form both axonal and dendritic elements if their calcium concentration is greater 0.4 but lower than 0.65 (light gray). The homeostatic range, in which synaptic element numbers do not change, spans from 0.65 to 0.75. The diagram helps to match changes in topology with the current level of electrical activity. (C) The normalized average clustering coefficient γ of neurons in the LPZ (including connections with the entire network) decreases while neuronal activities are very low (<0.1) and increases as soon as activities of LPZ neurons are greater than 0.1. The first bump in clustering is brought about by ingrowing synapses from the intact zone into the LPZ, whereas the second rise in clustering is caused predominantly by new synapses within the LPZ, which are formed when calcium concentrations of LPZ neurons exceed 0.4. The γ of neurons in the intact zone (considering all their connections to any neuron in the entire network) decreases continuously after a temporary rise. (D) Average shortest paths from neurons in the intact zone to neurons in the LPZ show a steady decrease (green), while average path lengths from LPZ to intact zone neurons return to initial levels after a tri-phasic increase and decrease. (E) The clustering coefficient with no normalization (Equation 10) does not show a decrease for intact zone neurons as the normalized clustering coefficient γ does. (F) No differences were found between the characteristic path length and the normalized characteristic path length λ. Green curve indicates changes in clustering coefficient of intact zone neurons with the entire network. Means over five simulations per scenario. Shadings of the curves in (A,C–F) indicate standard deviations.
Mentions: From our previous work on modeling cortical rewiring after focal retinal lesions (Butz and van Ooyen, 2013), we know that functional network repair can be brought about by an, also experimentally observed, ingrowth of connections from the intact zone to the LPZ (Darian-Smith and Gilbert, 1994; Yamahachi et al., 2009). For physiological network repair to go along with functional retinotopic remapping (as shown in mice Keck et al., 2008), we found that it is important that the majority of new connections impinging on deafferentated neurons originates from intact areas and transmits electrical activity from the intact zone to the LPZ. Here, we further investigate whether the changes in global topology parameters express this ingrowth of connections. For this, we first focus on the activity-dependent changes in synapse numbers and connectivity between the intact zone and the LPZ. The first 6 weeks are dominated by a loss of synapses originating from the LPZ (Figure 4A). This is a direct consequence of neuronal activities being low and calcium concentrations being below ηA = 0.4 (Figure 4B), which causes axonal elements to be removed. By contrast, axonal elements from the intact zone form additional synapses with the LPZ right from the onset of the lesion. Between 6 and 8 weeks after the lesion, most neurons in the LPZ have reached calcium levels of 0.4 and start forming additional axonal elements, connecting to targets in the LPZ as well as the intact zone. The number of recurrent synapses from the LPZ to the LPZ does thereby at no time exceeds the number of synapses from the intact zone to the LPZ, as required for a functional remapping to emerge.

Bottom Line: Homeostatic structural plasticity postulates that neurons aim to maintain a desired level of electrical activity by deleting synapses when neuronal activity is too high and by providing new synaptic contacts when activity is too low.Using our Model of Structural Plasticity, we explored how local changes in connectivity induced by a focal loss of input affected global network topology.Furthermore, deafferentated neurons increased their global but decreased their local efficiency and got longer tailed degree distributions, indicating the emergence of hub neurons.

View Article: PubMed Central - PubMed

Affiliation: Simulation Lab Neuroscience - Bernstein Facility for Simulation and Database Technology, Institute for Advanced Simulation, Jülich Aachen Research Alliance, Forschungszentrum Jülich Jülich, Germany.

ABSTRACT
After brain lesions caused by tumors or stroke, or after lasting loss of input (deafferentation), inter- and intra-regional brain networks respond with complex changes in topology. Not only areas directly affected by the lesion but also regions remote from the lesion may alter their connectivity-a phenomenon known as diaschisis. Changes in network topology after brain lesions can lead to cognitive decline and increasing functional disability. However, the principles governing changes in network topology are poorly understood. Here, we investigated whether homeostatic structural plasticity can account for changes in network topology after deafferentation and brain lesions. Homeostatic structural plasticity postulates that neurons aim to maintain a desired level of electrical activity by deleting synapses when neuronal activity is too high and by providing new synaptic contacts when activity is too low. Using our Model of Structural Plasticity, we explored how local changes in connectivity induced by a focal loss of input affected global network topology. In accordance with experimental and clinical data, we found that after partial deafferentation, the network as a whole became more random, although it maintained its small-world topology, while deafferentated neurons increased their betweenness centrality as they rewired and returned to the homeostatic range of activity. Furthermore, deafferentated neurons increased their global but decreased their local efficiency and got longer tailed degree distributions, indicating the emergence of hub neurons. Together, our results suggest that homeostatic structural plasticity may be an important driving force for lesion-induced network reorganization and that the increase in betweenness centrality of deafferentated areas may hold as a biomarker for brain repair.

No MeSH data available.


Related in: MedlinePlus