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Functional and structural specific roles of activity-driven BDNF within circuits formed by single spiny stellate neurons of the barrel cortex.

Sun QQ, Zhang Z, Sun J, Nair AS, Petrus DP, Zhang C - Front Cell Neurosci (2014)

Bottom Line: However, it is unclear how specific BDNF's effects are on different circuit components.The effects on GABA transmission occurs via presynaptic alteration of calcium-dependent release probability.These results suggest that neuronal activity through activity-driven BDNF expression, can selectively regulate specific features of layer IV circuits in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology and Physiology, University of Wyoming, Laramie, WY USA.

ABSTRACT
Brain derived neurotrophic factor (BDNF) plays key roles in several neurodevelopmental disorders and actions of pharmacological treatments. However, it is unclear how specific BDNF's effects are on different circuit components. Current studies have largely focused on the role of BDNF in modification of synaptic development. The precise roles of BDNF in the refinement of a functional circuit in vivo remain unclear. Val66Met polymorphism of BDNF may be associated with increased risk for cognitive impairments and is mediated at least in part by activity-dependent trafficking and/or secretion of BDNF. Using mutant mice that lacked activity-driven BDNF expression (bdnf-KIV), we previously reported that experience regulation of the cortical GABAergic network is mediated by activity-driven BDNF expression. Here, we demonstrate that activity-driven BDNF's effects on circuits formed by the layer IV spiny stellate cells are highly specific. Structurally, dendritic but not axonal morphology was altered in the mutant. Physiologically, GABAergic but not glutamatergic synapses were severely affected. The effects on GABA transmission occurs via presynaptic alteration of calcium-dependent release probability. These results suggest that neuronal activity through activity-driven BDNF expression, can selectively regulate specific features of layer IV circuits in vivo. We postulate that the role of activity-dependent BDNF is to modulate the computational ability of circuits that relate to the gain control (i.e., feed-forward inhibition); whereas the basic wiring of circuits relevant to the sensory pathway is spared. Gain control modulation within cortical circuits has broad impact on cognitive processing and brain state-transitions. Cognitive behavior and mode is determined by brain states, thus the studying of circuit alteration by endogenous BDNF provides insights into the cellular and molecular mechanisms of diseases mediated by BDNF.

No MeSH data available.


Related in: MedlinePlus

Axonal morphology was unaltered in KIV-/- mice. (A) An example of a pair of reconstructed wild-type spiny stellate cells, located in neighboring barrels (grey areas in A2 and red contour in A1). Note the typical distribution of axonal arbors (blue) within layer IV barrels with projections toward layer II/III, and downward projections toward the white matter. Dendrites (magenta) are largely confined within a single barrel. (B) Reconstructed axonal arbors from 9 pairs of wild-type (B1, black) and littermate mutant neurons (B2, red) were superimposed at the soma location. (C) Sholl analysis was performed to compare the distribution of no. of intersections (C1), and the distribution of total axonal length (C2) along different radius from the soma in 21 wild-type and 10 mutant neurons, respectively. No statistical differences between WT and KIV mice.
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Figure 4: Axonal morphology was unaltered in KIV-/- mice. (A) An example of a pair of reconstructed wild-type spiny stellate cells, located in neighboring barrels (grey areas in A2 and red contour in A1). Note the typical distribution of axonal arbors (blue) within layer IV barrels with projections toward layer II/III, and downward projections toward the white matter. Dendrites (magenta) are largely confined within a single barrel. (B) Reconstructed axonal arbors from 9 pairs of wild-type (B1, black) and littermate mutant neurons (B2, red) were superimposed at the soma location. (C) Sholl analysis was performed to compare the distribution of no. of intersections (C1), and the distribution of total axonal length (C2) along different radius from the soma in 21 wild-type and 10 mutant neurons, respectively. No statistical differences between WT and KIV mice.

Mentions: Intracortical axonal collaterals between layer IV cells contribute profusely to the excitatory synaptic inputs in spiny stellate cells (Feldmeyer et al., 1999). The morphological analysis of axonal arbors was based on 31 neurobiotin labeled, relatively intact layer IV spiny stellate cells. These consisted of 9 out of 21 wild-type neurons (KIV+/+) and 9 out of 10 mutant neurons (KIV-/-) that were located at least 100 μm below the surface of a 350 μm brain slice. The axonal arbors of both the mutant and wild-type spiny stellate cells showed typical patterns as previously described (Staiger et al., 2004; Egger et al., 2008). Briefly, the main stem of axons originated from the basal direction of the soma and extended toward the white matter. Within layer IV, the main stem of axons gave rise to abundant recurrent collaterals that centered on the barrels and extended to layer II/III barrels (Figure 4A). Cells with truncated axonal arbors, i.e., severe deviation from the typical axonal morphology, were removed from analysis. The morphometric data and Sholl analysis showed that there were no significant differences in either aspects of axonal morphologies, which include both the total length and the branching patterns (Table 2; Figures 4B,C). Therefore, in contrast to the dendrites, the morphology of axonal arbors of spiny stellate cells is independent of the activity-driven BDNF expression. The basal level of BDNF expression is therefore sufficient to the development and maintenance of intact axonal arbors in these cells.


Functional and structural specific roles of activity-driven BDNF within circuits formed by single spiny stellate neurons of the barrel cortex.

Sun QQ, Zhang Z, Sun J, Nair AS, Petrus DP, Zhang C - Front Cell Neurosci (2014)

Axonal morphology was unaltered in KIV-/- mice. (A) An example of a pair of reconstructed wild-type spiny stellate cells, located in neighboring barrels (grey areas in A2 and red contour in A1). Note the typical distribution of axonal arbors (blue) within layer IV barrels with projections toward layer II/III, and downward projections toward the white matter. Dendrites (magenta) are largely confined within a single barrel. (B) Reconstructed axonal arbors from 9 pairs of wild-type (B1, black) and littermate mutant neurons (B2, red) were superimposed at the soma location. (C) Sholl analysis was performed to compare the distribution of no. of intersections (C1), and the distribution of total axonal length (C2) along different radius from the soma in 21 wild-type and 10 mutant neurons, respectively. No statistical differences between WT and KIV mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222225&req=5

Figure 4: Axonal morphology was unaltered in KIV-/- mice. (A) An example of a pair of reconstructed wild-type spiny stellate cells, located in neighboring barrels (grey areas in A2 and red contour in A1). Note the typical distribution of axonal arbors (blue) within layer IV barrels with projections toward layer II/III, and downward projections toward the white matter. Dendrites (magenta) are largely confined within a single barrel. (B) Reconstructed axonal arbors from 9 pairs of wild-type (B1, black) and littermate mutant neurons (B2, red) were superimposed at the soma location. (C) Sholl analysis was performed to compare the distribution of no. of intersections (C1), and the distribution of total axonal length (C2) along different radius from the soma in 21 wild-type and 10 mutant neurons, respectively. No statistical differences between WT and KIV mice.
Mentions: Intracortical axonal collaterals between layer IV cells contribute profusely to the excitatory synaptic inputs in spiny stellate cells (Feldmeyer et al., 1999). The morphological analysis of axonal arbors was based on 31 neurobiotin labeled, relatively intact layer IV spiny stellate cells. These consisted of 9 out of 21 wild-type neurons (KIV+/+) and 9 out of 10 mutant neurons (KIV-/-) that were located at least 100 μm below the surface of a 350 μm brain slice. The axonal arbors of both the mutant and wild-type spiny stellate cells showed typical patterns as previously described (Staiger et al., 2004; Egger et al., 2008). Briefly, the main stem of axons originated from the basal direction of the soma and extended toward the white matter. Within layer IV, the main stem of axons gave rise to abundant recurrent collaterals that centered on the barrels and extended to layer II/III barrels (Figure 4A). Cells with truncated axonal arbors, i.e., severe deviation from the typical axonal morphology, were removed from analysis. The morphometric data and Sholl analysis showed that there were no significant differences in either aspects of axonal morphologies, which include both the total length and the branching patterns (Table 2; Figures 4B,C). Therefore, in contrast to the dendrites, the morphology of axonal arbors of spiny stellate cells is independent of the activity-driven BDNF expression. The basal level of BDNF expression is therefore sufficient to the development and maintenance of intact axonal arbors in these cells.

Bottom Line: However, it is unclear how specific BDNF's effects are on different circuit components.The effects on GABA transmission occurs via presynaptic alteration of calcium-dependent release probability.These results suggest that neuronal activity through activity-driven BDNF expression, can selectively regulate specific features of layer IV circuits in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology and Physiology, University of Wyoming, Laramie, WY USA.

ABSTRACT
Brain derived neurotrophic factor (BDNF) plays key roles in several neurodevelopmental disorders and actions of pharmacological treatments. However, it is unclear how specific BDNF's effects are on different circuit components. Current studies have largely focused on the role of BDNF in modification of synaptic development. The precise roles of BDNF in the refinement of a functional circuit in vivo remain unclear. Val66Met polymorphism of BDNF may be associated with increased risk for cognitive impairments and is mediated at least in part by activity-dependent trafficking and/or secretion of BDNF. Using mutant mice that lacked activity-driven BDNF expression (bdnf-KIV), we previously reported that experience regulation of the cortical GABAergic network is mediated by activity-driven BDNF expression. Here, we demonstrate that activity-driven BDNF's effects on circuits formed by the layer IV spiny stellate cells are highly specific. Structurally, dendritic but not axonal morphology was altered in the mutant. Physiologically, GABAergic but not glutamatergic synapses were severely affected. The effects on GABA transmission occurs via presynaptic alteration of calcium-dependent release probability. These results suggest that neuronal activity through activity-driven BDNF expression, can selectively regulate specific features of layer IV circuits in vivo. We postulate that the role of activity-dependent BDNF is to modulate the computational ability of circuits that relate to the gain control (i.e., feed-forward inhibition); whereas the basic wiring of circuits relevant to the sensory pathway is spared. Gain control modulation within cortical circuits has broad impact on cognitive processing and brain state-transitions. Cognitive behavior and mode is determined by brain states, thus the studying of circuit alteration by endogenous BDNF provides insights into the cellular and molecular mechanisms of diseases mediated by BDNF.

No MeSH data available.


Related in: MedlinePlus