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High serotonin levels during brain development alter the structural input-output connectivity of neural networks in the rat somatosensory layer IV.

Miceli S, Negwer M, van Eijs F, Kalkhoven C, van Lierop I, Homberg J, Schubert D - Front Cell Neurosci (2013)

Bottom Line: Despite the presence of multiple genetic models, the effect of high extracellular 5-HT levels on the structure and function of developing intracortical neural networks is far from being understood.Our results confirmed previous findings that high levels of 5-HT during development lead to a reduction of the topographical precision of TCA projections toward the barrel cortex.In layer IV, both excitatory SpSt and pyramidal cells showed a significantly reduced intracolumnar organization of their axonal projections.

View Article: PubMed Central - PubMed

Affiliation: Department of Cognitive Neuroscience, Centre for Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Nijmegen Medical Centre Nijmegen, Netherlands.

ABSTRACT
Homeostatic regulation of serotonin (5-HT) concentration is critical for "normal" topographical organization and development of thalamocortical (TC) afferent circuits. Down-regulation of the serotonin transporter (SERT) and the consequent impaired reuptake of 5-HT at the synapse, results in a reduced terminal branching of developing TC afferents within the primary somatosensory cortex (S1). Despite the presence of multiple genetic models, the effect of high extracellular 5-HT levels on the structure and function of developing intracortical neural networks is far from being understood. Here, using juvenile SERT knockout (SERT(-/-)) rats we investigated, in vitro, the effect of increased 5-HT levels on the structural organization of (i) the TC projections of the ventroposteromedial thalamic nucleus toward S1, (ii) the general barrel-field pattern, and (iii) the electrophysiological and morphological properties of the excitatory cell population in layer IV of S1 [spiny stellate (SpSt) and pyramidal cells]. Our results confirmed previous findings that high levels of 5-HT during development lead to a reduction of the topographical precision of TCA projections toward the barrel cortex. Also, the barrel pattern was altered but not abolished in SERT(-/-) rats. In layer IV, both excitatory SpSt and pyramidal cells showed a significantly reduced intracolumnar organization of their axonal projections. In addition, the layer IV SpSt cells gave rise to a prominent projection toward the infragranular layer Vb. Our findings point to a structural and functional reorganization of TCAs, as well as early stage intracortical microcircuitry, following the disruption of 5-HT reuptake during critical developmental periods. The increased projection pattern of the layer IV neurons suggests that the intracortical network changes are not limited to the main entry layer IV but may also affect the subsequent stages of the canonical circuits of the barrel cortex.

No MeSH data available.


Related in: MedlinePlus

Quantitative analysis of the axonal projection pattern of excitatory spiny stellate (A) and pyramidal cells (B) in SERT+/+ and SERT−/− layer IV barrel cortex. Schematic drawings (left panels) illustrate the significant changes in relative bouton distribution within the individual layers (I–VI), highlighting layers specific shifts from home column (HC) to septal or neighboring column (NC) and vice versa. Histograms (right panels) represent the most relevant layer specific axonal properties (length, nodes, and boutons number) per genotype. Data are mean ± SEM, asterisks mark significant differences between genotypes. *P < 0.05; **P < 0.01.
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Figure 6: Quantitative analysis of the axonal projection pattern of excitatory spiny stellate (A) and pyramidal cells (B) in SERT+/+ and SERT−/− layer IV barrel cortex. Schematic drawings (left panels) illustrate the significant changes in relative bouton distribution within the individual layers (I–VI), highlighting layers specific shifts from home column (HC) to septal or neighboring column (NC) and vice versa. Histograms (right panels) represent the most relevant layer specific axonal properties (length, nodes, and boutons number) per genotype. Data are mean ± SEM, asterisks mark significant differences between genotypes. *P < 0.05; **P < 0.01.

Mentions: Our results show that while the length of the axonal projections as well as total number of boutons remained unchanged in SERT−/− SpSt and pyramidal cells, the axonal pattern underwent significant cell type specific redistributions (p < 0.0001, ANOVA; Figures 6A,B). Whereas in SERT+/+ SpSt, 93% of the axon, 97% of the nodes and 94% of the boutons were found in the HC, in SERT−/− rat SpSt only 68% of the axon, 79% of the nodes and 69% of the boutons were found in this compartment (p < 0.001, p = 0.002, p < 0.001, respectively). These redistributions of the axon projections from the HC toward septal and NCs were most prominent in the granular and supragranular layers. There, the axon collaterals established significantly more boutons, while bouton numbers in the respective layers of the HC were reduced (Figure 6A). This reduction in HC layer II/III of SERT−/− rats mainly resulted from fewer axonal projections into the upper layer II/III, where axonal length and bouton numbers were halved (p = 0.042 and p = 0.048, respectively). Furthermore, we found that in SERT−/− SpSt cells, all parameters of axonal projections toward the infragranular layer Vb of the HC were significantly increased by 2–3-fold, i.e., axon length (SERT+/+: 539 ± 149 μm; SERT−/−: 1805 ± 254 μm; p = 0.001) arborizations (number of nodes; SERT+/+: 1.7 ± 0.6; SERT−/−: 13.0 ± 1.7; P = 0.002) and bouton numbers (SERT+/+: 104 ± 32; SERT−/−: 333 ± 71; p = 0.009).


High serotonin levels during brain development alter the structural input-output connectivity of neural networks in the rat somatosensory layer IV.

Miceli S, Negwer M, van Eijs F, Kalkhoven C, van Lierop I, Homberg J, Schubert D - Front Cell Neurosci (2013)

Quantitative analysis of the axonal projection pattern of excitatory spiny stellate (A) and pyramidal cells (B) in SERT+/+ and SERT−/− layer IV barrel cortex. Schematic drawings (left panels) illustrate the significant changes in relative bouton distribution within the individual layers (I–VI), highlighting layers specific shifts from home column (HC) to septal or neighboring column (NC) and vice versa. Histograms (right panels) represent the most relevant layer specific axonal properties (length, nodes, and boutons number) per genotype. Data are mean ± SEM, asterisks mark significant differences between genotypes. *P < 0.05; **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3675331&req=5

Figure 6: Quantitative analysis of the axonal projection pattern of excitatory spiny stellate (A) and pyramidal cells (B) in SERT+/+ and SERT−/− layer IV barrel cortex. Schematic drawings (left panels) illustrate the significant changes in relative bouton distribution within the individual layers (I–VI), highlighting layers specific shifts from home column (HC) to septal or neighboring column (NC) and vice versa. Histograms (right panels) represent the most relevant layer specific axonal properties (length, nodes, and boutons number) per genotype. Data are mean ± SEM, asterisks mark significant differences between genotypes. *P < 0.05; **P < 0.01.
Mentions: Our results show that while the length of the axonal projections as well as total number of boutons remained unchanged in SERT−/− SpSt and pyramidal cells, the axonal pattern underwent significant cell type specific redistributions (p < 0.0001, ANOVA; Figures 6A,B). Whereas in SERT+/+ SpSt, 93% of the axon, 97% of the nodes and 94% of the boutons were found in the HC, in SERT−/− rat SpSt only 68% of the axon, 79% of the nodes and 69% of the boutons were found in this compartment (p < 0.001, p = 0.002, p < 0.001, respectively). These redistributions of the axon projections from the HC toward septal and NCs were most prominent in the granular and supragranular layers. There, the axon collaterals established significantly more boutons, while bouton numbers in the respective layers of the HC were reduced (Figure 6A). This reduction in HC layer II/III of SERT−/− rats mainly resulted from fewer axonal projections into the upper layer II/III, where axonal length and bouton numbers were halved (p = 0.042 and p = 0.048, respectively). Furthermore, we found that in SERT−/− SpSt cells, all parameters of axonal projections toward the infragranular layer Vb of the HC were significantly increased by 2–3-fold, i.e., axon length (SERT+/+: 539 ± 149 μm; SERT−/−: 1805 ± 254 μm; p = 0.001) arborizations (number of nodes; SERT+/+: 1.7 ± 0.6; SERT−/−: 13.0 ± 1.7; P = 0.002) and bouton numbers (SERT+/+: 104 ± 32; SERT−/−: 333 ± 71; p = 0.009).

Bottom Line: Despite the presence of multiple genetic models, the effect of high extracellular 5-HT levels on the structure and function of developing intracortical neural networks is far from being understood.Our results confirmed previous findings that high levels of 5-HT during development lead to a reduction of the topographical precision of TCA projections toward the barrel cortex.In layer IV, both excitatory SpSt and pyramidal cells showed a significantly reduced intracolumnar organization of their axonal projections.

View Article: PubMed Central - PubMed

Affiliation: Department of Cognitive Neuroscience, Centre for Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Nijmegen Medical Centre Nijmegen, Netherlands.

ABSTRACT
Homeostatic regulation of serotonin (5-HT) concentration is critical for "normal" topographical organization and development of thalamocortical (TC) afferent circuits. Down-regulation of the serotonin transporter (SERT) and the consequent impaired reuptake of 5-HT at the synapse, results in a reduced terminal branching of developing TC afferents within the primary somatosensory cortex (S1). Despite the presence of multiple genetic models, the effect of high extracellular 5-HT levels on the structure and function of developing intracortical neural networks is far from being understood. Here, using juvenile SERT knockout (SERT(-/-)) rats we investigated, in vitro, the effect of increased 5-HT levels on the structural organization of (i) the TC projections of the ventroposteromedial thalamic nucleus toward S1, (ii) the general barrel-field pattern, and (iii) the electrophysiological and morphological properties of the excitatory cell population in layer IV of S1 [spiny stellate (SpSt) and pyramidal cells]. Our results confirmed previous findings that high levels of 5-HT during development lead to a reduction of the topographical precision of TCA projections toward the barrel cortex. Also, the barrel pattern was altered but not abolished in SERT(-/-) rats. In layer IV, both excitatory SpSt and pyramidal cells showed a significantly reduced intracolumnar organization of their axonal projections. In addition, the layer IV SpSt cells gave rise to a prominent projection toward the infragranular layer Vb. Our findings point to a structural and functional reorganization of TCAs, as well as early stage intracortical microcircuitry, following the disruption of 5-HT reuptake during critical developmental periods. The increased projection pattern of the layer IV neurons suggests that the intracortical network changes are not limited to the main entry layer IV but may also affect the subsequent stages of the canonical circuits of the barrel cortex.

No MeSH data available.


Related in: MedlinePlus