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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

Somatodendritic organization of excitatory spiny stellate (A,C) and pyramidal (B,D) cells in SERT+/+ and SERT−/− layer IV barrel cortex. Micrographs of a biocytin stained spiny stellate (A) and pyramidal (B) cells in acute slice and representative morphological reconstructions; spiny stellate (C) and pyramidal (D) of both genotypes. Gray shaded areas indicate the position of the respective home barrel.
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Figure 4: Somatodendritic organization of excitatory spiny stellate (A,C) and pyramidal (B,D) cells in SERT+/+ and SERT−/− layer IV barrel cortex. Micrographs of a biocytin stained spiny stellate (A) and pyramidal (B) cells in acute slice and representative morphological reconstructions; spiny stellate (C) and pyramidal (D) of both genotypes. Gray shaded areas indicate the position of the respective home barrel.

Mentions: We next investigated the detailed dendritic and axonal morphology of both classes of layer IV excitatory cells using a quantitative morphometric analysis. In the normally developed barrel cortex, layer IV excitatory neurons, and in particular SpSt cells, the dendritic and axonal organization is strongly aligned with the respective HB and its associated cortical column. We performed 3-D reconstructions of a total of 50 electrophysiologically classified and biocytin labeled neurons for somatodendritic morphological quantification (SERT+/+: SpSt: n = 10, Pyr: n = 12 and SERT−/−: SpSt: n = 13, Pyr: n = 15). Additionally we reconstructed the axon in cells where (i) the collaterals were well preserved and stained and (ii) the main descending axon remained uncut at least until it reached the deeper layer Vb of the barrel cortex (SERT+/+: SpSt: n = 7, Pyr: n = 6 and SERT−/−:SpSt: n = 5, Pyr: n = 9). Representative reconstructions and overlays of SpSt and Pyr cells are shown in Figures 4 and 5.


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)

Somatodendritic organization of excitatory spiny stellate (A,C) and pyramidal (B,D) cells in SERT+/+ and SERT−/− layer IV barrel cortex. Micrographs of a biocytin stained spiny stellate (A) and pyramidal (B) cells in acute slice and representative morphological reconstructions; spiny stellate (C) and pyramidal (D) of both genotypes. Gray shaded areas indicate the position of the respective home barrel.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Somatodendritic organization of excitatory spiny stellate (A,C) and pyramidal (B,D) cells in SERT+/+ and SERT−/− layer IV barrel cortex. Micrographs of a biocytin stained spiny stellate (A) and pyramidal (B) cells in acute slice and representative morphological reconstructions; spiny stellate (C) and pyramidal (D) of both genotypes. Gray shaded areas indicate the position of the respective home barrel.
Mentions: We next investigated the detailed dendritic and axonal morphology of both classes of layer IV excitatory cells using a quantitative morphometric analysis. In the normally developed barrel cortex, layer IV excitatory neurons, and in particular SpSt cells, the dendritic and axonal organization is strongly aligned with the respective HB and its associated cortical column. We performed 3-D reconstructions of a total of 50 electrophysiologically classified and biocytin labeled neurons for somatodendritic morphological quantification (SERT+/+: SpSt: n = 10, Pyr: n = 12 and SERT−/−: SpSt: n = 13, Pyr: n = 15). Additionally we reconstructed the axon in cells where (i) the collaterals were well preserved and stained and (ii) the main descending axon remained uncut at least until it reached the deeper layer Vb of the barrel cortex (SERT+/+: SpSt: n = 7, Pyr: n = 6 and SERT−/−:SpSt: n = 5, Pyr: n = 9). Representative reconstructions and overlays of SpSt and Pyr cells are shown in Figures 4 and 5.

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