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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.


Action potential firing pattern and discriminant analysis of electrophysiological and morphological properties of excitatory layer IV cells. (A) Representative whole cell current clamp recordings showing regular spiking (RS) and intrinsically bursting (IB) firing patterns in SERT−/− excitatory layer IV cells. Both firing patterns were observed in both genotypes (SERT+/+ and SERT−/−) as well as both morphological classes (spiny stellate cells and pyramidal cells). (B) Canonical score plots based on discriminant analysis of the genotype specific electrophysiological (upper panel) and morphological classes (lower panel) as a-priory groups. Plots were based on two functions which combined the best characteristics defining either the firing patterns (B1; function 1: high and low current 1st ISI; function 2: firing threshold, 2nd AP amplitude) and morphological classes (B2; function 1: Vrmp, high current 2nd ISI; function 2: high current 1st ISI, 2nd AP amplitude). Both analysis properties show no segregation of genotype specific populations.
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Figure 3: Action potential firing pattern and discriminant analysis of electrophysiological and morphological properties of excitatory layer IV cells. (A) Representative whole cell current clamp recordings showing regular spiking (RS) and intrinsically bursting (IB) firing patterns in SERT−/− excitatory layer IV cells. Both firing patterns were observed in both genotypes (SERT+/+ and SERT−/−) as well as both morphological classes (spiny stellate cells and pyramidal cells). (B) Canonical score plots based on discriminant analysis of the genotype specific electrophysiological (upper panel) and morphological classes (lower panel) as a-priory groups. Plots were based on two functions which combined the best characteristics defining either the firing patterns (B1; function 1: high and low current 1st ISI; function 2: firing threshold, 2nd AP amplitude) and morphological classes (B2; function 1: Vrmp, high current 2nd ISI; function 2: high current 1st ISI, 2nd AP amplitude). Both analysis properties show no segregation of genotype specific populations.

Mentions: We investigated whether the anatomical changes in the afferent TC pathways were accompanied by changes in excitability of the excitatory layer IV neurons. We used whole cell patch clamp recordings to investigate both passive and active intrinsic membrane properties following a sustained current injection in cells of both genotype (SERT+/+: n = 32, SERT−/−: n = 41). A summary of the most relevant intrinsic electrophysiological properties recorded is given in Table 2. In agreement with previous studies, (Chagnac-Amitai and Connors, 1989; Feldmeyer et al., 1999; Schubert et al., 2003; Staiger et al., 2004) in SERT+/+ rats, excitatory layer IV neurons were classified as being either regular spiking (RS; n = 16) or intrinsically burst spiking (IB; n = 16; Figure 3A). IB cells differed from RS cells most prominently in (i) eliciting an initial doublet or triplet of APs riding upon a depolarizing envelope at just suprathreshold stimulation, (ii) showing significantly shorter 1st inter-spike intervals (RS: 46.1 ± 2.1 ms; IB: 11.1 ± 4.3 ms; p < 0.001), and (iii) a reduced 2nd AP amplitude (RS: 69.2 ± 2.3; IB: 55.6 ± 2.3; p < 0.001). Across all neurons morphologically identified as SpSt cells or pyramidal cells, the two firing patterns were equally distributed (Table 2).


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)

Action potential firing pattern and discriminant analysis of electrophysiological and morphological properties of excitatory layer IV cells. (A) Representative whole cell current clamp recordings showing regular spiking (RS) and intrinsically bursting (IB) firing patterns in SERT−/− excitatory layer IV cells. Both firing patterns were observed in both genotypes (SERT+/+ and SERT−/−) as well as both morphological classes (spiny stellate cells and pyramidal cells). (B) Canonical score plots based on discriminant analysis of the genotype specific electrophysiological (upper panel) and morphological classes (lower panel) as a-priory groups. Plots were based on two functions which combined the best characteristics defining either the firing patterns (B1; function 1: high and low current 1st ISI; function 2: firing threshold, 2nd AP amplitude) and morphological classes (B2; function 1: Vrmp, high current 2nd ISI; function 2: high current 1st ISI, 2nd AP amplitude). Both analysis properties show no segregation of genotype specific populations.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Action potential firing pattern and discriminant analysis of electrophysiological and morphological properties of excitatory layer IV cells. (A) Representative whole cell current clamp recordings showing regular spiking (RS) and intrinsically bursting (IB) firing patterns in SERT−/− excitatory layer IV cells. Both firing patterns were observed in both genotypes (SERT+/+ and SERT−/−) as well as both morphological classes (spiny stellate cells and pyramidal cells). (B) Canonical score plots based on discriminant analysis of the genotype specific electrophysiological (upper panel) and morphological classes (lower panel) as a-priory groups. Plots were based on two functions which combined the best characteristics defining either the firing patterns (B1; function 1: high and low current 1st ISI; function 2: firing threshold, 2nd AP amplitude) and morphological classes (B2; function 1: Vrmp, high current 2nd ISI; function 2: high current 1st ISI, 2nd AP amplitude). Both analysis properties show no segregation of genotype specific populations.
Mentions: We investigated whether the anatomical changes in the afferent TC pathways were accompanied by changes in excitability of the excitatory layer IV neurons. We used whole cell patch clamp recordings to investigate both passive and active intrinsic membrane properties following a sustained current injection in cells of both genotype (SERT+/+: n = 32, SERT−/−: n = 41). A summary of the most relevant intrinsic electrophysiological properties recorded is given in Table 2. In agreement with previous studies, (Chagnac-Amitai and Connors, 1989; Feldmeyer et al., 1999; Schubert et al., 2003; Staiger et al., 2004) in SERT+/+ rats, excitatory layer IV neurons were classified as being either regular spiking (RS; n = 16) or intrinsically burst spiking (IB; n = 16; Figure 3A). IB cells differed from RS cells most prominently in (i) eliciting an initial doublet or triplet of APs riding upon a depolarizing envelope at just suprathreshold stimulation, (ii) showing significantly shorter 1st inter-spike intervals (RS: 46.1 ± 2.1 ms; IB: 11.1 ± 4.3 ms; p < 0.001), and (iii) a reduced 2nd AP amplitude (RS: 69.2 ± 2.3; IB: 55.6 ± 2.3; p < 0.001). Across all neurons morphologically identified as SpSt cells or pyramidal cells, the two firing patterns were equally distributed (Table 2).

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.