Table 1.
Model name | Manipulation/Gene affected | Duration | Effect on extracellular brain 5-HT concentration | Effects on TCAs (prenatal) | Effects on BF (postnatal) | References |
---|---|---|---|---|---|---|
PCPA | Pharmacological blocker of TPH1/2; inhibits 5-HT synthesis non-specifically | P0–P10 | Decrease | n.d. | - Reduction of BF areas in cortical layer IV (S1) - Delayed barrel pattern maturation |
(Persico et al., 2000) |
MAOA-KO | MAOA gene not functional; decreased 5-HT degradation | Lifelong | Increase | n.d. | - PMBSF and AS fused - BF surface area in S1 enlarged by 20%. |
(Cases et al., 1995; Cases et al., 1996; Rebsam et al., 2002) |
SERT-KO | SERT (slc6a4) gene knockout; reduced 5-HT uptake | Lifelong | Increase | n.d. | - Only few PMBSF barrels visible - Thinning of cortical layer IV - Altered cortical development |
(Persico et al., 2001; Altamura et al., 2007; Murphy & Lesch, 2008) |
VMAT2-KO | VMAT2 (slc18a2) gene knockout; reduced intracellular 5-HT uptake. | Lifelong (die at P5) | Decrease | n.d. | - Delayed emergence of barrel patterning - Development of upper cortical layers severely delayed |
(Persico et al., 2001; Alvarez et al., 2002) |
TPH2-KO | TPH-2 gene knockout; no central 5-HT synthesis | Lifelong | Decrease (CNS only) | n.d. | Normal | (Gutknecht et al., 2008) |
Pet1-KO | Pet1 gene knockout; 80% of 5-HT neurons fail to differentiate | Lifelong | Decrease (CNS/PNS) | Normal | Normal at P7 (see Fig. 1) | Gaspar, unpublished observations |
5-HT1B-KO | 5-HT1B (htr1b) gene knockout; reduced 5-HT signaling in subsets of neurons (incl. thal/raphe). | Lifelong | n.d. (decreased 5-HT signaling) | n.d. | normal | (Salichon et al., 2001) |
5-HT1B/D- in utero electro-poration | In utero electroporation of 5-HT1B/1D receptors siRNAs; decreased both receptor expression | E12.5–E18.5 | n.d. (decreased 5-HT signaling in thalamic neurons only) | Ventrolateral shift of TCAs in IC and cortex | n.d. | (Bonnin et al., 2007) |
5-HT1B/D- in utero electro-poration | In utero electroporation of 5-HT1B/1D receptors expression plasmids; increased both receptor expression | E12.5–E18.5 | n.d. (increased 5-HT signaling in thalamic neurons only) | Dorsomedial shift of TCAs in IC and cortex | n.d. | (Bonnin et al., 2007) |