Effect of serotonin depletion on vibrissa-related patterns of thalamic afferents in the rat's somatosensory cortex

Abstract

To investigate the role of 5-HT in the development of the somatosensory cortex, this amine was depleted in newborn (P-0) rats with a single subcutaneous injection of the toxin 5,7-dihydroxytryptamine (5,7-DHT) and thalamocortical organization was assayed by application of the carbocyanine dye Di-I to the thalamocortical radiations or ventrobasal thalamus, or by staining cortical sections for AChE or cytochrome oxidase (CO). High-performance liquid chromatographic analysis of cortices from animals killed on P-6 or P > 60 demonstrated that 5,7-DHT treatment resulted in 85.04 +/- 12.6% and 72.5 +/- 1.5% reductions in cortical 5-HT, respectively. Alternate cortices from the brains of animals killed on P-6 processed for 5-HT immunoreactivity demonstrated a complete absence of the vibrissa-related pattern of immunoreactivity and only a small number of coarse immunoreactive axons. The 85% depletion of 5-HT did not alter the somatotopic organization of thalamocortical afferents in animals killed on P-6 or P > 60, but it did cause 30.5 +/- 7.3% and 19.1 +/- 3.7% reductions in the cross-sectional areas of the patches of thalamocortical afferents corresponding to the long mystacial vibrissae (p < 0.05). These reductions were not associated with significant reductions in either brain or cortical weight or with decreases in the dimensions of the thalamic representation of the vibrissa follicles. These results indicate that 5-HT plays a significant role in the development of the thalamic innervation of the primary somatosensory cortex.

Neonatal serotonin depletion alters behavioral responses to spatial change and novelty

“…Lesion induced 5-HT innervation decreases were most dramatic in frontal cortex, a region that ordinarily contains a high density of 5-HT afferents from the raphe nuclei (Molliver, 1987;Molliver et al, 1990;Mamounas et al, 1991;Dori et al, 1996;Donovan et al, 2002). Remnants of 5-HT patches in layer IV of somatosensory cortex remained at PND 7, indicating that sequestration of serotonin by thalamocortical axons (Bennett-Clarke et al, 1991;Bennett-Clarke et al, 1994;Lebrand et al, 1996;Bennett-Clarke et al, 1997;Bruning and Liangos, 1997;Mansour-Robaey et al, 1998;Boylan et al, 2000a) persists after the neonatal 5,7-DHT lesions, despite the substantial reductions in cortical 5-HT innervation. Accumulation of 5-HT into thalamocortical terminals via SERT is likely the reason that citalopram binding was only mildly reduced in PND 7 and PND 15 mice after the lesion.…”

“…In cerebral cortical development, early manipulations of the serotonergic innervation lead to altered development and plasticity in sensory areas in a variety of species (Gu and Singer, 1995;Osterheld-Haas and Hornung, 1996;Janusonis et al, 2004). In rat, neonatal systemic depletion of the cortical serotonergic innervation delays thalamocortical patterning (Blue et al, 1991) and diminishes the size of the barrel field area during the first postnatal week (Bennett-Clarke et al, 1994). Interestingly, increased serotonin neurotransmission during the critical period also alters barrel field development (Vitalis et al, 1998;Boylan et al, 2000b;Salichon et al, 2001).…”

Barrel Pattern Formation Requires Serotonin Uptake by Thalamocortical Afferents, and Not Vesicular Monoamine Release

“…The rodent somatosensory cortex lends itself to assessments of 5-HT roles in neocortical development and plasticity, because of its one-to-one correspondence between each whisker on the snout of the animal and its barrel-like representation in the somatosensory cortex (for review, see Killackey et al, 1995;Rice, 1995). Pharmacologically induced 5-HT depletion at birth yields smaller barrels, but does not prevent the formation of the barrel pattern itself (Blue et al, 1991;Bennett-Clarke et al, 1994b;OsterheldHaas et al, 1994). Instead, excess of extracellular 5-HT in monoamine oxidase (MAO)-A knock-out (ko) mice results in the complete absence of cortical barrel patterns, as shown by Nissl or cytochrome oxidase (CO) staining.…”

Role of altered brain serotonin mechanisms in autism

“…Depletion of serotonin delays the development of the barrel fields of the rat somatosensory cortex 7,8 and decreases the size of the barrel fields. 9 Conversely, increased serotonin during this critical period, as in the monoamine oxidase A (MAOA) knock-out mouse, results in increased tangential arborization of these axons resulting in blurring of the boundaries of the cortical barrels. 10 Expression of a polymorphism of the serotonin transporter in autism 11,12 may result in altered serotonin modulation of thalamo-cortical connectivity, thus possibly accounting for abnormal sensory perception reported in many autistic subjects.…”

“…13 Decreased or increased brain serotonin during this period of development results in disruption of synaptic connectivity in sensory cortices. 4,9,10 The effect of serotonin on synaptogenesis is not limited to the sensory cortices. For example, Yan et al 14 have reported that depletion of serotonin with PCA or 5,7-dihydroxytryptamine in neonatal rat pups resulted in large decreases in the numbers of dendritic spines in hippocampus.…”