Quantified distribution of serotonin transporter and receptors during the postnatal development of the rat barrel field cortex

Mansour-Robaey, S; Mechawar, Naguib; Radja, Fatiha; Beaulieu, Clermont; Descarries, Laurent

doi:10.1016/s0165-3806(98)00016-9

Cited by 48 publications

(39 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Afferent inputs from the whiskers or vibrissae of multiple rodent species form a highly organized and topographic map from the periphery to brainstem, thalamus and finally to layer IV of SI [14,48,54,68,105,108,116,121,127]. In the early postnatal period, serotonin immunoreactivity, 5-HT 1B receptors and SERT each assume a transient pattern localized to layer IV thalamocortical axons [9,10,12,18,26,41,74,76,83,99]. Multiple studies have revealed that manipulation of early 5-HT levels results in significant alterations in the layer IV representations of the rat's whiskers [11,15,16,23,117].…”

Section: Discussionmentioning

confidence: 99%

Modeling early cortical serotonergic deficits in autism

Boylan

Blue

Höhmann

2007

Behavioural Brain Research

View full text Add to dashboard Cite

Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro-and macroscopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas.

show abstract

Section: Discussionmentioning

confidence: 99%

Modeling early cortical serotonergic deficits in autism

Boylan

Blue

Höhmann

2007

Behavioural Brain Research

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: Selective Serotonergic Depletionsmentioning

confidence: 99%

“…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). The importance of serotonin in thalamocortical maturation is underscored by the transient expression of the high affinity serotonin uptake sites (SERTs), and the 5-HT1B receptor in thalamocortical afferents in the barrel field area during the first postnatal weeks (Bennett-Clarke et al, 1991;Bennett-Clarke et al, 1993;Bruning and Liangos, 1997;Hansson et al, 1998;Lebrand et al, 1998;Mansour-Robaey et al, 1998). Disruptions of SERTs in neonatal development lead to abnormal thalamocortical connectivity (Xu et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…Disruptions of SERTs in neonatal development lead to abnormal thalamocortical connectivity (Xu et al, 2004). Serotonergic 5-HT2A receptors also are transiently over-expressed in the barrel field and have been implicated in the trophic actions of serotonin (Mansour-Robaey et al, 1998) that are observed in cultured thalamic neurons (Lieske et al, 1999). Serotonergic effects on dendritic and spine growth are not limited to the barrel field of the somatosensory cortex.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neonatal serotonin depletion alters behavioral responses to spatial change and novelty

et al. 2007

View full text Add to dashboard Cite

Multiple brain disorders that show serotonergic imbalances have a developmental onset. Experimental models indicate a role for serotonin as a morphogen in brain development. To selectively study the effects of serotonin depletions on cortical structural development and subsequent behavior, we developed a mouse model in which a serotonin neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), is injected into the medial forebrain bundle (mfb) on the day of birth. Littermates with saline injections into the mfb and age matched mice served as controls. This study characterized the extent and duration of serotonergic denervation after the selective neonatal lesion and investigated effects on exploratory behavior, spatial learning and anxiety in mice of both sexes. We report significant decreases in the serotonergic (5-HT) innervation to cortex and hippocampus, but not to subcortical forebrain structures in 5,7-DHT-lesioned mice. The depletion of 5-HT fibers in cortical areas was long lasting in lesioned mice but autoradiographic binding to high affinity 5-HT transporters was only transiently reduced. Male but not female lesioned mice reduced their exploration significantly in response to spatial rearrangement and object novelty, suggesting increased anxiety in response to change but normal spatial cognition. Our data show that developmental disruptions in the serotonergic innervation of cortex and hippocampus are sufficient to induce permanent, sex specific, behavioral alterations. These results may have significant implications for understanding brain disorders presenting with cortical morphogenetic abnormalities and altered serotonin neurotransmission, such as autism, schizophrenia and affective disorders.

show abstract

“…Additional evidence for 5-HT involvement in the development of neonatal rodent somatosensory cortex comes from the transient barrel-like distribution of 5-HT (Fujimiya et al, 1986;D'Amato et al, 1987;Rhoades et al, 1990;Blue et al, 1991;Bennett-Clarke et al, 1991, 1994aDori et al, 1996), of 5-HT 1B and 5-HT 2A receptors (Leslie et al, 1992;Bennett-Clarke et al, 1993;Mansour-Robaey et al, 1998), and of the 5-HT transporter (D'Amato et al, 1987; for review, see Fuchs, 1995;Lebrand et al, 1996;Mansour-Robaey et al, 1998). The transient barrel-like 5-HT pattern visualized in layer IV of the somatosensory cortex of neonatal rodents apparently stems from 5-HT uptake and vesicular storage in thalamocortical neurons, which surprisingly express both the plasma membrane serotonin transporter (5-HTT) and the vesicular monoamine transporter (VMAT2) at this developmental stage (Lebrand et al, 1996).…”

mentioning

confidence: 99%

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

et al. 2001

View full text Add to dashboard Cite

Thalamocortical neurons innervating the barrel cortex in neonatal rodents transiently store serotonin (5-HT) in synaptic vesicles by expressing the plasma membrane serotonin transporter (5-HTT) and the vesicular monoamine transporter (VMAT2). 5-HTT knock-out (ko) mice reveal a nearly complete absence of 5-HT in the cerebral cortex by immunohistochemistry, and of barrels, both at P7 and adulthood. Quantitative electron microscopy reveals that 5-HTT ko affects neither the density of synapses nor the length of synaptic contacts in layer IV. VMAT2 ko mice, completely lacking activity-dependent vesicular release of monoamines including 5-HT, also show a complete lack of 5-HT in the cortex but display largely normal barrel fields, despite sometimes markedly reduced postnatal growth. Transient 5-HTT expression is thus required for barrel pattern formation, whereas activity-dependent vesicular 5-HT release is not.

show abstract

Quantified distribution of serotonin transporter and receptors during the postnatal development of the rat barrel field cortex

Cited by 48 publications

References 22 publications

Modeling early cortical serotonergic deficits in autism

Modeling early cortical serotonergic deficits in autism

Neonatal serotonin depletion alters behavioral responses to spatial change and novelty

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

Contact Info

Product

Resources

About