The development of synaptic transmission is time-locked to early social behaviors in rats (original) (raw)
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2020
The serotonin transporter (SERT) gene, especially the short allele of the human serotonin transporter linked polymorphic region (5-HTTLPR), has been associated with the development of stress-related neuropsychiatric disorders. In line, exposure to early life stress in SERT knockout animals contributes to anxiety- and depression-like behavior. However, there is a lack of investigation of how early-life exposure to beneficial stimuli, such as tactile stimulation (TS), affects later life behavior in these animals. In this study, we investigated the effect of TS on social, anxiety, and anhedonic behavior in heterozygous SERT knockouts rats and wild-type controls and its impact on gene expression in the basolateral amygdala. Heterozygous SERT+/– rats were submitted to TS during postnatal days 8–14, for 10 min per day. In adulthood, rats were assessed for social and affective behavior. Besides, brain-derived neurotrophic factor (Bdnf) gene expression and its isoforms, components of glutam...
Anatomical record (Hoboken, N.J. : 2007), 2011
In rodents, noradrenergic (NE) locus coeruleus (LC) neurons are well known to express tyrosine hydroxylase (TH) immunoreactivity. However, due to its very low enzyme activity, NE cortical fibers do not typically express TH immunoreactivity, thus dopamine-β-hydroxylase (DBH) immunoreactivity is commonly utilized as a marker for NE cortical fibers. In this study, we performed double and/or triple immunofluorescent staining using antibodies against TH, DBH, and/or norepinephrine transporter (NET) to investigate the altered NE TH expression of cortical fibers in citalopram (CTM)-exposed rats and monoamine oxidase (MAO) A knock out (KO) mice. We have noted the following novel findings: (1) neonatal exposure to the selective serotonin reuptake inhibitor (SSRI) CTM enhanced NE TH immunoreactive fibers throughout the entire neocortex, and a few of them appeared to be hypertrophic; (2) slightly enhanced NE cortical TH immunoreactive fibers were also noted in MAO A KO mice, and many of them revealed varicosities compared with the rather smooth NE cortical TH immunoreactive fibers in wild-type (WT) mice; (3) LC dendrites of MAO A KO mice exhibited beaded morphology compared with the smooth LC dendrites in WT mice. Our findings suggest that both genetic and environmental factors during early development may play a critical role in the regulation and proper function of NE TH expression in the neocortex.
Neonatal serotonin depletion affects developing and mature mouse cortical neurons
NeuroReport, 2000
for critically reviewing the manuscript, and to Dr J.M. Fritschy for the gift of the á1 and á5 GABA A receptor subunits. This work is presented by J.D. in part of the ful®llment of its medical doctoral degree at the University of Lausanne. This research was supported by the SNF grant 31-40852.94 and 31-50565.97. The early expression of neurotransmitters and receptors in the developing brain has brought attention to their potential contribution in modulating neuronal developmental processes. Monoamines are among the ®rst neurotransmitter systems to develop during embryogenesis. Depletion of neocortical serotonin or catecholamine afferents with selective neurotoxins resulted in a permanent alteration of the dendritic arborization of calretinin-containing interneurons, and a transient delay of parvalbumin and calbindin expression in a number of cortical neurones during the second postnatal week. The expression pattern of other developmentally regulated proteins, such as two subunits of the GABA A receptor, was not altered. Depletion of serotonin, and in part catecholamines, appeared to perturb several developmental processes of the cerebral cortex which would interfere with both its maturation and adult circuitry. NeuroReport 11:833±837 & 2000 Lippincott
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010
Environmental stimulation is critical for brain development. Here, we report that natural stimulation through enriched environment (EE) rearing during the first 2 weeks of mouse postnatal development promotes GABAergic neurotransmission and accelerates maturation of GABAergic and glutamatergic synapses. Using whole-cell recordings from CA1 pyramidal neurons in acute hippocampal slices, we found that EE-reared mice exhibited higher amplitude of miniature GABAergic postsynaptic currents (mGPSCs) at 1 week of postnatal development, as well as accelerated transition of GABA action from excitation to inhibition, compared with mice reared under standard housing conditions. This enhanced GABAergic synaptic transmission persisted until the end of the second postnatal week, when GABA mostly acts as an inhibitory neurotransmitter. Consistent with these electrophysiological results, we observed elevated levels of GABA A receptors and the K ϩ -Cl Ϫ cotransporter KCC2. Similarly, increased levels of excitatory synaptic components, including NMDA and AMPA receptors and the scaffolding protein PSD95, were detected in synaptosomal fractions from the forebrain/hippocampus of EEreared mice during the first two postnatal weeks. Functional increase in glutamatergic synaptic transmission, as measured by increased amplitude of miniature and spontaneous EPSCs, was also detected during the second postnatal week. Together, these results demonstrate that early environmental stimulation through EE rearing enhances early postnatal GABAergic neurotransmission, which is known to play important trophic functions in many aspects of neural development.
Molecular Psychiatry, 2020
Serotonin and dopamine are associated with multiple psychiatric disorders. How they interact during development to affect subsequent behavior remains unknown. Knockout of the serotonin transporter or postnatal blockade with selective-serotonin-reuptake inhibitors (SSRIs) leads to novelty-induced exploration deficits in adulthood, potentially involving the dopamine system. Here we show in the mouse that raphe nucleus serotonin neurons activate ventral tegmental area dopamine neurons via glutamate co-transmission and that this co-transmission is reduced in animals exposed postnatally to SSRIs. Blocking serotonin neuron glutamate co-transmission mimics this SSRI-induced hypolocomotion, while optogenetic activation of dopamine neurons reverses this hypolocomotor phenotype. Our data demonstrate that serotonin neurons modulate dopamine neuron activity via glutamate co-transmission and that this pathway is developmentally malleable, with high serotonin levels during early life reducing co-transmission, revealing the basis for the reduced novelty-induced exploration in adulthood due to postnatal SSRI exposure. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
European Journal of Neuroscience, 2012
The developing brain is not a small adult brain. Voltage‐ and transmitter‐gated currents, like network‐driven patterns, follow a developmental sequence. Studies initially performed in cortical structures and subsequently in subcortical structures have unravelled a developmental sequence of events in which intrinsic voltage‐gated calcium currents are followed by nonsynaptic calcium plateaux and synapse‐driven giant depolarising potentials, orchestrated by depolarizing actions of GABA and long‐lasting NMDA receptor‐mediated currents. The function of these early patterns is to enable heterogeneous neurons to fire and wire together rather than to code specific modalities. However, at some stage, behaviourally relevant activities must replace these immature patterns, implying the presence of programmed stop signals. Here, we show that the developing striatum follows a developmental sequence in which immature patterns are silenced precisely when the pup starts locomotion. This is mediated...
Denial of Reward in the Neonate Shapes Sociability and Serotonergic Activity in the Adult Rat
2013
Background: Manipulations of the early environment are linked to long-lasting alterations of emotionality and social capabilities. Denial of rewarding mother-pup interactions in early life of rats could serve as model for child neglect. Negative consequences for social competence in later life, accompanied by changes in the serotonergic system would be expected. In contrast, rewarding mother-pup contact should promote adequate social abilities. Methodology/Principal Findings: Male Wistar rats trained in a T-maze during postnatal days 10–13 under denial (DER) or permission (RER) of maternal contact were tested for play behavior in adolescence and for coping with defeat in adulthood. We estimated serotonin (5-HT) levels in the brain under basal conditions and following defeat, as well as serotonin receptor 1A (5-HT1A) and serotonin transporter (SERT) expression. DER rats exhibited increased aggressive-like play behavior in adolescence (i.e. increased nape attacks, p,0.0001) and select...
Psychopharmacology, 2007
Rationale Serotonin is an important modulator of social behaviour. Individual differences in serotonergic signalling are considered to be a marker of personality that is stable throughout lifetime. While a large body of evidence indicates that central serotonin levels are inversely related to aggression and sexual behaviour in adult rats, the relationship between serotonin and social behaviour during peri-adolescence has hardly been explored. Objective To study the effect of acute and constitutive increases in serotonin neurotransmission on social behaviour in peri-adolescent rats. Materials and methods Social behaviour in peri-adolesent rats (28-35 days old) was studied after genetic ablation of the serotonin transporter, causing constitutively increased extra-neuronal serotonin levels, and after acute treatment with the serotonin reuptake inhibitor fluoxetine or the serotonin releasing agent 3,4-methylenedioxymethamphetamine (MDMA). A distinction was made between social play behaviour that mainly occurs during peri-adolescence, and non-playful social interactions that are abundant during the entire lifespan of rats.
Development of Serotonergic Fibers in the Post-Natal Mouse Brain
Frontiers in Cellular Neuroscience, 2017
Serotonin (5-HT)-synthetizing neurons, which are confined in the raphe nuclei of the rhombencephalon, provide a pervasive innervation of the central nervous system (CNS) and are involved in the modulation of a plethora of functions in both developing and adult brain. Classical studies have described the post-natal development of serotonergic axons as a linear process of terminal field innervation. However, technical limitations have hampered a fine morphological characterization. With the advent of genetic mouse models, the possibility to label specific neuronal populations allowed the rigorous measurement of their axonal morphological features as well as their developmental dynamics. Here, we used the Tph2 GFP knock-in mouse line, in which GFP expression allows punctual identification of serotonergic neurons and axons, for confocal microscope imaging and we performed 3-dimensional reconstruction in order to morphologically characterize the development of serotonergic fibers in specified brain targets from birth to adulthood. Our analysis highlighted region-specific developmental patterns of serotonergic fiber density ranging from a linear and progressive colonization of the target (Caudate/Putamen, Basolateral Amygdala, Geniculate Nucleus and Substantia Nigra) to a transient increase in fiber density (medial Prefrontal Cortex, Globus Pallidus, Somatosensory Cortex and Hippocampus) occurring with a regionspecific timing. Despite a common pattern of early post-natal morphological maturation in which a progressive rearrangement from a dot-shaped to a regular and smooth fiber morphology was observed, starting from post-natal day 28 serotonergic fibers acquire the region specific morphological features present in the adult. In conclusion, we provided novel, target-specific insights on the morphology and temporal dynamics of the developing serotonergic fibers.
Serotonin modulates excitatory synapse maturation in the developing prefrontal cortex
Nature communications, 2024
Serotonin (5-HT) imbalances in the developing prefrontal cortex (PFC) are linked to long-term behavioral deficits. However, the synaptic mechanisms underlying 5-HT-mediated PFC development are unknown. We found that chemogenetic suppression and enhancement of 5-HT release in the PFC during the first two postnatal weeks decreased and increased the density and strength of excitatory spine synapses, respectively, on prefrontal layer 2/3 pyramidal neurons in mice. 5-HT release on single spines induced structural and functional long-term potentiation (LTP), requiring both 5-HT2A and 5-HT7 receptor signals, in a glutamatergic activity-independent manner. Notably, LTPinducing 5-HT stimuli increased the long-term survival of newly formed spines (≥ 6 h) via 5-HT7 Gα s activation. Chronic treatment of mice with fluoxetine, a selective serotonin-reuptake inhibitor, during the first two weeks, but not the third week of postnatal development, increased the density and strength of excitatory synapses. The effect of fluoxetine on PFC synaptic alterations in vivo was abolished by 5-HT2A and 5-HT7 receptor antagonists. Our data describe a molecular basis of 5-HT-dependent excitatory synaptic plasticity at the level of single spines in the PFC during early postnatal development. Brain development requires a precise interplay of neurochemicals that mediate neuronal communication and circuit formation 1,2. 5-HT is one of the earliest detected neuromodulators 3 with cortical levels peaking within two years after birth in humans and the first postnatal week in rodents 4,5. Changes in gestational and early postnatal 5-HT levels can arise from many causes including maternal deprivation or abuse, diets high or low in tryptophan, or the use of medications such as selective serotonin reuptake inhibitors (SSRIs) that can readily cross the placenta or be passed to offspring through breast feeding 5-8. Disbalances of 5-HT during brain development are associated with increased risk of neurodevelopmental disorders such as autism spectrum disorder and long-lasting behavioral deficits 7,9-13 , but the underlying mechanisms remain elusive. The PFC is a brain region which plays a critical role in higher-order cognition such as social aptitude and cognitive flexibility 14. Serotonergic (5-HTergic) axons originating from the raphe nuclei in the brainstem densely innervate the PFC and modulate its function 15. Altered 5-HTergic signaling is thus strongly implicated in many of the PFC-dependent behavioral changes observed in neurodevelopmental disorders 7,10,12,13 , and enhanced 5-HT levels in the PFC via early exposure to SSRIs are associated with behavioral impairments that last into adulthood 9,11. While there is a clear link between 5-HTergic signaling and cognitive development, the cellular and synaptic mechanisms of 5-HT actions on neuronal plasticity and how they are altered by 5-HT imbalance in the developing PFC remain poorly understood. Maturation and stabilization of excitatory synapses set the foundation for neural circuit formation 16-19. Dendritic spines, the primary postsynaptic sites for excitatory synapses, form and mature to support functional circuits through activity-dependent synaptic mechanisms 20. High levels of 5-HT in early brain development coincide with the critical period of experience-dependent excitatory synapse maturation 21. Consistently, prior studies have implicated 5-HTergic signaling in