Neurotransmitter release at the thalamocortical synapse instructs barrel formation but not axon patterning in the somatosensory cortex.

To assess the impact of synaptic neurotransmitter release on neural circuit development, we analyzed barrel cortex formation after thalamic or cortical ablation of RIM1 and RIM2 proteins, which control synaptic vesicle fusion. Thalamus-specific deletion of RIMs reduced neurotransmission efficacy by 67%. A barrelless phenotype was found with a dissociation of effects on the presynaptic and postsynaptic cellular elements of the barrel. Presynaptically, thalamocortical axons formed a normal whisker map, whereas postsynaptically the cytoarchitecture of layer IV neurons was altered as spiny stellate neurons were evenly distributed and their dendritic trees were symmetric. Strikingly, cortex-specific deletion of the RIM genes did not modify barrel development. Adult mice with thalamic-specific RIM deletion showed a lack of activity-triggered immediate early gene expression and altered sensory-related behaviors. Thus, efficient synaptic release is required at thalamocortical but not at corticocortical synapses for building the whisker to barrel map and for efficient sensory function.

Early development of the thalamic inhibitory feedback loop in the primary somatosensory system of the newborn mice.

Spontaneous neuronal activity plays an important role during the final development of the brain circuits and the formation of the primary sensory maps. In young rats, spindle bursts have been recorded in the primary somatosensory cortex. They are correlated with spontaneous muscle twitches and occur before active whisking. They bear similarities with the spindles recorded in adult brain that occur during early stages of sleep and rely on a thalamic feedback loop between the glutamatergic nucleus ventroposterior medialis (nVPM) and the GABAergic nucleus reticularis thalami (nRT). However, whether a functional nVPM-nRT loop exists in newborn rodents is unknown. We studied the reciprocal synaptic connections between nVPM and nRT in thalamic acute slices from mice from birth [postnatal day 0 (P0)] until P9. We first demonstrated that nVPM-to-nRT EPSCs could be distinguished from corticothalamic EPSCs by their inhibition by 5-HT attributable to the transient expression of functional presynaptic serotonin 1B receptors. The nVPM-to-nRT EPSCs and nRT-to-nVPM IPSCs were both detected the first day after birth; their amplitude near 2 nS was relatively stable until P5. At P6-P7, there was a rapid and simultaneous increase of both nVPM-to-nRT EPSCs and nRT-to-nVPM IPSCs that reached 8 and 9 nS, respectively. Our results show that the thalamic synapses implicated in spindle activity are functional shortly after birth, suggesting that they could already generate spindles during the first postnatal week. Our results also suggest an inhibitory action of 5-HT on the spindle bursts of the newborn mice.

Activity-dependent presynaptic effect of serotonin 1B receptors on the somatosensory thalamocortical transmission in neonatal mice.

The disruptive effect of excessive serotonin (5-HT) levels on the development of cortical sensory maps is mediated by 5-HT1B receptors, as shown in barrelless monoamine oxidase A knock-out mice, in which the additional inactivation of 5-HT1B receptors restores the barrels. However, it is unclear whether 5-HT1B receptors mediate their effect on barrel formation by a trophic action or an activity-dependent effect. To test for a possible effect of 5-HT1B receptors on activity, we studied the influence of 5-HT on the thalamocortical (TC) synaptic transmission in layer IV cortical neurons. In TC slices of postnatal day 5 (P5)-P9 neonate mice, we show that 5-HT reduces monosynaptic TC EPSCs evoked by low-frequency internal capsule stimulation and relieves the short-term depression of the EPSC evoked by high-frequency stimulation. We provide evidence that 5-HT decreases the presynaptic release of glutamate: 5-HT reduces similarly the AMPA-kainate and NMDA components and the paired pulse depression of TC EPSCs. We show also that 5-HT1B receptors mediate exclusively the effect of 5-HT: first, the effect of 5-HT on the TC EPSC is correlated with the transient expression of 5-HT1B receptor mRNAs in the ventrobasal thalamic nucleus during postnatal development; second, it is mimicked by a 5-HT1B agonist; third, 5-HT has no effect in 5-HT1B receptor knock-out mice. Our results show that in the developing barrel field of the neonatal mice, 5-HT1B receptors mediate an activity-dependent regulation of the TC EPSC that could favor the propagation of high-frequency TC activity.