Developmental remodelling of the lemniscal synapse in the ventral basal thalamus of the mouse

Abstract

Synapse elimination occurs throughout the nervous system during development, and is essential for the formation of neural circuits. The mechanisms underlying synapse elimination in the brain, however, remain largely unknown. Using whole-cell patch-clamp recording in a slice preparation, we examined synaptic refinement at the somatosensory relay synapse (lemniscal synapse) in the ventral basal thalamus of the mouse during postnatal development. At 1 week old, each neuron in the ventral basal thalamus is innervated by multiple lemniscal fibres, as revealed by multiple increments of the synaptic response. By 16 days after birth (P16), the majority of neurons showed an all-or-none response, suggesting a single fibre innervation. In addition to synapse elimination, extensive modifications in synaptic properties occur during the second week after birth. The ratio of AMPA to NMDA component of the synaptic current tripled between P7 and P17. The decay constant of the NMDA component decreased by about 70% between P7 and P17; ifenprodil (3 μM) reduced the NMDA component by about 40% in neurons at P7-9, but was much less effective at P20-24. On the other hand, there was little change in the inward rectification of AMPA component between P11 and P24. Paired-pulse ratios, measured at −70 and +40 mV, were stable between P7 and P24. Whisker deprivation from P5 through P19 had no effect on the elimination or the maturation of the lemniscal synapse. These results suggest that the lemniscal synapse in the ventral basal thalamus undergoes extensive refinement during the second week, and that sensory experience has a rather limited role in this process.

Essential role of postsynaptic NMDA receptors in developmental refinement of excitatory synapses

“…At P7, all VPm neurons in SERT-Grin1 −/− mice showed NMDAR-and AMPAR-EPSCs (14 of 14 cells from two mice; Fig. 1 from C57BL6 (B6) mice at the same age (5). At P10, however, 50% of VPm neurons (12 of 24 cells from three mice) showed only AMPAR-EPSCs, with very small or no NMDAR-EPSCs (Fig.…”

“…As in many other brain areas, the maturation of vibrissal relay synapses is marked by a rapid increase in the amplitude of AMPAR-EPSCs (5,30,32). To determine the role of NMDARs in synaptic maturation, we analyzed AMPAR-EPSCs in SERT-Grin1 −/− mice.…”

“…Tactile information from vibrissa is relayed to neurons in ventral posteromedial nucleus (VPm) of the thalamus by ascending axons from the principal trigeminal nucleus (Pr5) in the brainstem. VPm relay synapses undergo extensive refinement during the second week after birth (5). At postnatal day (P) 7, each VPm neuron is contacted by approximately six ascending axons from the brainstem; by P14, the majority of neurons receive a single ascending axon (30).…”

“…D uring early development in vertebrates, neurons in many parts of the nervous system form weak synapses with a large number of target cells (1)(2)(3)(4)(5)(6)(7). This early pattern of connectivity is refined through two processes: synapse elimination that removes many initial connections and synapse maturation whereby the remaining connections are strengthened (8,9).…”

Signal processing in the tectothalamic pathway.

“…The amplitudes of EPSPs elicited by stimulation of layer VI corticothalamic inputs (RS profiles) remain stable at low stimulation frequencies «1 Hz), but facilitate with increasing stimulation frequency (Lindstrom and Wrobel, 1990;Turner and Salt, 1998;von Krosigk et aI., 1999;Granseth et aI., 2002). In contrast, the amplitudes of EPSPs generated by stimulation of ascending sensory inputs, or inputs that originate from cortical layer V (RL profiles), decrease in amplitude as the stimulation frequency is increased (Scharfman et aI., 1990;Ramoa and McCormick, 1994;Kao and Coulter, 1997;Turner and Salt, 1998;Chen and Regehr, 2000;Chen et aI., 2002;Li et aI., 2003b;Arsenault and Zhang, 2006). Finally, the amplitudes of EPSPs elicited by stimulation of tectothalamic inputs (RM profiles) remain relatively stable at stimulation frequencies up to 10 Hz.…”