Developmental regulation of synaptic function of the hippocampal glutamatergic synapse

Abstract

The mature mammalian brain and spinal cord contain billions of neurons which are interconnected by means of synapses. The most prevalent type of synapse is excitatory, using the amino acid glutamate as transmitter. The aim of this study was to acquire knowledge of basic synaptic properties at recently formed glutamatergic hippocampal synapses, to help understand how the development of a fully functional mature brain is accomplished. The study was performed in vitro, using slices of hippocampus from rats. Excitatory synaptic transmission between Schaffer collaterals / commissural fibers and pyramidal cells in the hippocampal CA1 region was investigated using standard extra- and intracellular recording techniques.It was shown that some functional properties of the early postnatal synapses differ from properties at more mature synapses. The results can be summarized as follows; i) there is a developmental switch in release properties during the second postnatal week, leading to a lower release probability. However, this change seems to occur only at a small group of synapses with initial high release probability. ii) For the early postnatal synapse, but not for the mature one, low frequency afferent activation could lead to a rapid and total silencing of AMPA receptor-mediated signaling, a previously unrecognized form of synaptic plasticity. Synapses may thus not be formed without functional AMPA receptor-mediated transmission (AMPA-silent), as commonly believed, but with both functional AMPA and NMDA receptors. iii) The early postnatal synapse shows a heightened susceptibility to long-term depression. This developmental form of LTD appears to differ from the more mature form regarding triggering mechanism, synapse specificity, and possibly site of expression. Conclusion: The findings of this study show that synapses during the early postnatal period differ both in release properties and in synaptic plasticity mechanisms, when compared to synapses at around the onset of puberty. It is proposed that the properties of synapses during early development are important for a correct neural circuitry to evolve.