Silent Synapses in the Immature Visual Cortex: Layer-Specific Developmental Regulation

Abstract

Central glutamatergic synapses are thought to initially form as immature, so-called silent synapses showing exclusively N-methyl-d-aspartate receptor-mediated synaptic transmission. Postsynaptic insertion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors during further development leads to a conversion into functional, mature synapses. Here, we tested the hypothesis that, according to the "inside first-outside last" pattern of neocortical layer formation and synaptogenesis, pyramidal cells in the superficial layers might show a higher fraction of silent synapses compared with pyramidal cells in the deep layers. We performed an electrophysiological analysis of glutamatergic synapses in acute rat visual cortex slices during postnatal development. In layer VI pyramidal neurons the incidence of silent synapses was high during the first postnatal week and strongly declined during further development. Surprisingly, in superficial cortical plate pyramidal neurons (immature layers II/III), the fraction of silent synapses was initially very low and increased up to the second postnatal week. Thereafter, a similar decline as found in layer VI pyramidal neurons was observed. Thus the developmental regulation of silent synapses was clearly different in pyramidal neurons from different neocortical layers. The almost complete absence of silent synapses at early stages in layer II/III pyramidal neurons indicates that an initially formed subset of synapses is constitutively functional. This might be important to enable spontaneous activity and latter activity-dependent maturation of synapses.

The Role of Nitric Oxide and GluR1 in Presynaptic and Postsynaptic Components of Neocortical Potentiation

“…for example, to unsilencing silent synapses would be unlikely at the ages we studied (6 -13 weeks) because silent synapses decrease to very low levels in layer II/III neurons even at 4 weeks of age (Rumpel et al, 2004). In support of this, we found no evidence of silent synapses in this pathway at this age in either GluR1 or wild-type mice (Fig.…”

“…First, studying adults made it extremely unlikely that we were observing a reduction in failures during LTP attributable to unsilencing silent synapses. Silent synapses are at high levels during development (Isaac et al, 1997) but are practically absent in layer II/III cortical cells beyond 4 weeks of age (Rumpel et al, 2004). The youngest animals in our studies were 6 weeks of age, with the majority being older than 8 weeks.…”

“…Plasticity mechanisms vary at different synapses (Nicoll and Malenka, 1995;Buonomano, 1999;Allen et al, 2000) and at different stages of development (Yasuda et al, 2003;Rumpel et al, 2004). Synaptic plasticity has perhaps been studied most extensively at the hippocampal Schaeffer collateral-CA1 synapse and, because of cell culture techniques and recording methods, more usually during development than in adulthood.…”

“…The major input pathways to layer II/III cells arise from layer IV cells (Feldmeyer et al, 2002), and this pathway has been implicated in plasticity in vivo (Glazewski et al, 1996;Finnerty et al, 1999;Feldman, 2000;Takahashi et al, 2003). We therefore studied plasticity in this pathway in adult animals (age 6 -13 weeks) to avoid developmental plasticity mechanisms such as silent synapses, which tend not to be present beyond 4 weeks in layers II/III of the cortex (Rumpel et al, 2004).…”

Differential Signaling to Subplate Neurons by Spatially Specific Silent Synapses in Developing Auditory Cortex

“…However, if a cell is depolarized, these synapses can become functionally active and potentially signal information. In the cerebral cortex, the majority of silent synapses mature along with cortical layers (Rumpel et al, 2004). Silent synapses generally decrease during development, but transient increases occur (Rumpel et al, 2004).…”