Silent synapses in the developing hippocampus: Lack of functional AMPA receptors or low probability of glutamate release?

Abstract

At early developmental stages, silent synapses have been commonly found in different brain areas. These synapses are called silent because they do not respond at rest but are functional at positive membrane potentials. A widely accepted interpretation is that N-methyl-D-aspartate (NMDA) but not ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are functionally expressed on the subsynaptic membrane. Here we show that, in both CA3 and CA1 hippocampal regions, AMPA-mediated synaptic responses can be detected already at early stages of postnatal development. However, some synapses appear silent because of a very low probability of glutamate release. They can be converted into functional ones by factors that enhance release probability such as paired-pulse stimulation, increasing the temperature or cyclothiazide (CTZ), a drug that blocks AMPA receptor desensitization and increases transmitter release. Conversely, conducting synapses can be switched off by increasing the frequency of stimulation. Although we cannot exclude that ''latent AMPA receptors'' can become functional after activity-dependent processes, our results clearly indicate that, in the neonatal hippocampus, a proportion of glutamatergic synaptic connections are presynaptically rather than postsynaptically silent.

GABA-mediated giant depolarizing potentials as coincidence detectors for enhancing synaptic efficacy in the developing hippocampus

“…It is also possible that the initial pairing-induced increase in intracellular calcium trigger coordinated pre-and postsynaptic modifications, thus promoting the cross talk between pre and postsynaptic elements. Whatever the mechanisms, GDPs appear to be effective in ''unsilencing'' silent connections and for strengthening those with low probability of transmitter release (23,(28)(29). They might also be instructive in promoting synapse development in those neurons ''silent'' because of the lack of presynaptic specialization (48).…”

“…Experiments were performed on hippocampal slices obtained from postnatal day 1 (P1)-P6 Wistar rats as described (23). Briefly, animals were decapitated after being anaesthetized with an i.p.…”

Cholinergic Modulation of Appetite-Related Synapses in Mouse Lateral Hypothalamic Slice

“…Long delays after tetanic stimulation is also reminiscent of "silent synapses," a phenomenon attributed to both presynaptic and postsynaptic plasticity (Liao et al, 1995;Malenka and Nicoll, 1997;Gasparini et al, 2000). Our slices were routinely from P14 -P17 mice, and the cholinergic projections, although present, may be immature.…”

Invited Review: Neuroplasticity in respiratory motor control

“…In some neural systems, nonfunctional synaptic pathways exist. These existing but ineffective synaptic pathways can be enhanced by experimental manipulations or injury (48,71,128,129,190,247). In respiratory motor control, ineffective crossed spinal synaptic pathways to phrenic motoneurons are revealed by serotonin receptor activation (130,248), spinal injury (74,86,181), and spinal sensory denervation (63).…”