Reversible synaptic depression in developing rat CA3-CA1 synapses explained by a novel cycle of AMPA silencing-unsilencing

• In the developing hippocampus, experiments using whole cell recordings have shown that a small number of synaptic activations can convert many glutamate synapses to AMPA silent synapses. This depression of AMPA signaling is induced by low-frequency (0.05–0.2 Hz) activation, does not require N-methyl-d-aspartate or metabotropic glutamate receptor activation for its induction, and does not readily reverse after stimulus interruption. Here we show, using field recordings and perforated patch-clamp recordings of transmission in developing CA3–CA1 synapses, that this synaptic depression also can be observed under more noninvasive recording conditions. Moreover, under these conditions, the synaptic depression spontaneously recovers within 20 min by the absence of synaptic activation alone, with a time constant of ∼7 min as determined by field excitatory postsynaptic potential recordings. Thus as for the expression of long-term potentiation (LTP), recovery from this depression is susceptible to whole cell dialysis (“wash-out”). In contrast to LTP-induced unsilencing, the AMPA signaling after stimulus interruption was again labile, resumed stimulation resulted in renewed depression. The present study has thus identified a novel cycle for AMPA signaling in which the nascent glutamate synapse cycles between an AMPA silent state, induced by a small number of synaptic activations, and a labile AMPA signaling, induced by prolonged inactivity.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

long-term potentiation

developing hippocampus

receptor trafficking

excitatory synapses

plasticity

proteins

psd-95

activation

expression

induction

Publication and Content Type

ref (subject category)

art (subject category)