Gustafsson, B. | Search bioRxiv

bioRxiv2024

Hebbian induction adds AMPA-labile signaling units to CA3-CA1 synapses in the developing hippocampus

In the 2nd postnatal week hippocampus, Hebbian-induced long-term potentiation (LTP) of AMPA receptor-mediated transmission in CA3-CA1 synapses is not a genuine potentiation. Instead, it is a de-depression (unsilencing) and temporary stabilization of postsynaptically AMPA-labile synapses silenced by a prior test pulse (0.03 - 0.2 Hz) stimulation. In addition to such an LTP, Hebbian induction at these synapses also results in a labile potentiation that becomes depotentiated by test pulse stimulation, thus appearing as an Hebbian-induced short- term potentiation (STP). Although the induction of this labile potentiation was blocked in the combined presence of N-methyl-D-aspartate (NMDA) and metabotropic glutamate (mGlu) receptor antagonists, the depotentiation was not affected by these drugs. The labile potentiation was not associated with a change in paired-pulse ratio and was, after a depotentiation, fully re-established by a 20 min interruption of test pulse stimulation. These properties are shared with the silencing of previously non-stimulated (naive) AMPA-labile synapses by such test pulse stimulation. However, the depotentiation following an Hebbian induction is not a re-silencing of naive AMPA labile synapses since there is no correlation between the magnitudes of depotentiation and preceding silencing of naive synapses. The present results suggest that Hebbian induction at these neonatal CA3-CA1 synapses, in addition to unsilencing and temporary stabilization of AMPA-labile transmission, creates a labile potentiation based on the insertion/activation of an additional AMPA-labile signaling unit to a pre-existing synapse.

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bioRxiv2024

Hebbian activity only temporarily stabilizes synaptic transmission at CA3 - CA1 synapses in the developing hippocampus

Prolonged low frequency (0.05-1 Hz) stimulation of previously non-stimulated (naive) CA3-CA1 synapses in the developing hippocampus results in a profound synaptic depression explained by a postsynaptic AMPA silencing. It has been proposed that Hebbian activity can stabilize the synapses by preventing such depression. Using field recordings, we have examined to which extent strong repeated high frequency tetanization simulating Hebbian activity results in such prevention. The tetanization resulted within minutes in a field EPSP potentiation to 150-170% of the naive field EPSP level which remained unaltered if stimulation was suspended. If test pulse stimulation (0.2 Hz) was allowed to continue after the tetanization the field EPSP continuously decreased and was after 2700 stimuli depressed by 75% from the potentiated level. This depression did not differ in relative terms from that induced in naive synapses (by 82% from the naive level). The long-lasting component of this depression revealed by a subsequent 30 min stimulus interruption (by 59% from the potentiated level) did not differ from that of naive synapses (by 66% from the naive level). This equal relative degree of depression of tetanized and naive synapses was also observed following 2700 stimuli at 1 Hz. On the other hand, when examined at earlier time points during the test pulse stimulation (e.g. after 400-900 stimuli) tetanized synapses were less depressed than naive synapses, and the long-lasting depression after 900 stimuli at 1 Hz was only half that observed in naive synapses. This effect of tetanization was observed independently of whether the 1 Hz stimulation was commenced 15 min or 2 hours after the tetanization. In conclusion, while a strong preceding tetanization results in a partial stabilization of transmission at CA3-CA1 synapses in the developing hippocampus, this effect appears only temporary. This temporary effect is not linked to time after tetanization but to the number of low frequency stimuli given.

neuroscience↗