Relations Between Long‐term Synaptic Modifications and Paired‐pulse Interactions in the Rat Neocortex

Abstract

The phenomenon of paired-pulse facilitation (PPF) was exploited to investigate the role of presynaptic mechanisms in the induction and maintenance of long-term synaptic plasticity in the neocortex. Long-term potentiation (LTP) and depression (LTD) were induced without afferent activation by applying tetani of intracellular pulses. Our results show that synaptic modifications closely resembling LTP and LTD can be induced by postsynaptic activation alone. The polarity of these synaptic modifications depends on initial properties of the input, as indicated by a correlation between initial PPF ratio and post-tetanic amplitude changes: inputs exhibiting strong PPF, which might be associated with low release probability tend to be potentiated, while inputs with small PPF are more likely to show depression. Maintenance of both LTP and LTD involve presynaptic mechanisms, as indicated by changes in PPF ratios and in failure rate after LTP or LTD induction. Presynaptic mechanisms could include changes in release probability and/or in the number of active release sites. Because induction was postsynaptic, this supports the notion of a retrograde signal. The relative contribution of pre- and postsynaptic mechanisms in the maintenance of long-term synaptic modifications depends on the initial state of the synaptic input and on LTP magnitude. PPF changes were especially pronounced in inputs which had initially high PPF and underwent strong potentiation. Since LTP and LTD are associated with changes of PPF ratios these synaptic modifications do not only alter the gain but also the temporal properties of synaptic transmission. Because of the LTP associated reduction of PPF, potentiated inputs profit less from temporal summation, favouring transmission of synchronized, low frequency activity.

Neocortical Long-Term Potentiation and Long-Term Depression: Site of Expression Investigated by Infrared-Guided Laser Stimulation

“…This has been shown directly by Malgaroli et al (1995), who reported enhanced synaptic vesicle cycling during hippocampal LTP, and recently by Zakharenko et al (2001). Such an effect can be caused by an increased release probability, which has been described for neocortical synapses (Volgushev et al, 1997). Alternatively, an enhancement of presynaptic neuronal excitability by correlated presynaptic and postsynaptic activity (Ganguly et al, 2000) is also conceivable.…”

Phase Sensitivity of Synaptic Modifications in Oscillating Cells of Rat Visual Cortex

“…Thus, in older rats, synaptic modifications were no longer phase sensitive and consisted exclusively of LTD. Both LTP and LTD can be induced in the absence of presynaptic stimulation if the postsynaptic neuron is strongly activated by current injection (Alonso et al, 1990;Volgushev et al, 1997) or antidromic stimulation (Christofi et al, 1993). To test whether nonassociative mechanisms had contributed to LTD induction, we performed six experiments in P22 slices, with postsynaptic suprathreshold 20 Hz V m oscillations, but without evoking EPSPs.…”

Interaction between intracellular tetanization and pairing-induced long-term synaptic plasticity in the rat visual cortex

“…First, the mutual interaction between the pairing procedure and a purely postsynaptic challenge, intracellular tetanization, suggests that intracellular cascades which mediate plastic changes induced by the two protocols have common elements. Second, the dependence of synaptic changes on the preceding stimulation indicates that a plasticity-inducing challenge not only modifies the synaptic gain, but also shifts the balance between the potentiation and depression mechanisms, thus modulating the predispositions of the inputs to undergo potentiation or depression 20 and influencing the direction of the future changes. 1 …”

“…20 The rats were anaesthetized with ether and decapitated, and slices of the visual cortex were prepared in an ice-cold perfusion medium containing (in mM): 125 NaCl, 2.5 KCl, 1.5 MgSO 4 , 2 CaCl 2 , 1.25 Na 2 HPO 4 , 25 NaHCO 3 and 25 d-glucose (pH 7.4), and bubbled with 95% O 2 /5% CO 2 . Intracellular recordings from layer 2/3 pyramidal cells were obtained with sharp microelectrodes (2.5 M potassium acetate or 1.2 M potassium acetate with 1% biocytin) under submerged conditions at 30ЊC.…”

“…No synaptic stimuli were applied during intracellular tetanization. The intracellular tetanization can be considered as a purely postsynaptic challenge, 19,20 because spiking of a single layer 2/3 pyramidal cell cannot lead to generation of action potentials in other cells and thus cannot activate polysynaptic pathways. 18 Autaptic synapses are unlikely to contribute substantially to our test responses.…”