Postsynaptic bursting is essential for ‘Hebbian’ induction of associative long-term potentiation at excitatory synapses in rat hippocampus

TLDR: Results indicate that, under the authors' conditions, postsynaptic bursting activity is necessary for associative synaptic potentiation at CA1 excitatory synapses in adult hippocampus, and is likely to have important implications for the understanding of cortical network operation.

Abstract: Associative long-term potentiation (LTP) is the dominant model of memory related synaptic modifications in the mammalian brain (Bliss & Lomo, 1973; Bliss & Collingridge, 1993). It has been studied mainly in the hippocampus, a structure of importance for memory (Morris et al. 1983; Squire & Zola-Morgan, 1991). Induction of associative LTP requires activation of the N-methyl-D-aspartate (NMDA) receptor (Collingridge et al. 1983; Bliss & Collingridge, 1993), which serves as a molecular coincidence detector, requiring both presynaptic release of glutamate and postsynaptic depolarization for its activation (Nowak et al. 1984; Mayer et al. 1984). Thus associative LTP obeys Hebb's learning rule (Hebb, 1949), which suggests that when the pre- and postsynaptic elements are active at the same time then the synapse between them will be strengthened. Indeed, pairing of presynaptic and postsynaptic activity can, under some experimental conditions, lead to synaptic potentiation (Wigstrom et al. 1986; Magee & Johnston, 1997; Markram et al. 1997). However, the physiological activity that occurs during learning behaviours and which produces the critical activation of NMDA receptors, leading to synaptic potentiation in adult hippocampus, has not been determined. According to a common interpretation of Hebb's learning rule, synaptic potentiation would be expected to occur following temporal coincidence of presynaptic activity and postsynaptic single action potentials. However, when a rat learns about spatial relations during active exploration of an environment, neurons with appropriate place fields, i.e. coding for the current location of the rat in space, and therefore those neurons that are likely to be involved in associative memories, typically show bursting activity repeated at theta frequency (5-12 Hz) (e.g. O'Keefe & Recce, 1993). Perhaps postsynaptic bursts bear a special significance for associative synaptic modification. We wanted to test directly the common interpretation of Hebb's rule, by investigating whether coincident single pre- and postsynaptic action potentials are sufficient to induce LTP in hippocampal slices from adult rat. In order to investigate whether bursts have a special role in associative synaptic modification, we compared the efficacy of pairing pre- and postsynaptic single action potentials and pre- and postsynaptic bursts in inducing synaptic change using neuronal activity seen during exploratory learning.