A Synaptically Controlled, Associative Signal for Hebbian Plasticity in Hippocampal Neurons

Abstract

The role of back-propagating dendritic action potentials in the induction of long-term potentiation (LTP) was investigated in CA1 neurons by means of dendritic patch recordings and simultaneous calcium imaging. Pairing of subthreshold excitatory postsynaptic potentials (EPSPs) with back-propagating action potentials resulted in an amplification of dendritic action potentials and evoked calcium influx near the site of synaptic input. This pairing also induced a robust LTP, which was reduced when EPSPs were paired with non-back-propagating action potentials or when stimuli were unpaired. Action potentials thus provide a synaptically controlled, associative signal to the dendrites for Hebbian modifications of synaptic strength.

BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons

“…It is important to note that our results do not contradict those of Magee and Johnston (Magee and Johnston, 1997), who found that pairing EPSPs with bAPs evoked larger Ca 2+ elevations than bAP alone, for two reasons. First, Magee and Johnston (1997) imaged the main primary apical dendrite, whereas we have imaged the smaller radial branches off the main primary dendrite, recently dubbed "radial oblique dendrites" by the same authors Losonczy and Magee, 2006). We focused on these secondary branches because they express a higher density of spines and of synaptic contacts than the main apical trunk, and because our prior work on BDNF-induced spine formation focused on these spiny secondary dendritic branches Pozzo-Miller, 2001, 2003;Alonso et al, 2004).…”

“…In addition, we have not addressed whether dendritic Ca 2+ signals evoked by different stimulation protocols have supra-or sublinear relationships, but rather calculated how much larger were the Ca 2+ signals evoked by coincident EPSP-bAPs compared to those evoked by bAPs alone. This parameter is relevant to dendritic and synaptic function because pairing EPSPs with bAPs resulted in the amplification of dendritic action potentials and the resultant Ca 2+ elevations, as well as potentiation of synaptic potentials (Magee and Johnston, 1997). It is important to note that our results do not contradict those of Magee and Johnston (Magee and Johnston, 1997), who found that pairing EPSPs with bAPs evoked larger Ca 2+ elevations than bAP alone, for two reasons.…”

“…This parameter is relevant to dendritic and synaptic function because pairing EPSPs with bAPs resulted in the amplification of dendritic action potentials and the resultant Ca 2+ elevations, as well as potentiation of synaptic potentials (Magee and Johnston, 1997). It is important to note that our results do not contradict those of Magee and Johnston (Magee and Johnston, 1997), who found that pairing EPSPs with bAPs evoked larger Ca 2+ elevations than bAP alone, for two reasons. First, Magee and Johnston (1997) imaged the main primary apical dendrite, whereas we have imaged the smaller radial branches off the main primary dendrite, recently dubbed "radial oblique dendrites" by the same authors Losonczy and Magee, 2006).…”

“…These radial oblique dendrites have been shown to have different properties than the main apical trunk, including the amplitude of Ca 2+ signals evoked by bAPs , and the generation of local dendritic spikes involving Na + , Ca 2+ , and K + channels (Losonczy and Magee, 2006). Another potential reason for the difference with the Magee and Johnston (1997) observations is the fact that those studies were performed in acute hippocampal slices, whereas our measurements were done in organotypic slice cultures, a requirement for the long-term exposure to BDNF. Furthermore, our control slices have been kept in serum-free media to avoid the confounding effects of unknown growth factors in the equine serum, a consistently used and well-accepted control in neurotrophin studies in vitro.…”

Complexity of calcium signaling in synaptic spines

“…Induction of STDP is dependent on NMDAR and intracellular Ca 2þ , and partial blockade of NMDARs can induce LTD with a positively correlated pairing protocol. (23) In fact, pairings of pre-beforepost result in a superlinear increase in [Ca 2þ ] i (39)(40)(41)(42)(43) and postbefore-pre pairings result in a sublinear increase in [Ca 2þ ] i . (41) Thus, although the exact mechanisms remain unknown, it is likely that this form of synaptic plasticity shares many properties with the traditional, frequency-dependent forms of LTP and LTD. …”