Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential

Vol 441|8 June 2006|doi:10.1038/nature04720LETTERSModulation of intracortical synaptic potentials by

presynaptic somatic membrane potentialYousheng Shu1, Andrea Hasenstaub1, Alvaro Duque1, Yuguo Yu1 & David A. McCormick1Traditionally, neuronal operations in the cerebral cortex have

been viewed as occurring through the interaction of synaptic

potentials in the dendrite and soma, followed by the initiation

of an action potential, typically in the axon1,2. Propagation of this

action potential to the synaptic terminals is widely believed to be

the only form of rapid communication of information between the

soma and axonal synapses, and hence to postsynaptic neurons.

Here we show that the voltage fluctuations associated with

dendrosomatic synaptic activity propagate significant distances

along the axon, and that modest changes in the somatic membrane

potential of the presynaptic neuron modulate the amplitude

and duration of axonal action potentials and, through a Ca21-dependent mechanism, the average amplitude of the postsynaptic

potential evoked by these spikes. These results indicate that

synaptic activity in the dendrite and soma controls not only the

pattern of action potentials generated, but also the amplitude of

the synaptic potentials that these action potentials initiate in local

cortical circuits, resulting in synaptic transmission that is a

mixture of triggered and graded (analogue) signals.To examine the properties of monosynaptic excitatory connections within the cortex, we obtained whole-cell recordings from

nearby (within 60m m) and synaptically connected pairs of layer 5

pyramidal cells in ferret prefrontal cortical slices (Fig. 1, n 28

paired recordings; Supplementary Fig. 1). As expected, activation of

an action potential in the presynaptic neuron with a short (1 ms)

depolarizing current pulse resulted in an excitatory postsynaptic

potential (EPSP; Fig. 1b). However, we found that steady depolarization of the soma of the presynaptic neuron by approximately

1015 mV from the resting membrane potential (average 262 mV)

to near the firing threshold (average 248 mV) resulted in a substantial and statistically significant increase in the average EPSP

amplitude evoked in the postsynaptic cell (18/28 synaptic connections in 28 unique paired recordings; Fig. 1b, e), even though this

depolarization had no significant effect on the resting membrane

potential of the postsynaptic cell. The median significant enhancement was 29% (ranging from 12 to 69%, with one outlier at 194%;

Fig. 1e) and was reversible (Fig. 1b).We observed the enhancing effect of...