Although spike-timing-dependent plasticity (STDP) is well characterized when pre- and postsynaptic spikes are paired with a given time lag, how this generalizes for more complex spike-trains is unclear. Recent experiments demonstrate that contributions to synaptic plasticity from different spike pairs within a spike train do not add linearly. In the visual cortex conditioning with spike triplets shows that the effect of the first spike pair dominates over the second. Using a previously proposed calcium-dependent plasticity model, we show that short-term synaptic dynamics and interaction between successive back-propagating action potentials (BPAP) may jointly account for the nonlinearities observed. Paired-pulse depression and attenuation of BPAPs are incorporated into the model through the use-dependent depletion of pre- and postsynaptic resources, respectively. Simulations suggest that these processes may play critical roles in determining how STDP operates in the context of natural spike-trains.

LC, Shouval LN. Effect of stochastic synaptic and dendritic dynamics on synaptic plasticity in visual cortex and hippocampus. J Neurophysiol 97: 375-386, 2007. First published October 11, 2006 doi:10.1152/jn.00895.2006. Various forms of synaptic plasticity, including spike timing-dependent plasticity, can be accounted for by calcium-dependent models of synaptic plasticity. However, recent results in which synaptic plasticity is induced by multi-spike protocols cannot simply be accounted for by linear superposition of plasticity due to spike pairs or by existing calcium-dependent models. In this paper, we show that multi-spike protocols can be accounted for if, in addition to the dynamics of back-propagating action potentials, stochastic synaptic dynamics are taken into account. We show that a stochastic implementation can account for the data better than a deterministic implementation and is also more robust. Our results demonstrate that differences between experimental results obtained in hippocampus and visual cortex can be accounted for by the different synaptic and dendritic dynamics in these two systems.

The octopus cells of the posteroventral cochlear nucleus receive inputs from auditory-nerve fibers and form one of the major ascending auditory pathways. They respond to acoustic and electrical stimulation transiently and are believed to carry temporal information in the precise timing of their action potentials. The mechanism whereby onset responses are generated is not clear. Proposals aimed at elucidating the mechanism range from neural circuitry and/or inhibition, "depolarization block" (or inactivation of Na+ channels), and the involvement of a 4-aminopyridine (4-AP)-sensitive, low-threshold channel (K(LT)). In the present study, we used a compartment model to investigate possible mechanisms. The model cell contains a soma, an axon, and four passive dendrites. Four kinds of ionic channels were included in the soma compartment: the Hodgkin-Huxley-like Na+ and K+ channels, a 4-AP-sensitive, low-threshold channel, K(LT), and a Cs+-sensitive, hyperpolarization-activated inward rectifier, Ih. DC currents and half-wave-rectified sine waves were used as stimuli. Our results showed that an onset response can be generated in the absence of neuronal circuitry of any form, thus suggesting that the onset response in octopus cells is regulated intrinsically. Among the many factors involved, low-input impedance, partly contributed by Ih, appears to be essential to the basic onset response pattern; also, the K(LT) conductance plays a major role, whereas the inactivation of Na+ channels probably plays only a secondary role. The dynamics of Ih also can modify the response pattern, but due to its slow kinetics, its role is probably limited to longer-term regulation under the conditions simulated in this study.

Multiplicative computation is a basic operation that is crucial for neural information processing, but examples of multiplication by neural pathways that perform well-defined sensorimotor transformations are scarce. Here in behaving monkeys, we identified a multiplication of vestibular and eye position signals in the vestibulo-ocular reflex (VOR). Monkeys were trained to maintain fixation on visual targets at different horizontal locations and received brief unilateral acoustic clicks (1 ms, rarefaction, 85 approximately 110 db NHL) that were delivered into one of their external ear canals. We found that both the click-evoked horizontal eye movement responses and the click-evoked neuronal responses of the abducens neurons exhibited linear dependencies on horizontal conjugate eye position, indicating that the interaction of vestibular and horizontal conjugate eye position was multiplicative. Latency analysis further indicated that the site of the multiplication was within the direct VOR pathways. Based on these results, we propose a novel neural mechanism that implements the VOR gain modulation by fixation distance and gaze eccentricity. In this mechanism, the vestibular signal from a single labyrinth interacts multiplicatively with the position signals of each eye (Principle of Multiplication). These effects, however, interact additively with the other labyrinth (Principle of Addition). Our analysis suggests that the new mechanism can implement the VOR gain modulation by fixation distance and gaze eccentricity within the direct VOR pathways.

The onset response pattern displayed by octopus cells has been attributed to intrinsic membrane properties, low membrane impedance, and/or synaptic inputs. Although the importance of a low membrane impedance generally is acknowledged as an essential component, views differ on the role that ion channels play in producing the onset response. In this study, we use a computer model to investigate the contributions of ion channels to the responses of octopus cells. Simulations using current ramps indicate that, during the "ramp-up" stage, the membrane depolarizes, activating a low-threshold K(+) channel, K(LT), which increases membrane conductance and dynamically increases the current required to evoke an action potential. As a result, the model is sensitive to the rate that membrane potential changes when initiating an action potential. Results obtained when experimentally recorded spike trains of auditory-nerve fibers served as model inputs (simulating acoustic stimulation) demonstrate that a model with K(LT) conductance as the dominant conductance produces realistic onset response patterns. Systematically replacing the K(LT) conductance by a h-type conductance (which corresponds to a hyperpolarization-activated inward rectifier current, I(h)) or by a leakage conductance reduces the model's sensitivity to rate of change in membrane potential, and the model's response to "acoustic stimulation" becomes more chopper-like. Increasing the h-type conductance while maintaining a large K(LT) conductance causes an increase in threshold to both current steps and acoustic stimulation but does not significantly affect the model's sensitivity to rate of change in membrane potential and the onset response pattern under acoustic stimulation. These findings support the idea that K(LT), which is activated during depolarization, is the primary membrane conductance determining the response properties of octopus cells, and its dynamic role cannot be provided by a static membrane conductance. On the other hand, I(h), which is activated during hyperpolarization, does not play a large role in the basic onset response pattern but may regulate response threshold through its contribution to the membrane conductance.