Faculty Bibliography

The strength of the connection between two neurons can be modified by activity, in a way that depends on the timing of neuronal firing on either side of the synapse. This spike-timing-dependent plasticity (STDP) has been studied by systematically varying the intervals between pre- and postsynaptic spikes. Here we studied how STDP operates in the context of more natural spike trains. We found that in visual cortical slices the contribution of each pre-/postsynaptic spike pair to synaptic modification depends not only on the interval between the pair, but also on the timing of preceding spikes. The efficacy of each spike in synaptic modification was suppressed by the preceding spike in the same neuron, occurring within several tens of milliseconds. The direction and magnitude of synaptic modifications induced by spike patterns recorded in vivo in response to natural visual stimuli were well predicted by incorporating the suppressive inter-spike interaction within each neuron. Thus, activity-induced synaptic modification depends not only on the relative spike timing between the neurons, but also on the spiking pattern within each neuron. For natural spike trains, the timing of the first spike in each burst is dominant in synaptic modification

The flow of activity in the cortical microcircuitry is poorly understood. We use calcium imaging to reconstruct, with millisecond and single-cell resolution, the spontaneous activity of populations of neurons in unstimulated slices from mouse visual cortex. We find spontaneous activity correlated among networks of layer 5 pyramidal cells. Synchronous ensembles occupy overlapping territories, often share neurons, and are repeatedly activated. Sets of neurons are also sequentially activated numerous times. Network synchronization and sequential correlations are blocked by glutamatergic antagonists, even though spontaneous firing persists in many 'autonomously active' neurons. This autonomous activity is periodic and depends on hyperpolarization-activated cationic (H) and persistent sodium (Na(p)) currents. We conclude that the isolated neocortical microcircuit generates spontaneous activity, mediated by a combination of intrinsic and circuit mechanisms, and that this activity can be temporally precise

Long-term facilitation at the crayfish opener muscle is elicited by prolonged high frequency stimulation, and arises from an increase in functional active zones, resulting in increased transmitter release. LTF induction depends critically upon presynaptic calcium accumulation and calcineurin (PP2B) activity. The protein synthesis dependence of this synaptic strengthening was investigated. LTF occurred without transcription, but the translation inhibitors cycloheximide and anisomycin, or local presynaptic injection of mRNA cap analog m7GpppG, impaired LTF expression. Both MAP kinase and phosphatidylinositol 3-OH kinase (PI3K) activation are implicated in this rapamycin-sensitive synaptic potentiation. This study defines an important role for protein synthesis in the expression of activity-dependent plasticity, and provides mechanistic insight for the induction of this process at presynaptic sites