Cooperativity and Frequency Dependence of Spike Timing-Dependent Plasticity in Visual Cortical Layer-5 Pairs.

Sjöström PJ, Turrigiano GG, Nelson SB, Soc Neurosci Abstr, 923.11, (2001).

Long-term potentiation (LTP) or depression (LTD) can be produced by the millisecond timing of pre- and postsynaptic spikes, a concept termed spike timing-dependent plasticity (STDP). Classical LTP/LTD exhibits cooperativity and frequency dependence. We examined whether STDP shares these features, using whole-cell recordings of synaptically connected, thick tufted layer-5 neurons in rat visual cortex.

Despite providing the postsynaptic spike, STDP-based LTP evoked at low frequency (<10 Hz) required additional depolarization either via somatic current injection (n=7), or via activation of multiple inputs (n=6). Hence at low frequency unitary inputs must cooperate to produce LTP.

Could this depolarization requirement contribute to the frequency dependence of STDP-based LTP? During postsynaptic bursts (10 Hz) cells did not fully repolarize between spikes. Amounts of LTP and this residual depolarization were correlated. Furthermore, STDP-based LTP at 40 Hz (5314% LTP, n=11, p<0.01) was blocked by brief hyperpolarizations between successive spikes (09.1% LTP, n=7, p=0.48). This suggests that the frequency dependence of STDP-based LTP is at least partly due to residual depolarization.

The LTD side of STDP did not depend on initial depolarization (n=38) or frequency (0.1-20 Hz, n=14), but was absent at high frequency (40-50 Hz, n=15). LTP may win out over LTD when there are multiple interactions between pre- and postsynaptic spikes.

In conclusion, STDP exhibits two hallmark features of classical LTP/LTD: frequency dependence and cooperativity.

(Funded by NIH and the Sloan Foundation.)