Simultaneous induction of pathway-specific potentiation and depression in networks of cortical neurons

Activity-dependent modification of synaptic efficacy is widely recognized a s a cellular basis of learning, memory, and developmental plasticity. Littl e is known, however, of the consequences of such modification on network ac tivity. Using electrode arrays, we examined how a single, localized tetanic stimulus affects the firing of up to 72 neurons recorded simultaneously in cultured networks of cortical neurons, in response to activation through 6 4 different test stimulus pathways. The same tetanus produced potentiated t ransmission in some stimulus pathways and depressed transmission in others. Unexpectedly, responses were homogeneous: for any one stimulus pathway, ne uronal responses were either all enhanced or all depressed. Cross-correlati on of responses with the responses elicited through the tetanized site reve aled that both enhanced and depressed responses followed a common principle : activity that was closely correlated before tetanus with spikes elicited through the tetanized pathway was enhanced, whereas activity outside a 40-m s time window of correlation to tetanic pathway spikes was depressed. Respo nse homogeneity could result from pathway-specific recurrently excitatory c ircuits, whose gain is increased or decreased by the tetanus, according to its cross-correlation with the tetanized pathway response. The results show how spatial responses following localized tetanic stimuli, although comple x, can be accounted for by a simple rule for activity-dependent modificatio n.