DIFFERENTIAL REGULATION OF NEOCORTICAL SYNAPSES BY NEUROMODULATORS AND ACTIVITY

Synapses are continually regulated by chemical modulators and by their own activity. We tested the specificity of regulation in two excitato ry pathways of the neocortex: thalamocortical (TC) synapses, which med iate specific inputs, and intracortical (IC) synapses, which mediate t he recombination of cortical information. Frequency-sensitive depressi on was much stronger in TC synapses than in IC synapses. The two synap se types were differentially sensitive to presynaptic neuromodulators: only IC synapses were suppressed by activation of GABA, receptors, on ly TC synapses were enhanced by nicotinic acetylcholine receptors, and muscarinic acetylcholine receptors suppressed both synapse types. Mod ulators also differentially altered the frequency sensitivity of the s ynapses. Our results suggest a mechanism by which the relative strengt h and dynamics of input and associational pathways of neocortex are re gulated during changes in behavioral state.