LAMINAR SELECTIVITY OF THE CHOLINERGIC SUPPRESSION OF SYNAPTIC TRANSMISSION IN RAT HIPPOCAMPAL REGION CA1 - COMPUTATIONAL MODELING AND BRAIN SLICE PHYSIOLOGY

ACh may set the dynamics of cortical function to those appropriate for learning new information. In models of the putative associative memor y function of piriform cortex, selective suppression of intrinsic but not afferent fiber synaptic transmission by ACh prevents recall of pre vious input from interfering with the learning of new input (Hasselmo, 1993). Selective cholinergic suppression may play a similar role in t he hippocampal formation, where Schaffer collateral synapses in stratu m radiatum (s. rad) may store associations between activity in region CA3 and the entorhinal cortex input to region CA1 terminating in strat um lacunosum-moleculare (s. l-m). A computational model of region CA1 predicts that for effective associative memory function of the Schaffe r collaterals, cholinergic suppression of synaptic transmission should be stronger in s. rad than in s. l-m. In the hippocampal slice prepar ation, we tested the effect of the cholinergic agonist carbachol (0.01 -500 mu M) On synaptic transmission in s. rad and s. l-m. Stimulating and recording electrodes were simultaneously placed in both layers, al lowing analysis of the effect of carbachol on synaptic potentials in b oth layers during the same perfusion in each slice. Carbachol produced a significantly stronger suppression of stimulus-evoked EPSPs in s. r ad than in s. l-m at all concentrations greater than 1 mu M. At 100 mu M, EPSP initial slopes were suppressed by 89.1 +/- 3.0% in s. rad, bu t only by 40.1 +/- 4.1 % in s. l-m. The muscarinic antagonist atropine (1 mu M) blocked cholinergic suppression in both layers. These data s upport the hypothesis that synaptic modification of the Schaffer colla terals may store associations between activity in region CA3 and the a fferent input to region CA1 from the entorhinal cortex. In simulations , feedback regulation of cholinergic modulation based on activity in r egion CA1 sets the appropriate dynamics of learning for novel associat ions, and recall for familiar associations.