ACh may help set the dynamics within neural systems to facilitate the learning of new information. Neural models have shown that if new information is encoded at the same time as retrieval of existing information already stored, the memories will interfere with each other. Structures such as the hippocampus have a distinct laminar organization of inputs that allows this hypothesis to be tested. In region CA1 of the rat hippocampus, the cholinergic agonist carbachol (CCh) suppresses transmission in stratum radiatum (SR), at synapses of the Schaffer collateral projection from CA3, while having lesser effects in stratum lacunosum-moleculare (SLM), the perforant path projection from entorhinal cortex (Hasselmo and Schnell, 1994). The current research extends support of this selectivity by demonstrating laminar effects in region CA3. CCh caused significantly greater suppression in SR than in SLM at low concentrations, while the difference in suppression was not significant at higher concentrations. Differences in paired-pulse facilitation suggest pre-synaptic inhibition substantially contributes to the suppression and is highly concentration and stratum dependent. This selective suppression of the recurrent excitation would be appropriate to set CA3 dynamics to prevent runaway modification of the synapses of excitatory recurrent collaterals by reducing the influence of previously stored associations and allowing incoming information from the perforant path to have a predominant influence on neural activity. Keywords perforant path; recurrent collaterals; presynaptic; muscarinic; acetylcholine Acetylcholine (ACh) has been shown to play a vital role in learning and memory ((for a review see Hagan and Morris, 1988;Rasmusson, 2000)). An extensive range of experiments using ACh agonists and antagonists (Davis et al., 1971;Ghoneim and Mewaldt, 1977;Kopelman, 1986;Hagan and Morris, 1988;Whishaw, 1989;Fibiger, 1991) indicate a vital role for ACh in the encoding of new memories. Selective lesions of the primary cholinergic input to the hippocampus using IgG-192 saporin have been shown to influence attention and various aspects of cognitive behavior (Baxter et al., 1997;Janisiewicz et al., 2004), including causing transient impairments of spatial memory function (Vuckovich et al., 2004), but they may not Corresponding Author: 5858 Horton Street, Suite 200, Emeryville, CA 94608, Email: tkremin@gallo.UCSF.edu, . Section Editor: Dr. Geoffrey Schoenbaum Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. always have strong mnemonic effects as some levels of hippocampal ACh may remain (C...
