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J Neurophysiol 90: 2358-2366, 2003. First published July 2, 2003; doi:10.1152/jn.00262.2003
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Septal Modulation of Excitatory Transmission in Hippocampus

Laura Lee Colgin1, Enikö A. Kramár1, Christine M. Gall2 and Gary Lynch1

1 Department of Psychiatry and Human Behavior, University of California, Irvine, California 92612; 2 Department of Anatomy and Neurobiology, University of California, Irvine, California 92612

Submitted 19 March 2003; accepted in final form 1 July 2003

Application of the acetylcholinesterase inhibitor physostigmine to conventional hippocampal slices caused a significant reduction of field excitatory postsynaptic potentials (EPSPs) elicited by single pulse stimulation to the medial perforant path. Similar but smaller effects were obtained in the lateral perforant path and other excitatory pathways within hippocampus. The reductions were blocked by atropine, were not accompanied by evident changes in the EPSP waveform, and were eliminated by lesions to the cholinergic septo-hippocampal projections. Antidromic responses to mossy fiber stimulation, recorded in stratum granulosum, were not affected by the drug. However, paired-pulse facilitation was reliably increased, indicating that the depressed synaptic responses were secondary to reductions in transmitter release. The absence of cholinergic axo-axonic connections in the molecular layer suggests that physostigmine reduces presynaptic release by increasing retrograde signaling from the granule cells. In accord with this, an antagonist of the CB1 cannabinoid receptor eliminated the effects of physostigmine on synaptic responses, while an antagonist of the presynaptically located m2 muscarinic acetylcholine receptor did not. This is in contrast to previously reported effects involving application of cholinergic agonists, in which presynaptic inhibition likely results from direct activation of presynaptically located muscarinic receptors. In summary, it is proposed that the cholinergic inputs from the septum to the middle molecular layer modulate, via endocannabinoid release, the potency of the primary excitatory afferent of hippocampus.

Address for reprint requests and other correspondence: L. L. Colgin, Dept. of Psychiatry and Human Behavior, Univ. of California, Irvine, 101 Theory, Suite 250, Irvine, CA 92612 (E-mail: lcolgin{at}uci.edu).




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L. L. Colgin, D. Kubota, F. A. Brucher, Y. Jia, E. Branyan, C. M. Gall, and G. Lynch
Spontaneous Waves in the Dentate Gyrus of Slices From the Ventral Hippocampus
J Neurophysiol, December 1, 2004; 92(6): 3385 - 3398.
[Abstract] [Full Text] [PDF]


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