AUTORADIOGRAPHIC COMPARISON OF CHOLINERGIC AND OTHER TRANSMITTER RECEPTORS IN THE NORMAL HUMAN HIPPOCAMPUS

The vulnerability of the human hippocampal complex to disease, trauma, and aging indicates the necessity to target this area therapeutically . The distribution and density of transmitter receptors provide a rati onal basis for this approach, and in this study the topography of 11 d ifferent pharmacological sites is compared with the cholinergic innerv ation, which is particularly vulnerable in dementia. The regional dist ribution of cholinergic innervation to the normal adult human hippocam pus and adjacent cor-tex, marked by acetylcholinesterase (AChE) fiber and terminal reactivity, is notable for its concentration in CA2/3 of Ammon's horn and the dentate fascia. Neither nicotinic (high-affinity nicotine binding) nor muscarinic (''M1'' or ''M2'') cholinergic recept or binding paralleled this distribution. In Ammon's horn, 5-HT2 and ka inate receptor binding more closely resembled the pattern of AChE, bei ng concentrated in CA2-4 compared with CA1. By contrast, muscarinic M1 and M2, 5-HT1A, benzodiazepine (including zolpidem-insensitive bindin g), NMDA (MK801), and AMPA/QUIS receptors were higher in CA1 and/or su biculum. Kainate binding, like AChE, was high in CA4. 5-HT2 and nicoti nic binding partially mimicked the pattern of AChE around the granule layer. In the subicular complex and parahippocampal gyrus, where choli nergic activity is relatively lower, muscarinic, 5-HT1A, and benzodiaz epine binding were relatively high and the nicotinic receptor was rema rkable for its highest density compared to other areas examined. In st ratum lacunosum-moleculare of CA1, which was relatively low in AChE ac tivity, there was a dense band of nicotinic, M2, and benzodiazepine re ceptor binding. These observations, while reflecting the anatomical co mplexity of chemical signaling in the hippocampal region, indicate a u nique distribution for the nicotinic receptor and suggest that the cho linergic input may specifically interact with 5-HT and excitatory amin o acid systems via 5-HT2 and kainate receptor subtypes in governing si gnaling to the dentate and CA3 regions.