Multiple heteroreceptors on limbic thalamic axons: M2 acetylcholine, serotonin1B, beta 2-adrenoceptors, mu-opioid, and neurotensin.

Ligand binding to many transmitter receptors is much higher in layer Ia of rat posterior cingulate cortex than it is in other layers, and this is where most axons from the anterior thalamus terminate. The present study explores the possibility that a number of receptors may be expressed on axons from limbic thalamic nuclei that terminate in layer Ia. Unilateral thalamic lesions were placed in rats and, 2 weeks later, five ligand binding protocols, coverslip autoradiography, and single grain counting techniques were used to quantify binding in control and ablated hemispheres. Binding to the following receptor subtypes was analyzed: M2 acetylcholine, 3H-oxotremorine-M, or 3H-AF-DX 116 with 50 nM pirenzepine; serotonin1B, 125I-(-)-cyanopindolol with 30 microM isoproterenol; beta 2-adrenoceptors, 125I-(-)-cyanopindolol with 1 microM serotonin and 10 microM atenolol; mu-opioid, 3H-T[r-D-Ala-Gly-MePhe-Gly-ol; neurotensin, 3H-neurotensin. Thalamic lesions reduced binding in two laminar patterns. In one pattern, there was a major reduction in binding in most superficial layers with that in layer Ia ranging from 50 to 70% for binding to M2 muscarinic and serotonin1B receptors. Binding to beta 2-adrenoceptors was also reduced in most superficial layers but to a lesser extent. In the second pattern, reductions were limited to layer I with losses in layer Ia of 20-30% for mu-opioid and neurotensin receptors. In no instance was layer Ia binding completely abolished (i.e., postlesion peaks remained). Since the transmitters for each of the five receptors analyzed in this study are not synthesized by anterior or laterodorsal thalamic neurons, these receptors are heteroreceptors. The greatest postlesion reduction in M2 binding was for AF-DX 116 and so most M2 heteroreceptors are of the "cardiac" subtype. Finally, the diverse population of heteroreceptors on limbic thalamic axons provides for presynaptic modulation by a wide range of transmitter systems and suggests that thalamocortical transmission may not be a simple, unmodulated event.