A population of nicotinic receptors is associated with thalamocortical afferents in the adult rat: Laminal and areal analysis

Abstract

In the adult rat brain, a prominent population of nicotinic cholinoceptors binds 3H-nicotine with nanomolar affinity. These receptors are abundant in most thalamic nuclei and in neocortical layers 3/4, which receive a major thalamic input. To test whether cortical nicotinic receptors are associated with thalamocortical afferents, unilateral excitotoxic (N-methyl-D-aspartate) lesions were made in one of four thalamic nuclear groups (anterior, ventral, medial geniculate, or dorsal lateral geniculate) or in temporal cortex. After 1 or 4 weeks of survival, cortical 3H-nicotine binding was quantified via autoradiography. Thalamic lesions resulted in a partial loss of 3H-nicotine binding in ipsilateral cerebral cortex. In each thalamic lesion group, the greatest decrease (35-45%) occurred within the cortical layers and area (i.e., cingulate, parietal, temporal, or occipital cortex) receiving the densest thalamocortical innervation. Binding of 3H-nicotine was also reduced within the thalamus local to the lesion, particularly at the longer survival time. Saturation analysis, performed in frontoparietal cortical tissue homogenates following ventral thalamic lesions, revealed a significant (34%) reduction in receptor density but not affinity. Direct excitotoxic lesions of the neocortex (temporal cortex) tended to preserve 3H-nicotine binding in layers 3/4, despite local neuronal loss. These results, taken with other published findings, suggest that some nicotinic cholinoceptors in adult rat cerebral cortex are located on thalamocortical terminals. This organizing principle appears to apply not only to sensory and motor relay projections but also to association nuclei that project to allocortical areas. These receptors may provide a local mechanism for nicotinic cholinergic modulation of thalamocortical input.

Nicotine Induces Glutamate Release from Thalamocortical Terminals in Prefrontal Cortex

“…Thalamocortical projections are known to contain nicotinic receptors (Gil et al, 1997), and thalamic lesions have been shown to markedly reduce nicotine binding in the midlayers of cortex (Prusky et al, 1987;Sahin et al, 1992;Lavine et al, 1997;Gioanni et al, 1999). In order to test the hypothesis that nicotine triggers action potentials preferentially in thalamocortical terminals of the prefrontal cortex, we made unilateral radiofrequency lesions in the anterior thalamus in five animals and performed sham lesions in three animals.…”

“…The significance of any treatment on sEPSC frequency was assessed with Kolmogorov-Smirnov analysis for each neuron (data from the peak 20 s compared to 20 s of baseline); Po0.01 was considered significant. Where described in text and figures, Student's t-tests were used to compare responses from several neurons (Prusky et al, 1987;Sahin et al, 1992;Lavine et al, 1997;Gioanni et al, 1999). Baseline levels of sEPSCs were similar in mean and range across groups of neurons, and analysis by one-way ANOVA across experimental groups revealed no significant effect of group (rats, lesioned rats, wild-type or knockout mice) on baseline sEPSCs.…”

“…The result is consistent with work by Gil et al (1997) showing that nicotine modulates electrically evoked thalamocortical, but not corticocortical, glutamate release in superficial layers of the somatosensory cortex. It is also consistent with anatomical work showing that thalamic lesions decrease nicotine binding in the midlayers of the cortex (Prusky et al, 1987;Sahin et al, 1992;Lavine et al, 1997;Gioanni et al, 1999).…”

“…There was reason to think that the nicotinic-induced increase in glutamate release might be the latter type of sEPSCs, those mediated by spiking, so we assessed the effects of blocking action potentials and highvoltage-activated calcium channels. Previous work suggested that the glutamate release may be selectively from thalamocortical nerve terminals (Prusky et al, 1987;Sahin et al, 1992;Lavine et al, 1997;Gioanni et al, 1999). We give evidence that it is virtually abolished by thalamic lesions.…”

Mutated Nicotinic Receptors Responsible for Autosomal Dominant Nocturnal Frontal Lobe Epilepsy are More Sensitive to Carbamazepine

“…Nicotinic receptors have been identified on the thalamocortical cells that receive the cholinergic input from the tegmentum. It was shown in the rat that these receptors probably result from the assembly of the a4 and p2 subunits (63). In the cat, the activation of the cholinergic input of the thalamus was shown to disrupt spindle activity by an initial fast membrane depolarization of thalamocortical neurons, mediated by nicotinic receptors, followed by a prolonged depolarization mediated by muscarinic receptors (62).…”