This article reviews evidence from studies employing colchicine-induced granule cell loss in the adult rat brain, and irradiation-induced hypoplasia of the neonatal dentate gyrus, on the performance of spatial and non-spatial behavioral tasks. The general picture emerging from this analysis reveals that the dentate gyrus granule cells are critically involved in spatial behavior, particularly when this requires the adoption of place strategies. This notion also provides an explanation for the behavioral effects of dentate gyrus granule cell loss seen in apparently non-spatial tasks.

1 (a3) 2 (b4) 3 is the most abundant type of neuronal nicotinic ACh receptor (nAChR) mediating cholinergic actions on the autonomic nervous system. Studies to refine or devise drugs selectively acting on (a3) 2 (b4) 3 receptors would benefit from a detailed description of the hitherto unclear agonist-binding domain. 2 The present study reports a three-dimensional model for the ligand-binding domain (LBD) of this receptor either in its unoccupied or agonist-bound conformation. The receptor model was based on the structure of the acetylcholine-binding protein (AChBP), and was obtained using molecular modelling techniques. 3 ACh, nicotine and cytisine (full agonists), muscarine (a selective agonist of muscarinic ACh receptors) and the allosteric modulator eserine were docked into the binding pockets of the receptor model. Simulated agonist -receptor complexes were compared with the agonist-binding complex of the AChBP, as well as of the (a4) 2 (b2) 3 type of nAChR, which is the commonest in the brain. 4 Agonist docking identified discrete amino-acid residues of the b subunits important for pharmacological selectivity of nAChRs. The predicted affinity of muscarine for the nAChR was low, suggesting the present model to be suitable for effective discrimination of nicotinic agonist binding versus nonselective cholinergic binding. Furthermore, the current model outlined a potential binding site for the allosteric modulator eserine, the site of action of which has remained elusive. 5 The present LBD model of the receptor in its free state provides a novel structural framework to interpret experimental observations and a useful template for future investigations to develop (a3) 2 (b4) 3 -selective ligands.

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These data implicate the alpha(5) integrin subunit in Fn-f mediated activities, consistent with a role for the alpha(5)beta(1) integrin in this pathway.