RESUMEN
The advent of the selective cholinergic toxin, 192 IgG-saporin, dramatically shaped subsequent research on the role of the basal forebrain in learning and memory. In particular, several articles (including the authors' 1995 Behavioral Neuroscience paper; M. G. Baxter, D. J. Bucci, L. K., Gorman, R. G. Wiley, & M. Gallagher, 1995) revealed that selective removal of basal forebrain cholinergic neurons had surprisingly little effect on spatial learning and memory. Here, as part of the series commemorating the 30th anniversary of Behavioral Neuroscience, we describe how our earlier findings prompted a reconsideration of the cholinergic contribution to cognitive function and also led to several new research directions, including renewed interest in basal forebrain GABA-ergic neurons and cholinergic contributions to neurocognitive development. The authors also describe how the successful use of 192 IgG-saporin led to the development and popularity of a wide range of selective new neurotoxic agents. Finally, they consider the utility of the permanent lesion approach in the wake of new transgenic and optogenetic methods.
Asunto(s)
Anticuerpos Monoclonales/historia , Colinérgicos/historia , Neuronas Colinérgicas/fisiología , Inmunotoxinas/historia , Aprendizaje/fisiología , Memoria/fisiología , Proteínas Inactivadoras de Ribosomas Tipo 1/historia , Animales , Masculino , SaporinasRESUMEN
Male Long-Evans rats were given injections of either 192 IgG-saporin, an apparently selective toxin for basal forebrain cholinergic neurons (LES), or vehicle (CON) into either the medial septum and vertical limb of the diagonal band (MS/VDB) or bilaterally into the nucleus basalis magnocellularis and substantia innominata (nBM/SI). Place discrimination in the Morris water maze assessed spatial learning, and a trial-unique matching-to-place task in the water maze assessed memory for place information over varying delays. MS/VDB-LES and nBM/SI-LES rats were not impaired relative to CON rats in acquisition of the place discrimination, but were mildly impaired relative to CON rats in performance of the memory task even at the shortest delay, suggesting a nonmnemonic deficit. These results contrast with effects of less selective lesions, which have been taken to support a role for basal forebrain cholinergic neurons in learning and memory.
Asunto(s)
Anticuerpos Monoclonales/historia , Colinérgicos/historia , Neuronas Colinérgicas/fisiología , Inmunotoxinas/historia , Aprendizaje/fisiología , Memoria/fisiología , Proteínas Inactivadoras de Ribosomas Tipo 1/historia , Animales , Anticuerpos Monoclonales/toxicidad , Colinérgicos/toxicidad , Neuronas Colinérgicas/efectos de los fármacos , Historia del Siglo XX , Inmunotoxinas/toxicidad , Aprendizaje/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Ratas , Ratas Long-Evans , Proteínas Inactivadoras de Ribosomas Tipo 1/toxicidad , SaporinasRESUMEN
Salvador Zubirán submitted his thesis for his MD degree in 1923. This thesis falls within the context of the new Mexican physiological medicine and denotes the visionary character of its author. Zubirán appears here as the introducer in Mexico of the physiopharmacological approach in autonomic nervous system disorders.