Behavioural Brain Research 148 (2004) 55–71 Research report Pretraining or previous non-spatial experience improves spatial learning in the Morris water maze of nucleus basalis lesioned rats Francisco A. Nieto-Escámez a , Fernando Sánchez-Santed a,∗ , Jan P.C. de Bruin b a Departamento de Neurociencia y Ciencias de la Salud, Universidad de Almer´ ıa, Ctra. Sacramento s/n 04120, Almer´ ıa, Spain b Graduate School of Neurosciences Amsterdam, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands Received 7 April 2003; received in revised form 6 May 2003; accepted 7 May 2003 Abstract Previous experiments have shown that infusions of ibotenic acid in the nucleus basalis magnocellularis (NBM) induce a strong impairment in spatial navigation for a hidden platform in the Morris water maze. This effect was initially attributed to a cholinergic deficit, but later studies showed that performance level did not correlate with the degree of cholinergic denervation. Therefore, this impairment is due to a combined cholinergic and non-cholinergic deficit. However, it is not clear in which particular processes the NBM is involved. In this study we have evaluated the origin of behavioural impairment in spatial navigation in the water maze after an ibotenic acid-induced lesion of NBM. In the first experiment, Wistar rats were trained preoperatively in an allocentric navigation task. Postoperatively, they were tested in the same task. All lesioned animals showed a performance level similar to controls. Lesions did not impede the acquisition of new positions in the water maze, nor did affect the ability of animals to remember new platform positions after an intertrial interval of 20 s, even if animals had received only allocentric experience with the platform position, or allocentric and path integration information concurrently. Lesions also failed to affect the ability to locate a hidden platform in a new environment. However, hippocampal infusions of scopolamine (5 g) produced a severe impairment in NBM-damaged animals, without impairing performance of controls. In the second experiment Wistar rats with the same lesion were first trained in a visual-guided task in the water maze, and subsequently evaluated in the spatial task. In both tasks lesioned animals were not different from controls. These results suggest that the NBM played an important role during acquisition phases but not in the execution of spatial navigation. Moreover, the excessive emotional response displayed by lesioned animals is postulated as a relevant cause for the impairment observed in spatial navigation after NBM damage. © 2003 Elsevier B.V. All rights reserved. Keywords: Memory; Ibotenic acid; Basal forebrain; Hippocampus; Scopolamine 1. Introduction The nucleus basalis magnocellularis (NBM) of the rat contains large cholinergic neurons, distributed along the Abbreviations: Acb, accumbens nucleus; Acd, dorsal part of the ante- rior cingulate cortex; AChE, acetylcholinesterase; AP5, d(-)-2-amino-5- phosphonopentanoic acid; cc, corpus callosum; ChAT, choline acetyltrans- ferase; CTA, conditioned taste aversion; CA1, field CA1 of hippocampus; CA2, field CA2 of hippocampus; CA3, field CA3 of hippocampus; fi, fimbria; fmi, forceps minor corpus callosum; Fr1, frontal area 1; Fr2, frontal area 2; Fr3, frontal area 3; GABA, -aminobutyric acid; HL, hindlimb area of cortex; IL, infralimbic area; ITI, intertrial interval; LTP, long-term potentiation; NBM, nucleus basalis magnocellularis; NMDA, N-methyl-d-aspartate; Par1, parietal area 1; Pir, piriform cortex; PBS, phosphate-buffered saline; PFC, prefrontal cortex; PL, prelimbic area; TTX, tetrodotoxin; Tu, tuberculum olfactorium ∗ Corresponding author. Tel.: +34-950-015868; fax: +34-950-015473. E-mail address: pnieto@ual.es (F. S´ anchez-Santed). substantia innominata, and similarly to the human nu- cleus basalis of Meynert is anatomically complex, with heterogeneous and intermingled populations of neurons [99]. Most magnocellular neurons are cholinergic (some of them are GABAergic), whereas the smaller neurons are non-cholinergic, i.e. GABAergic, and neuropeptidergic [27,45–47,60,99]. The NBM receives strong aminergic, cholinergic, GAB- Aergic, glutamatergic and neuropeptidergic afferents [42,43, 59,98,121–123] and is the main source of cortical acetyl- choline involved in cognition [27,36,97]. Thus, the decline in cognitive performance during ageing and Alzheimer disease has been related to the degeneration of the cortical-NBM cholinergic system [24,30,40,63,71,83,113,119]. Indeed, the NBM is one of the most vulnerable regions in ageing. A decrease of neurons and cortical cholinergic transmis- sion has been reported [26,37,64,75,101], accompanied by structural changes in NBM neurons during ageing [26,110]. 0166-4328/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0166-4328(03)00182-7