Behavioural Brain Research 121 (2001) 1 – 10 Research report Crossed unilateral lesions of medial forebrain bundle and either inferior temporal or frontal cortex impair object recognition memory in Rhesus monkeys Alexander Easton a, *, Amanda Parker b , David Gaffan a a Department of Experimental Psychology, Oxford Uniersity, South Parks Road, Oxford OX13UD, UK b School of Psychology, Uniersity of Nottingham, Nottingham, UK Received 11 September 2000; received in revised form 16 November 2000; accepted 16 November 2000 Abstract In monkeys, section of the fornix, amygdala and anterior temporal stem results in a severe anterograde amnesia. Immunolesions of the cholinergic cells of the basal forebrain suggest that this amnesia is a result of isolating the inferior temporal cortex and medial temporal lobe from their cholinergic basal forebrain afferents. In this experiment, six monkeys were trained in a delayed match-to-sample task and then received a section of the medial forebrain bundle in one hemisphere and an ablation of either the frontal or inferior temporal cortex in the opposite hemisphere. All the animals were severely impaired in the performance of this task following this surgery, and the severity of the impairment was independent of the cortical area from which the medial forebrain bundle was disconnected. These results support a model of fronto-temporal interaction via the basal forebrain in new learning, in which midbrain sites related to reward modulate the cholinergic basal forebrain activity. © 2001 Elsevier Science B.V. All rights reserved. Keywords: Basal forebrain; Frontal cortex; Inferior temporal cortex; Rhesus monkeys; Memory; Match-to-sample www.elsevier.com/locate/bbr 1. Introduction In Rhesus monkeys, bilateral sections of the fornix, amygdala and anterior temporal stem resulted in a dense anterograde amnesia with the relative sparing of pre-operatively taught material [13]. The cholinergic efferents from the basal forebrain to the inferior tempo- ral cortex and medial temporal lobe project through the fornix, amygdala and anterior temporal stem in mon- keys and humans [19,33]. In monkeys, isolating the inferior temporal cortex and medial temporal lobe from their cholinergic afferents by use of an immunotoxin specific for these cholinergic cells also results in a severe amnesia [9,29,30]. Bilateral lesions or cooling of frontal or inferior temporal cortex impair object-reward association learn- ing [14,22,35] and recognition memory [1,12,17,35]. In addition, the frontal and inferior temporal cortices must interact within the same hemisphere to allow normal recognition memory [25] and scene learning [5]. This interaction, however, is not via the direct cortico- cortical communication through the uncinate fascicle [4,11]. In combination with the evidence for the in- volvement of the basal forebrain in learning, then, Easton and Gaffan [6] have recently presented a model of new learning in which the frontal and inferior tem- poral cortices interact via the basal forebrain. In this model of fronto-temporal interactions via the basal forebrain, the frontal cortex sets the goal of the task and communicates this to the basal forebrain, which reinforces object representations in the inferior temporal cortex if those objects are associated with the attainment of the goal. This model raises the question * Corresponding author. Present address: A. Easton, School of Psychology, University of Nottingham, Nottingham, NG7 2RD, UK. Tel.: +44-1865-271413; fax: +44-1865-310447. E-mail address: ae@psychology.nottingham.ac.uk (A. Easton). 0166-4328/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved. PII: S0166-4328(00)00384-3