NEUROSYSTEMS Thalamic projections to the macaque caudal ventrolateral prefrontal areas 45A and 45B Massimo Contini, 1 Matteo Baccarini, 2,3 Elena Borra, 2 Marzio Gerbella, 2 Stefano Rozzi 2 and Giuseppe Luppino 2 1 Dipartimento di Scienze Fisiologiche, Universita ` di Firenze, Firenze, Italy 2 Dipartimento di Neuroscienze, Sezione di Fisiologia, Universita ` di Parma, Istituto Italiano di Tecnologia (IIT, Unita ` di Parma), I-43100 Parma, Italy 3 Dipartimento di Scienze Umane, Universita ` di Ferrara, Ferrara, Italy Keywords: Broca’s region, frontal eye field, mediodorsal nucleus, prefrontal cortex, thalamus Abstract We studied the sources of thalamic projections to the caudal ventrolateral prefrontal areas 45A and 45B, which display markedly distinct cortical connections [M. Gerbella et al. (2010) Cereb. Cortex, 20, 141–168], and compared them with those to area 8 ⁄ FEF (frontal eye field). Both areas 45A and 45B were the targets of highly predominant projections from the mediodorsal nucleus (MD) and of additional projections, mostly from the magnocellular ventral anterior and the medial pulvinar nucleus. The projection profiles from different MD subdivisions clearly distinguished these two areas from one another and from area 8 ⁄ FEF. Area 45A was the target of predominant projections from parvicellular MD and of minor, albeit robust, projections from magnocellular MD. The opposite was true for area 45B: magnocellular MD was the major source of projections and parvicellular MD contributed minor, albeit robust, projections. Furthermore, area 45B, but not area 45A, was targeted by robust projections from multiform MD, the principal thalamic nucleus for area 8 ⁄ FEF. These results provide further evidence for the distinctiveness of areas 45A and 45B, and support the idea that area 45B is affiliated with the frontal oculomotor system, challenging the proposed homology of this area with part of the human language-related area 45 (rostral part of Broca’s region). Furthermore, the present data provide evidence for potentially robust trans- thalamic (via magnocellular MD) afferent, as well as direct and reciprocal, amygdaloid connections of areas 45A and 45B, suggesting the contribution of emotional information to the differential role of these two areas in non-spatial information processing. Introduction The macaque area 45 was defined by Petrides & Pandya (1994, 2002) as a caudal ventrolateral prefrontal (VLPF) area formed by two slightly different architectonic sectors: a caudal one (45B) lying in the anterior bank of the inferior arcuate sulcus, ventral to the frontal eye field (FEF), architectonically and ⁄ or functionally defined (Bruce et al., 1985; Huerta et al., 1987; Stanton et al., 1989), and a rostral one (45A) located on the rostrally adjacent inferior frontal convexity. Petrides & Pandya (2002, 2009) also showed that area 45, as a whole, is connected to several cortical areas, including auditory-related and multisensory areas of the superior temporal gyrus and caudal areas of the inferior parietal lobule. Based on these data and on comparative cytoarchitectonic criteria, they proposed that area 45 is the homolog of the corresponding language-related area of the human brain. The finding that the caudal VLPF hosts neurons involved in the control of communicative behavior (see Romanski & Averbeck, 2009) supported this hypothesis. However, recent evidence showed that 45A and 45B are two architectonically different areas that display connectivity patterns clearly distinguishing them from one another and from their neighboring areas (Gerbella et al., 2007, 2010). These data suggested that 45A and 45B are two distinct cortical entities, possibly playing a differential role in non-spatial information processing: area 45A corresponds to the prefrontal sector for which a role in communication behavior was proposed; whereas area 45B is a distinct prearcuate area, possibly affiliated with the oculomotor frontal system. In the present study, we sought to define the sources of thalamic projections to areas 45A and 45B. It is well-established that the mediodorsal nucleus (MD) is the major source of thalamo-prefrontal projections, and consists of distinct subdivisions provided with unique profiles of subcortical afferents and topographically organized connections with prefrontal and non-prefrontal areas (e.g. Kievit & Kuypers, 1977; Goldman-Rakic & Porrino, 1985; Ilinsky et al., 1985; Russchen et al., 1987; Darian-Smith et al., 1990; Barbas et al., 1991; Ray & Price, 1993; Matelli & Luppino, 1996; Rouiller et al., 1999; Erickson & Lewis, 2004; Erickson et al., 2004; Xiao et al., 2009). These projections, as well as those from other thalamic nuclei, might have a dual functional role: (i) to relay specific subcortical outputs to specific cortical sectors or areas; and (ii) to mediate trans-thalamic information flow between different cortical areas (e.g. McFarland & Haber, 2002; Sherman, 2007; Cappe et al., 2009; Xiao et al., 2009). Thus, information on the thalamic projections to areas 45A and 45B would extend our knowledge on the connectivity of these two areas, Correspondence: Prof Giuseppe Luppino, as above. E-mail: luppino@unipr.it Received 25 March 2010, revised 16 June 2010, accepted 29 June 2010 European Journal of Neuroscience, Vol. 32, pp. 1337–1353, 2010 doi:10.1111/j.1460-9568.2010.07390.x ª 2010 The Authors. European Journal of Neuroscience ª 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd European Journal of Neuroscience