This paper describes the quantitative areal and laminar distribution of identified neuron populations projecting from areas of prefrontal cortex (PFC) to subcortical autonomic, motor, and limbic sites in the rat. Injections of the retrograde pathway tracer wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) were made into dorsal/ventral striatum (DS/VS), basolateral amygdala (BLA), mediodorsal thalamus (MD), lateral hypothalamus (LH), mediolateral septum, dorsolateral periaqueductal gray, dorsal raphe, ventral tegmental area, parabrachial nucleus, nucleus tractus solitarius, rostral/caudal ventrolateral medulla, or thoracic spinal cord (SC). High-resolution flat-map density distributions of retrogradely labelled neurons indicated that specific PFC regions were differentially involved in the projections studied, with medial (m)PFC divided into dorsal and ventral sectors. The percentages that WGA-HRP retrogradely labelled neurons composed of the projection neurons in individual layers of infralimbic (IL; area 25) prelimbic (PL; area 32), and dorsal anterior cingulate (ACd; area 24b) cortices were calculated. Among layer 5 pyramidal cells, approximately 27.4% in IL/PL/ACd cortices projected to LH, 22.9% in IL/ventral PL to VS, 18.3% in ACd/dorsal PL to DS, and 8.1% in areas IL/PL to BLA; and 37% of layer 6 pyramidal cells in IL/PL/ACd projected to MD. Data for other projection pathways are given. Multiple dual retrograde fluorescent tracing studies indicated that moderate populations (<9%) of layer 5 mPFC neurons projected to LH/VS, LH/SC, or VS/BLA. The data provide new quantitative information concerning the density and distribution of neurons involved in identified projection pathways from defined areas of the rat PFC to specific subcortical targets involved in dynamic goal-directed behavior.

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The amygdala provides the medial prefrontal cortex (mPFC; areas 25, 32, and 24b) with salient emotional information. This study investigated the synaptic connectivity of identified amygdalocortical boutons (ACBs; labeled anterogradely following injections of Phaseolus vulgaris leucoagglutinin into the basolateral nucleus of the amygdala), with the dendritic processes of identified layer 5 corticospinal neurons in the rat mPFC. The corticospinal (CS) neurons in the mPFC had been retrogradely labeled with rhodamine fluorescent latex microspheres and subsequently intracellularly filled with biotinylated lucifer yellow to visualize their basal and apical dendrites. Two main classes of mPFC CS neurons were identified. Type 1 cells had apical dendrites bearing numerous dendritic spines with radiate basal dendritic arbors. Type 2 cells possessed apical dendrites with greatly reduced spine densities and a broad range of basal dendritic tree morphologies. Identified ACBs made asymmetric synaptic junctions with labeled dendritic spines and the labeled apical and basal dendritic shafts of identified CS neurons. On average, eight ACBs were closely associated with the labeled basal dendritic arbors of type 1 CS neurons and five ACBs with type 2 CS basal dendrites. The mean Scholl distance of ACBs from CS somata (for both types 1 and 2 cells) was 66 μm-coinciding with a region containing the highest length density of CS neuron basal dendrites. These results indicate that neurons in the BLA can monosynaptically influence CS neurons in the mPFC that project to autonomic regions of the thoracic spinal cord and probably to other additional subcortical target regions, such as the lateral hypothalamus.

The medial prefrontal cortex (mPFC) is directly involved in the integration of cognitive and autonomic functions underlying flexible goal-directed behavior (Cechetto and Saper, 1990;Neafsey et al., 1993;Loewy, 1991;Owens et al., 1999;Van Eden and Buijs, 2000;Drevets, 2000;Heidbreder and Groenewegen, 2003). In the rat, the mPFC is composed of the anterior cingulate (ACd, Brodmann area 24b), prelimbic (PL, area 32), infralimbic (IL, area 25), and peduncular (P) cortices (Neafsey et al., 1993;Gabbott et al., 2005;Resstel and Corrêa, 2006b).Anatomical and physiological evidence indicates that areas of dorsal (d) mPFC (ACd and dPL cortices) process cognitive information, whereas regions of ventromedial prefrontal cortex (vmPFC) (vPL, IL and P cortices) are also involved in autonomic and visceral functions, especially, cardiovascular and respiratory activities (Hardy and Mack, 1990;Neafsey, 1990;Loewy, 1991;Neafsey et al., 1993;Spyer, 1994;Fisk and Wyss, 2000;Uylings et al., 2003;Heidbreder and Groenewegen, 2003). Descending efferent projections from vmPFC, in particular IL cortex, innervate a wide range of subcortical autonomic centers, including the nucleus tractus solitarius (NTS) and ventrolateral medulla (VLM), brain stem nuclei strategically involved in cardiopulmonary activities (Agarwal and Calarescu, 1992;Van Giersbergen et al., 1992;Dampney, 1994;Owens and Verberne, 1996, 2000Owens et al., 1999). Indeed, stimulation of the vPL and IL cortices is known to influence arterial blood pressure and blood flow through specific vascular beds (Owens and Verberne, 2001). As a result, the vmPFC has been considered to represent a 'visceromotor' territory of the rodent PFC (Terreberry and Neafsey, 1987;Ruit and Neafsey, 1990;Loewy, 1991;Neafsey et al., 1993; Resstel and Corrêa, 2006a,b).Although the pathways from IL cortex to autonomic centers in the brain stem have been described in previous light microscope studies (Sesack et al., 1989;Hurley et al., 1991;Takagishi and Chiba, 1991;Van Eden and Buijs, 2000;Heidbreder and Groenewegen, 2003;Vertes, 2004;Gabbott et al., 2005), the ultrastructural identities and neurochemical content of the post-synaptic target neurons have not been investigated in detail (Zagon et al., 1994;Torrealba and Müller, 1999). Of specific functional significance is that catecholaminergic neurons in the NTS and rostral ventrolateral medulla (rVLM) are strategically in-*Correspondence to: P. L. A. Gabbott, Department of Biological Sciences, The Open University, Milton Keynes, MK7 6AA UK. Tel: ϩ44-1908-659469; fax: ϩ44-1908-654167. E-mail address: p.l.gabbott@open.ac.uk (P. L. A. Gabbott). Abbreviations: ACd, dorsal anterior cingulate cortex (area 24b); B, Bregma; BDA, biotinylated dextran amine; BLA, basolateral nucleus of the amygdala; CEA, central nucleus of the amygdala; DAB, 3,3=-diaminobenzidine; DMH, dorsomedial hypothalamic nucleus; DMX, dorsal motor nucleus of the vagus; IL, infralimbic cortex (area 25