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 calcium-binding protein calretinin (CR) is present in a subpopulation of local-circuit neurons in the mammalian cerebral cortex containing gamma-aminobutyric acid. This light microscopic investigation provides a detailed qualitative and quantitative morphological analysis of CR-immunoreactive (CR+) neurons in the medial prefrontal cortex (mPFC; areas 24a,b,c, 32', and 25) of the normal adult human. The morphology of CR+ neurons and their areal and laminar distributions were consistent across human mPFC. The principal organisational features of CR+ labelling were the marked laminar distribution of immunoreactive somata and the predominantly vertical orientation of labelled axon-like and dendritic processes. Several types of CR- neurons were present in layer 1, including horizontally aligned Cajal-Retzius cells. In layers 2-6, CR+ neurons displayed a variety of morphologies: bipolar cells (49% of CR+ population), vertically bitufted cells (35%), and horizontally bitufted cells (3.5%). These neuron types were mainly located in layer 2/upper layer 3, and their dendritic processes were commonly aspiny and sometimes highly beaded. Aspiny (8%) and sparsely spiny multipolar (5%) CR+ neurons were also found. The mean somatic profile diameter of CR+ cells was 11.6 +/- 0.3 microm (mean +/- S.D). CA+ puncta formed pericellular baskets around unlabelled circular somatic profiles in layers 2/3 and around unlabelled pyramidal-shaped somata in layers 5/6. The somatic sizes of these unlabelled cell populations were significantly different. Immunolabelled puncta were also found in close contact with CR+ somata. Cortical depth distribution histograms and laminar thickness measurements defined the proportions of the overall CR- cell population in each layer: 7% in layer 1, 78% in layers 2/3, 14% in layers 5/6, and 1% in the white matter. In the tangential plane, CR+ neurons were distributed uniformly at all levels of the cortex. By using stereological counting procedures on immunoreacted Nissl-stained sections, CR+ neurons were estimated to constitute a mean 8.0% (7.2-8.7%) of the total neuron population in each cortical area. These data are compared with similar information obtained for the mPFC in monkey and rat (Gabbott and Bacon [1996b] J. Comp. Neurol. 364:657-608; Gabbott et al., [1997] J. Comp. Neurol. 377:465-499). This study provides important morphological insights into a neurochemically distinct subclass of local-circuit inhibitory neurons in the human mPFC.