Jonathan B. Levitt

Patterns of Intrinsic and Associational Circuitry in Monkey Prefrontal Cortex

Both local and long‐range connections are critical mediators of information processing in the cerebral cortex, but little is known about the relationships among these types of connections, especially in higher‐order cortical regions. We used quantitative reconstructions of the label arising from discrete (approximately 350 μm diameter) injections of biotinylated dextran amine and cholera toxin B to determine the spatial organization of the axon collaterals and principal axon projections furnished by pyramidal neurons in the supragranular layers of monkey prefrontal cortex (areas 9 and 46). Both terminals and cell bodies labeled by transport along axon collaterals in the gray matter formed intrinsic clusters which were arrayed as a series of discontinuous stripes of similar size and shape. The co‐registration of anterograde and retrograde transport confirmed that these convergent and divergent intrinsic connections also were reciprocal. Transport from the same injection sites along principal axons through the white matter formed associational clusters which were also arrayed as a series of discontinuous stripes. The dimensions of the anterogradely‐ and retrogradely‐labeled associational stripes were very similar to each other and to the intrinsic stripes. These findings demonstrate that divergence, convergence, and reciprocity characterize both the intrinsic and associational excitatory connections in the prefrontal cortex. These patterns of connections provide an anatomical substrate by which activation of a discrete group of neurons would lead to the recruitment of a specific neuronal network comprised of both local and distant groups of cells. Furthermore, the consistent size of the intrinsic and associational stripes (approximately 275 by 1,800 μm) suggests that they may represent basic functional units in the primate prefrontal cortex.

Independence and merger of thalamocortical channels within macaque monkey primary visual cortex: anatomy of interlaminar projections

An important issue in understanding the function of primary visual cortex in the macaque monkey is how the several efferent neuron groups projecting to extrastriate cortex acquire their different response properties. To assist our understanding of this issue, we have compared the anatomical distribution of V1 intrinsic relays that carry information derived from magno- (M) and parvocellular (P) divisions of the dorsal lateral geniculate nucleus between thalamic recipient neurons and interareal efferent neuron groups within area V1. We used small, iontophoretic injections of biocytin placed in individual cortical laminae of area V1 to trace orthograde and retrograde inter- and intralaminar projections. In either the same or adjacent sections, the tissue was reacted for cytochrome oxidase (CO), which provides important landmarks for different efferent neuron populations located in CO rich blobs and CO poor interblobs in laminae 2/3, as well as defining clear boundaries for the populations of efferent neurons in laminae 4A and 4B. This study shows that the interblobs, but not the blobs, receive direct input from thalamic recipient 4C neurons; the interblobs receive relays from mid 4C neurons (believed to receive convergent M and P inputs), while blobs receive indirect inputs from either M or P (or both) pathways through layers 4B (which receives M relays from layer 4C alpha) and 4A (which receives P relays directly from the thalamus as well as from layer 4C beta). The property of orientation selectivity, most prominent in the interblob regions and in layer 4B, may have a common origin from oriented lateral projections made by mid 4C spiny stellate neurons. While layer 4B efferents may emphasize M characteristics and layer 4A efferents emphasize P characteristics, the dendrites of their constituent pyramidal neurons may provide anatomical access to the other channel since both blob and interblob regions in layers 2/3 have anatomical access to M and P driven relays, despite functional differences in the way these properties may be expressed in the two compartments.

Connections between the pulvinar complex and cytochrome oxidase-defined compartments in visual area V2 of macaque monkey

We examined the distribution of pulvinar afferents to visual area V2 of macaque monkey cerebral cortex in relation to the distribution of the metabolic enzyme cytochrome oxidase (CO). V2 contains three sets of stripelike subregions that are marked by differential staining for CO, and which have different corticocortical connections. The pulvinar provides the major subcortical input to V2, and this input is known to be patchy. We were interested to determine how the pattern of pulvinar afferents relates to the layout of the three stripelike compartments that characterize V2. We made large injections of WGA-HRP into the pulvinar (labelling both the inferior and lateral divisions) and mapped the resulting orthograde terminal and retrograde cell label within V2. We observed pulvinar terminal label mainly in lower layer 3 (at the layer 4 border), with light label in layer 1 as well; terminal label in layers 3–4 was distributed in discrete patches with faint bridges of light label between. Comparison with adjacent sections stained for CO or Cat-301 showed that pulvinar terminal zones aligned precisely with regions of increased CO staining, and targeted both “thick” (Cat-301+) and “thin” CO-rich stripes, avoiding the pale stripes (which aligned with the faint bridges of terminal label). Retrogradely labelled cells were found in layers 5A and 6, but the bulk of the feedback to pulvinar arose from layer 6 rather than layer 5 (unlike V1, where feedback to pulvinar arises primarily from layer 5B). These results show that the increased CO staining in certain subregions of V2 is closely correlated with the presence of thalamic terminals from the pulvinar. Although we cannot rule out the possibility that different sets of pulvinar neurons project to different CO compartments in V2, the presence of a prominent thalamic input shared by the “thick” and “thin” CO stripes (which receive different V1 afferents and make different feedforward projections to other visual cortical areas) could underlie the preferential intrinsic interconnections shown to exist between these V2 subregions and suggests another potential source of integration between the two cortical visual streams.

Substrates for Interlaminar Connections in Area V1 of Macaque Monkey Cerebral Cortex

On the basis of our earlier studies of macaque visual cortical area V1 (Lund, 1973; Blasdel et al., 1985; Fitzpatrick et al., 1985) using Golgi impregnations and small intralaminar injections of horseradish peroxidase (HRP), a schema (reproduced here in Fig. 1) was outlined for spiny stellate neuron relays out of the thalamic recipient divisions of layer 4C (Lund, 1990). This diagram illustrates the finding that although the thalamic axons from magnocellular and parvocellular divisions of the lateral geniculate nucleus (LGN) terminate in the α and β divisions respectively of layer 4C (Hubel and Wiesel, 1972; Blasdel and Lund, 1983), the relays out of layer 4C seemed to fall into three sets. The lowermost set seemed to project in a very narrowly focused fashion to layer 4A and lower layer 3B, a set in the middle depth of layer 4C seemed to project to Open image in new window Figure 1. Diagram summarizing current information concerning the laminar distribution of thalamic inputs (to the left of diagram) from the lateral geniculate nucleus (LGN) to cortical area V1 in the macaque, and their further relays by thalamic recipient spiny stellate neurons of layer 4C. Thalamic axons P1 (to layer 4Cβ) and P2 (to layer 4A) appear to arise from different thalamic neuron populations, both situated in the LGN parvocellular laminae (Fitzpatrick et al., 1983; Blasdel and Lund, 1983). Thalamic axons M1 (to upper 4Cα) and M2 (terminals throughout 4Cα) arise from the magnocellular laminae of the LGN; axon population I, relaying to the upper layer blobs, comes from the intercalated layers of the LGN (Hendrickson et al., 1978; Fitzpatrick et al., 1983). The output from layer 4C is suggested to be a gradient, created by dendritic sampling of both parvocellular and magnocellular inputs by the postsynaptic spiny stellate neurons; 4C neurons are suggested to shift their projection target from layers 4A–3B to layer 4B as their primary LGN input shifts from the parvocellular layers to the magnocellular layers. (See Lund, 1990, for further discussion.) Diagram modified from Lund (1990) with permission. both layers 3B and 4B with more spreading axon arbors, and an upper set seemed to project principally to layer 4B. It was suggested that this distribution of projections could derive from a gradient of sampling of the magnocellular and parvocellular afferents by continuously overlapped dendritic fields of spiny stellate neurons through the depth of layer 4C; the three efferent sets of cells in layer 4C were seen as partially overlapping in depth.