There has never been a wholesale way of identifying neurons that are monosynaptically connected either to some other cell group or, especially, to a single cell. The best available tools, transsynaptic tracers, are unable to distinguish weak direct connections from strong indirect ones. Furthermore, no tracer has proven potent enough to label any connected neurons whatsoever when starting from a single cell. Here we present a transsynaptic tracer that crosses only one synaptic step, unambiguously identifying cells directly presynaptic to the starting population. Based on rabies virus, it is genetically targetable, allows high-level expression of any gene of interest in the synaptically coupled neurons, and robustly labels connections made to single cells. This technology should enable a far more detailed understanding of neural connectivity than has previously been possible.

The visual pulvinar is part of the dorsal thalamus, and in primates it is especially well developed. Recently, our understanding of how the visual pulvinar is subdivided into nuclei has greatly improved as a number of histological procedures have revealed marked architectonic differences within the pulvinar complex. At the same time, there have been unparalleled advances in understanding of how visual cortex of primates is subdivided into areas and how these areas interconnect. In addition, considerable evidence supports the view that the hierarchy of interconnected visual areas is divided into two major processing streams, a ventral stream for object vision, and a dorsal stream for visually guided actions. In this review, we present evidence that a subset of medial nuclei in the inferior pulvinar function predominantly as a subcortical component of the dorsal stream while the most lateral nucleus of the inferior pulvinar and the adjoining ventrolateral nucleus of the lateral pulvinar are more devoted to the ventral stream of cortical processing. These nuclei provide cortico-pulvinarcortical interactions that spread information across areas within streams, as well as information relayed from the superior colliculus via inferior pulvinar nuclei to largely dorsal stream areas.

Cortical computations critically involve local neuronal circuits. The computations are often invariant across a cortical area yet are carried out by networks that can vary widely within an area according to its functional architecture. Here we demonstrate a mechanism by which orientation selectivity is computed invariantly in cat primary visual cortex across an orientation preference map that provides a wide diversity of local circuits. Visually evoked excitatory and inhibitory synaptic conductances are balanced exquisitely in cortical neurons and thus keep the spike response sharply tuned at all map locations. This functional balance derives from spatially isotropic local connectivity of both excitatory and inhibitory cells. Modeling results demonstrate that such covariation is a signature of recurrent rather than purely feed-forward processing and that the observed isotropic local circuit is sufficient to generate invariant spike tuning.

The superior colliculus (SC) is the first station in a subcortical relay of retinal information to extrastriate visual cortex. Ascending SC projections pass through pulvinar and LGN on their way to cortex, but it is not clear how many synapses are required to complete these circuits or which cortical areas are involved. To examine this relay directly, we injected transynaptic rabies virus into several extrastriate visual areas. We observed disynaptically labeled cells in superficial, retino-recipient SC layers from injections in dorsal stream areas MT and V3, but not the earliest extrastriate area, V2, nor ventral stream area V4. This robust SC-dorsal stream pathway is most likely relayed through the inferior pulvinar and can provide magnocellular-like sensory inputs necessary for motion perception and the computation of orienting movements. Furthermore, by circumventing primary visual cortex, this pathway may also underlie the remaining visual capacities associated with blindsight.

Microelectrode mapping methods were used to define the parietal ventral somatosensory area (PV) on the upper bank of the lateral sulcus in five marmosets (Callithrix jacchus). In the same animals, neuroanatomical tracers were placed into electrophysiologically identified sites in PV and/or the second somatosensory area (S2). Foci of anterograde and retrograde label were related to electrophysiological maps of cortical areas and cortical and thalamic architecture. The results lead to the following conclusions: (1) Multiunit recordings from cortex on the upper bank of the lateral sulcus demonstrate that PV is somatotopically organized, with the face representation adjoining area 3b and the hindlimb and tail representations away from this border in cortex deep on the upper bank of the lateral sulcus. The forelimb representation is caudal in PV adjacent to the S2 forelimb representation. The body surface representation in PV approximates a mirror image of that in S2; (2) Areas PV and S2 are less myelinated and have less cytochrome oxidase enzyme activity than area 3b; (3) The ventroposterior inferior nucleus (VPI) of the thalamus provides the major somatosensory projections to PV. PV is reciprocally connected with VPI and anterior pulvinar; (4) PV has ipsilateral cortical connections with areas 3a, 3b, 1, and M1 and higher order somatosensory fields, and at least most of these connections are somatotopically matched; and (5) Callosal connections of PV are with S2 and PV of the other cerebral hemisphere. These results further establish PV as one of at least four somatosensory areas of the lateral sulcus of primates.

The existence of a third visual area, V3, along the outer margin of V2 was originally proposed for primates on the basis of projections from V1. The evidence for V3 was never totally convincing because investigators failed to demonstrate V1 projections to ventral V3, and projections to dorsal V3 could be attributed to the dorsomedial visual area (DM). We have reexamined the issue by placing large injections into both dorsal and ventral portions of V1 and subsequently processing flattened cortex for myelin and cytochrome oxidase so that borders of V1 and V2 could be determined accurately. The injections were in small-brained marmosets, where ventral V1 was most accessible and cortex could be flattened easily. The results indicate that dorsal V1 (representing the lower visual quadrant) projects to a narrow "dorsal V3" located between DM and dorsal V2, whereas ventral V1 (representing the upper visual quadrant) projects to a narrow "ventral V3." Architectonic borders for these dorsal and ventral strips were clearly apparent. In addition, all parts of V1 project to DM, whereas ventral V1 connections indicate that the dorsolateral area (DL) extends more ventral than has been established previously. We also placed injections within dorsal V2, dorsal and ventral DM, and dorsal, central, and ventral middle temporal (MT) area. Results from these injections were consistent with the proposed retinotopic organizations of V3, DM, and DL. We provide compelling evidence for the existence of areas V3, DM, and DL in marmosets and suggest that these areas are likely to be found in all primates.

Through more than 30 years of research, the nature of the third visual area, V3, and even its existence have been in question. Here, we used injections of up to five distinguishable tracers into both dorsal and ventral portions of V1 of macaque monkeys (representing the lower and upper visual quadrant, respectively) to provide compelling evidence for a V3 that is smaller than V2. This V3 includes both dorsal and ventral halves mirroring dorsal and ventral V2 in retinotopic organization. Of the approximately ten areas with V1 connections, V3 appears to account for about 20%.

Dorsal visual cortical areas are thought to be dominated by input from the magnocellular (M) visual pathway, with little or no parvocellular (P) contribution. These relationships are supported by a close correlation between the functional properties of these areas and the M pathway and by a lack of anatomical evidence for P input. Here we use rabies virus as a retrograde transynaptic tracer to show that the dorsal area MT receives strong input, via a single relay, from both M and P cells of the lateral geniculate nucleus. This surprising P input, likely relayed via layer 6 Meynert cells in primary visual cortex, can provide MT with sensitivity to a more complete range of spatial, temporal, and chromatic cues than the M pathway alone. These observations provide definitive evidence for P pathway input to MT and show that convergence of parallel visual pathways occurs in the dorsal stream.