Charles G. Gross

Neurogenesis in the adult brain: death of a dogma

For over 100 years a central assumption in the field of neuroscience has been that new neurons are not added to the adult mammalian brain. This perspective examines the origins of this dogma, its perseverance in the face of contradictory evidence, and its final collapse. The acceptance of adult neurogenesis may be part of a contemporary paradigm shift in our view of the plasticity and stability of the adult brain.

Visuotopic Organization and Extent of V3 and V4 of the Macaque

The representation of the visual field in areas V3 and V4 of the macaque was mapped with multiunit electrodes. Twelve Macaca fascicularis were studied in repeated recording sessions while immobilized and anesthetized. V3 is a narrow strip (4–5 mm wide) of myeloarchitectonically distinct cortex located immediately anterior to V2. It contains a systematic representation of the central 35–40 degrees of the contralateral visual field; the representation of the upper quadrant is located ventrally in the hemisphere and that of the lower quadrant, dorsally. There is a small gap between the dorsal (V3d) and ventral (V3v) portions of V3. The representation of the horizontal meridian is adjacent to that in V2 and forms the posterior border of both V3d and V3v. Most or all of the anterior border of V3d consists of the representation of the lower vertical meridian. The entire anterior border of V3v consists of the representation of the upper vertical meridian. V4 is a strip of myeloarchitectonically distinct cortex 5–8 mm wide, immediately anterior to V3. It contains a coarse, but systematic, representation of approximately the central 35–40 degrees of the contralateral visual field. The representation of the upper visual field is located ventrally in the hemisphere. Most of the representation of the lower visual field is located dorsally. The posterior border of V4 corresponds to the representation of the vertical meridian, and the representation of the horizontal meridian is located at or near its anterior border. In both V3 and V4, the representation of the central visual field is magnified relative to that of the periphery. In both areas, the size of receptive fields increases with increasing eccentricity; however, at a given eccentricity, the receptive fields of V4 are larger than those of V3.

Visual areas in the temporal cortex of the macaque.

Visual receptive fields and responsiveness of neurons to somesthetic and auditory stimuli were studied in the inferior temporal cortex and adjacent regions of immobilized macaques. Neurons throughout cytoarchitectonic area TE were responsive only to visual stimuli and had large receptive fields that almost always included the center of gaze and usually extended into both visual half-fields. There was no indication of any visuotopic organization within area TE. Neurons in an anterior and in a dorsal portion of TE tended to have larger receptive fields. By contrast, dorsal, ventral and anterior to area TE, units often responded to somesthetic and auditory as well as to visual stimuli. In these regions visual receptive fields were even larger than in TE and often included the entire visual field. Posterior to TE the neurons were exclusively visual and had much smaller receptive fields that were confined to the contralateral visual field and were topographically organized.

Adult-generated hippocampal and neocortical neurons in macaques have a transient existence

Previously we reported that new neurons are added to the hippocampus and neocortex of adult macaque monkeys. Here we compare the production and survival of adult-generated neurons and glia in the dentate gyrus, prefrontal cortex, and inferior temporal cortex. Twelve adult macaques were injected with the thymidine analogue BrdUrd, and the phenotypes of labeled cells were examined after 2 h, 24 h, 2 wk, 5 wk, 9 wk, and 12 wk by using the following immunocytochemical markers: for immature and mature neurons, class III β-tubulin (TuJ1); for mature neurons, neuronal nuclei; for astrocytes, glial fibrillary acidic protein; and for oligodendrocytes, 2′,3′-cyclic nucleotide 3′ phosphodiesterase. We found that the dentate gyrus had many more BrdUrd-labeled cells than either neocortical area. Furthermore, a greater percentage of BrdUrd-labeled cells expressed a neuronal marker in the dentate gyrus than in either neocortical area. The number of new cells in all three areas declined by 9 wk after BrdUrd labeling, suggesting that some of the new cells have a transient existence. BrdUrd-labeled cells also were found in the subventricular zone and in the white matter between the lateral ventricle and neocortex; some of the latter cells were double-labeled for BrdUrd and TuJ1. Adult neocortical neurogenesis is not restricted to primates. Five adult rats were injected with BrdUrd, and after a 3-wk survival time, there were cells double-labeled for BrdUrd and either TuJ1 or neuronal nuclei in the anterior neocortex as well as the dentate gyrus.

Quantitative investigation of connections of the prefrontal cortex in the human and macaque using probabilistic diffusion tractography

The functions of prefrontal cortex (PFC) areas are constrained by their anatomical connections. There is little quantitative information about human PFC connections, and, instead, our knowledge of primate PFC connections is derived from tracing studies in macaques. The connections of subcortical areas, in which white matter penetration and hence diffusion anisotropy are greatest, can be studied with diffusion-weighted imaging (DWI) tractography. We therefore used DWI tractography in four macaque and 10 human hemispheres to compare the connections of PFC regions with nine subcortical regions, including several fascicles and several subcortical nuclei. A distinct connection pattern was identified for each PFC and each subcortical region. Because some of the fascicles contained connections with posterior cortical areas, it was also possible to draw inferences about PFC connection patterns with posterior cortical areas. Notably, it was possible to identify similar circuits centered on comparable PFC regions in both species; PFC regions probably engage in similar patterns of regionally specific functional interaction with other brain areas in both species. In the case of one area traditionally assigned to the human PFC, the pars opercularis, the distribution of connections was not reminiscent of any macaque PFC region but, instead, resembled the pattern for macaque ventral premotor area. Some limitations to the DWI approach were apparent; the high diffusion anisotropy in the corpus callosum made it difficult to compare connection probability values in the adjacent cingulate region.

Visual Receptive Fields of Neurons in Inferotemporal Cortex of the Monkey

Neurons in inferotemporal cortex (area TE) of the monkey had visual receptive fields which were very large (greater than 10 by 10 degrees) and almost always included the fovea. Some extended well into both halves of the visual field, while others were confined to the ipsilateral or contralateral side. These neurons were differentially sensitive to several of the following dimensions of the stimulus: size and shape, color, orientation, and direction of movement.

Spatial maps for the control of movement

Neurons in the ventral premotor cortex of the monkey encode the locations of visual, tactile, auditory and remembered stimuli. Some of these neurons encode the locations of stimuli with respect to the arm, and may be useful for guiding movements of the arm. Others encode the locations of stimuli with respect to the head, and may be useful for guiding movements of the head. We suggest that a general principle of sensory-motor integration is that the space surrounding the body is represented in body-part-centered coordinates. That is, there are multiple coordinate systems used to guide movement, each one attached to a different part of the body. This and other recent evidence from both monkeys and humans suggest that the formation of spatial maps in the brain and the guidance of limb and body movements do not proceed in separate stages but are closely integrated in both the parietal and frontal lobes.

Effects of foveal prestriate and inferotemporal lesions on visual discrimination by rhesus monkeys

SummaryAblation of inferotemporal cortex in monkeys impairs visual discrimination learning, and inferotemporal cortex receives visual information from striate cortex by way of the circumstriate belt. Yet most previous studies have failed to find any discrimination impairment after partial ablations of the circumstriate belt.In this experiment severe impairments in post-operative acquisition and retention of visual discrimination problems were found after lesions of “foveal prestriate cortex”, i.e. the portion of the circumstriate belt which receives a projection from the cortical representation of the fovea in striate cortex and which lies, largely buried, in the ventrolateral portion of prestriate cortex. Although foveal prestriate lesions produced a greater impairment on individual pattern discrimination tasks than inferotemporal lesions, the opposite was true of concurrent visual discrimination tasks in which several different pairs of discriminanda are presented in each testing session until the animal learns to discriminate every pair.The results are related to a two-stage model of discrimination learning and it is suggested that foveal prestriate lesions impair visual attention or perception, whereas inferotemporal lesions disturb the associative or mnemonic stage of visual discrimination learning.

A bimodal map of space: somatosensory receptive fields in the macaque putamen with corresponding visual receptive fields

The macaque putamen contains neurons that respond to somatosensory stimuli such as light touch, joint movement, or deep muscle pressure. Their receptive fields are arranged to form a map of the body. In the face and arm region of this somatotopic map we found neurons that responded to visual stimuli. Some neurons were bimodal, responding to both visual and somatosensory stimuli, while others were purely visual, or purely somatosensory. The bimodal neurons usually responded to light cutaneous stimulation, rather than to joint movement or deep muscle pressure. They responded to visual stimuli near their tactile receptive field and were not selective for the shape or the color of the stimuli. For cells with tactile receptive fields on the face, the visual receptive field subtended a solid angle extending from the tactile receptive field to about 10 cm. For cells with tactile receptive fields on the arm, the visual receptive field often extended further from the animal. These bimodal properties provide a map of the visual space that immediately surrounds the monkey. The map is organized somatotopically, that is, by body part, rather than retinotopical ly as in most visual areas. It could function to guide movements in the animals immediate vicinity. Cortical areas 6, 7b, and VIP contain bimodal cells with very similar properties to those in the putamen. We suggest that the bimodal cells in area 6, 7b, VIP, and the putamen form part of an interconnected system that represents extrapersonal space in a somatotopic fashion.

Visual Functions of Inferotemporal Cortex

Traditionally, the cerebral cortex on the inferior surface of the temporal lobe was considered part of the “silent” or “association” areas of the brain. The term “association cortex” was first used by Flechsig [63] to describe cortical regions that became myelinated relatively late. He thought that “association” among the senses occurred here. In subsequent decades association cortex became the presumed site of “association of ideas” and then of association or linkage between stimuli and responses in learning.