A Numerical Analysis of the Geniculocortical Input to Striate Cortex in the Monkey

Using data that are available in various publications, a quantitativeanalysis has been made of the geniculocortical input to layerIVC of the macaque striate cortex. The data suggest that only1.3–1.9% of the excitatory, or asymmetric synapses inlayer IVC     

Direct Temporal-Occipital Feedback Connections to Striate Cortex (V1) in the Macaque Monkey

Although there have been reports of sparse projections fromtemporal areas TE, TF, and even TH to area V1, it is generallybelieved that cortical afferents to V1 originate exclusivelyfrom prestriate areas. Injections of anterograde tracers inanterior occipital and temporal areas, however, consistentlyproduce labeled terminals in area V1. In order to confirm theseresults and display the full range of foci projecting to V1,we injected V1 in two monkeys with the retrograde tracer fastblue. Feedback connections were found, as expected, from severalprestriate areas (V2, V3, V4, and MT). These originate fromneurons in layers 3A and 6. Connections were also found fromseveral more distal regions, namely, areas TEO, TE, TF, TH,and from cortex in the occipitotemporal and superior temporal(STS) sulci. Filled neurons occurred in two small foci in thecaudal intraparietal sulcus. These more distal feedback connectionstend to originate only from layer 6. An additional injectionof the retrograde tracer diamidino yellow in area V2 of oneanimal revealed a similarly widespread network of feedback connections.In some areas (In the STS and in TEO), 10–15% of fluorescentneurons were double-labeled. These results indicate that feedback connections to early visualcortex derive from a widespread network of areas, includinglimbic-associated cortices. These connectional patterns testifyto the massive recursiveness of anatomical pathways. As thereare no reports of projections from V1 to anterior temporal cortices,our results also indicate that some cortical feedback connectionsmay not be strictly reciprocal.     

Laminar and Columnar Organization of Immunoreactivity for Calcineurin, a Calcium- and Calmodulin-regulated Protein Phosphatase, in Monkey Striate Cortex

Protein phosphorylation and dephosphorylation play an importantrole in neuronal signal transduction. In this study the distributionof calcineurin, a calcium/calmodulin-dependent protein phosphatase,was investigated in the striate cortex of two Old World monkeys,Macaca fascicularis and Papio anubis, using a well-characterized,affinity-purified polyclonal antibody to calcineurin. In orderto relate the calcineurin distributions to established cytochemicalmarkers, adjacent sections were processed for the visualizationof cytochrome oxidase. The staining patterns obtained from thetwo species were remarkably similar. The results indicate that(1) monkey striate cortex exhibits strong calcineurinlike immunoreactivitythat is present both in the neuropil and in neurons, most ofwhich have characteristics of pyramidal cells; (2) the distributionof calcineurin is laminar specific; and (3) it is complementaryto that of cytochrome oxidase activity with respect to bothits laminar and its tangential pattern. In sections perpendicularto the cortical lamination calcineurin immunoreactivity is highin layers II and III, reduced in layer IVA, nearly as denseas in supragranular layers in layer IVB, minimal in layer IVC,and again enhanced, but not as much as in supragranular layers,in layers V and VI. In addition to these lamina-specific variations,the density of calcineurin-like immunoreactivity exhibits aperiodic modulation along trajectories parallel to the pialsurface that is most marked in layer III but also discernablein infragranular layers. Accordingly, in tangential sectionsthrough supragranular layers the calcineurin distribution ismosaic-like with patches of high density corresponding to cytochromepoorregions (interblob regions) and zones of low density correspondingto areas of high cytochrome oxidase activity (blobs).     

Relation between Patterns of Intrinsic Lateral Connectivity, Ocular Dominance, and Cytochrome Oxidase-Reactive Regions in Macaque Monkey Striate Cortex

To help understand the role of long-range, clustered lateralconnections in the superficial layers of macaque striate cortex(area V1), we have examined the relationship of the patternsof intrinsic connections to cytochrome oxidase (CO) blobs, interblobs,and ocular dominance (OD) bands, using biocytin based neuroanatomicaltracing, CO histochemistry, and optical imaging. Microinjectionsof biocytin in layer 3 resulted in an asymmetric field (averageanisotropy of 1.8; maximum spread—3.7 mm) of labeled axonterminal clusters in layers 1–3, with the longer axisof the label spread oriented orthogonal to the rows of blobsand imaged OD stripes, parallel to the V1/V2 border. These labeledterminal patches (n = 186) from either blob or interblob injections(n = 20) revealed a 71% (132 out of 186) commitment of patchesto the same compartment as the injection site; 11% (20 out of186) to the opposite compartment, and 18% (34 out of 186) toborders of blob-interblob compartments, indicating that theconnectivity pattern is not strictly blob to blob, or interblobto interblob (p < 0.005; $$$²) In injections placed withinsingle OD domains (n = 11), 54% of the resulting labeled terminalpatches (43 out of 79) fell into the same OD territories asthe injection sites, 28% (22 out of 79) into the opposite ODregions, and 18% (14 out of 79) on borders, showing some connectionalbias toward same-eye compartments (p < 0.02; ANOVA). Individualinjection cases, however, varied in the degree (50–100%for CO patterns, 22–100% for 0D patterns) to which theyshowed same-compartment connectivity. These results reveal thatwhile connectivity between similar compartments predominates(e.g., blob to blob, right eye column to right eye column),interactions do occur between functionally different regions.     

Prenatal Development of Parvalbumin Immunoreactivity in the Human Striate Cortex

In human primary visual cortex, parvalbumin (PV) is expressedby Cajal-Retzius cells in layer I by 20 weeks of gestation (20W),but its immunoreactivity is mostly lost by term. PV immunoreactivityin layers II–VI mainly develops later, from 26 to 34W,following an approximately ‘inside-outside’ sequencein a series of bands. PV-positive perikarya appear in layerV by 20W, but only in small numbers. They increase in numberand staining intensity by 26W. By 30W a band of densely labelledsomata and neuropil occupies layers IVC–VI. By 34W a second,less dense, band of cell bodies and neuropil appears in IVBand IVC     

Development of Inferior Temporal Cortex in the Monkey

Inferior temporal (IT) cortex is critical for visual patternrecognition in adult primates. However, the functional developmentof IT cortex appears to be incomplete until late in the firstyear of life in monkeys and probably beyond. Responses of neuronsin IT are substantially weaker, of longer latency, and moresusceptible to anesthesia within at least the first half yearof life. In addition, refinement of connections of IT, particularlythose with regions in the opposite hemisphere and with regionsrelated to memory and attention, continues for at least severalmonths after birth. Moreover, many of the pattern recognitionfunctions that IT supports in adulthood themselves show a veryprotracted period of development, and damage to IT cortex ininfancy appears to have relatively little effect on patternrecognition abilities, despite the pronounced effects of comparabledamage in adulthood. These findings all suggest that IT undergoesan extended period of postnatal development, during which bothvisual experience and the maturation of other brain structuresmay contribute to the emergence of mechanisms of pattern recognitionwithin IT. In other respects, fundamental characteristics of IT emergequite early. For example, despite their weaker responses, ITneurons have adult-like patterns of responsiveness—includingpronounced form selectivity and large bilateral receptive fields—asearly as we were able to test (     

Mechanisms of Stereopsis in Monkey Visual Cortex

A substantial proportion of neurons in the striate and prestriatecortex of monkeys have stereoscopic properties; that is, theyrespond differentially to binocular stimuli that are known inhumans to provide cues for stereoscopic depth perception. Stereoscopicneurons, as these cells may be called, are selective for horizontalpositional disparity (i.e., display disparity selectivity) andfor the textural correlation between images over their receptivefields (i.e., they show correlation selectivity). Many neuronshave tuned disparity response profiles that collectively coverthe entire range of physiological disparities. Neurons withpeak responses at or about the zero disparity ("tuned zero neurons,"excitatory or inhibitory) have narrow and symmetrical profiles.Neurons that are tuned to larger disparities, either crossed("tuned near neurons") or uncrossed ("tuned far neurons"), havebroader excitatory profiles that are asymmetrically wider towardthe smaller disparities, and commonly include an inhibitorycomponent about the zero disparity. Other stereoscopic neuronshave reciprocal profiles ("near" or "far" neurons, respectively)in the sense that they respond with excitation to crossed oruncrossed disparities, and with suppression to disparities ofopposite sign. Stereoscopic neurons can also signal the texturalcorrelation between paired retinal images by giving differentresponses to random-dot patterns that have, and to those thatdo not have, the same dot distribution over the neuron's leftand right receptive fields. Tuned-zero excitatory neurons characteristicallyrespond to uncorrelation with suppression; tuned-zero inhibitoryneurons, with excitation; and both types give the opposite responsesto correlated stereopatterns. Neurons selective for nonzerodisparities, both tuned and reciprocal, also give excitatoryresponses to uncorrelated stimuli, but these responses are smallerand more variable than those evoked by correlated patterns atthe effective disparities. These findings suggest that stereoscopicneurons in the visual cortex of the macaque comprise three operationalsystems: (1) a zero-disparity system that is involved in finedepth discrimination with the obligatory singleness of vision,and the maintenance of vergence; and (2) a near-, and (3) afar-disparity system that together signal qualitative estimatesof depth with double vision, and vergence responses to largedisparities.     

Postnatal Maturation of the Direct Corticospinal Projections in the Macaque Monkey

Postnatal changes in the topography of the multiple corticospinalprojections in the macaque monkey were followed using retrogradelytransported fluorescent tracers, and related to the monkey'sacquisition of manual dexterity; both behavioral and anatomicalmaturation were completed by about 8 postnatal months. Cortical origins of the corticospinal projections were examinedby constructing planar projection maps of the distributionsof labeled corticospinal neuron somas; these somas were foundonly in lamina V. At birth elaborate somatotopically organizedcorticospinal projections from primary motor cortex (area 4),the mesial supplementary motor area and cingulate areas 23 and24, area 12, dorsolateral area 6aß, the dorsolateraland ventral area 6e     

The Functional Organization of Local Circuits in Visual Cortex: Insights from the Study of Tree Shrew Striate Cortex

We have used a combination of anatomical and physiological techniquesto explore the functional organization of vertical and horizontalconnections in tree shrew striate cortex. Our studies of verticalconnections reveal a remarkable specificity in the laminar arrangementof the projections from layer IV to layer III that establishesthree parallel intracortical pathways. The pathways that emergefrom layer IV are not simple continuations of parallel thalamocorticalpathways. Layer IV and its connections with layer II/III restructurethe inputs from the LGN, combining the activity from ON andOFF channels and from the left and right eye and transmit theproducts of this synthesis to separate strata within the overlyinglayers. In addition, studies of two other prominent verticalconnection pathways, the projections from layer VI to layerIV and from layer II/III to layer V suggest that the parallelnature of these systems is perpetuated throughout the corticaldepth. Our studies of horizontal connections have revealed a systematicrelationship between a neuron's orientation preference and thedistribution of its axon arbor across the cortical map of visualspace. Horizontal connections in layer II/III extend for greaterdistances and give rise to a greater number of terminals alongan axis of the visual field map that corresponds to the neuron'spreferred orientation. These findings suggest that the contributionof horizontal inputs to the response properties of layer II/IIIneurons is likely to be greater in regions of visual space thatlie along the axis of preferred orientation (endzones) thanalong the orthogonal axis (side zones). Topographically alignedhorizontal connections may contribute to the orientation preferenceof layer II/III neurons and could account for the axial specificityof some receptive field surround effects. Together, these results emphasize that specificity in the spatialarrangement of local circuit axon arbors plays an importantrole in shaping the response properties of neurons in visualcortex.     

Minicolumnar Activation Patterns in Cat and Monkey SI Cortex

The distribution of stimulus-evoked ¹⁴C-2-deoxyglucose (2DG)labeling in primary somatosensory cortex (SI) of monkey (Macacafasciculans) and cat was investigated. Reconstructions of theglobal pattern of labeling reveal that discrete skin stimulievoke activity within an extensive region of SI, and that theactivation pattern typically consists of multiple, elongatedregions of above-background labeling ("modules," typically 0.5–1.0mm wide, and 1–4 mm long). Evidence obtained using recentlydeveloped methods (Tommerdahl, 1989) for quantitative analysisof 2DG activity patterns is shown to be consistent with theidea (Whitsel et al., 1991) that SI modules typically are boundedby zones dominated by stimulus-evoked inhibition. The labelingpat tern within individual 2DG modules In SI of both cats andmonkeys is analyzed quantitatively (in the frequency domain).Within-module spatial activation patterns are demonstrated tohe periodic, consisting of radially on ent.d profiles of above-backgroundlabeling separated from each other by less strongly labeledradial profiles. The spectral characteristics of within-module2DG la beling change systematically with location along themodule's long axis: spatial frequencies htween 18 and 35 cycles/mmare prominent in the labeling that oc cupies both the middleand upper layers at central locations in the module, but area less obvious component of the labeling in both the middleand upper layers at locations remote to the module center. Sincethe radially oriented periodic variation both (1) in 2DG labelingin regions of SI outside modules and (2) in optical densityin images of Nissl-stained sections of SI consists pre dominantlyof spatial frequencies in the range of 18–35 cycles/mm,it is concluded that the radial profiles of labeling withinindividual 2DG modules correspond to groupings of minicolumnadistinguishable from their neighbors on the basis of labelingintensity. The findings raise the possibility that highly structured,within-mod ule spatial patterns of SI minicolumnar activationen code information about the physical properties of tactilestimuli.     

Information Cascade from Primary Auditory Cortex to the Amygdala: Corticocortical and Corticoamygdaloid Projections of Temporal Cortex in the Rat

Corticocortical and corticoamygdaloid connections of temporalcortext and perirhinal cortex (PRh) were examined in the ratwith the anterograde tracer Phaseolus vulgaris leucoagglutinin(PHA-L). lontophoretic injections of PHA-L into area TE1 resultedin columnar axonal terminations in surrounding and contralateralregions of temporal neocortex and in the striatum, but not inthe amygdala. Within temporal neocortex, labeled fibers werepresent locally in adjacent regions of TE1, as well as in TE2d,TE1v, TE3v, and TE2c. Injection of cortical areas TE1v, TE3v,and TE2c, which received projections from TE1, or injectionsof perirhinal periallocortex, which received projections fromTE1v, TE2v, and TE3v, resulted in projections to the amygdala.The pattern of corticocortical and corticoamygdaloid projectionsdiffered among the divisions of auditory cortex. TE1 exhibitedextensive ipsilateral and contralateral projections to temporalcortical regions and no projections to the amygdala. In contrast,areas of temporal neocortex ventral and posterior to TE1, includingTE1v, TE3v, TE2c, and PRh, had more limited ipsi- and contralateralcorticocortical projections but had an increased connectivitywith the subcortical forebrain, especially the lateral nucleusof the amygdala (AL). There was a topographic organization tothe AL afferents. The dorsal subdivision of AL received projectionsfrom TE1v, TE3v, TE2c, and PRh, while the ventrolateral divisionreceived projections from TE3v, TE2c, and PRh. The ventromedialdivision received projections only from PRh, which, unlike othertemporal cortical areas, also projected to the ba-solateraland basomedial nuclei of the amygdala. These findings definethe complete sequence of connections linking primary auditorycortex with the amygdala in the rat. In addition, the findingsindicate that the ventral portion of TE1, designated TE1v, hasconnections that distinguish it from dorsal TE1, namely, denseprojections to AL and a diminished number of corticocorticalprojections ipsilaterally and contralaterally. Finally, theresults suggest a topographic organization to the cortical terminationswithin the amygdala.     

Amplification of Thalamic Projections to Middle Suprasylvian Cortex following Ablation of Immature Primary Visual Cortex in the Cat

The purpose of the present study was to identify expansionsin thalamic projections to the middle suprasylvian (MS) cortexthat could be linked to the sparing of visually guided behaviorsthat follow the removal of visual cortex early in postnatallife. Injections of retrograde tracers were made into the medialbank of the middle suprasylvian sulcus in intact, adult catsand in adult cats that had incurred ablations of areas 17 and18 on the day of birth (P1), P28, or     

Regional Distribution of Neurofilament and Calcium-binding Proteins in the Cingulate Cortex of the Macaque Monkey

The cingulate cortex is composed of morphologically and functionallydistinct areas. It is considered to be a major component ofthe limbic system and has been shown to subserve a wide rangeof autonomic and somatic motor functions. The anterior and posteriorregions of the cingulate cortex can be differentiated accordingto their thalamic afferents as well as their patterns of corticocorticalconnectivity. The primate cingulate cortex is traditionallydivided into a series of cytoarchitec tonic zones that can bedistinguished along a ventral-dorsal axis of differentiationin both the anterior (areas 25, 24a, 24b, and 24c), and posterior(areas 29, 30, 23a, 23b, and 23c) regions. However, little isknown about the precise cellular organization of these subareas.In the present study, we attempt to define the neuronal morphologicaland biochemical composition of the different cingulate cortexsubareas, using antibodies to the neurofilament triplet proteinand calcium-binding proteins. Results indicate that there isa strong correlation between the structure and functions ofthe cingulate cortex and the immunostaining patterns. For instance,distribution of neurofilament-rich pyramidal neurons parallelsthat of specific corticocortical and corticosubcortical systemsand is a useful marker to delineate the cingulate motor area.Calcium-binding protein-containing neurons display a high degreeof regional and laminar specialization. In particular, parvalbumin-positiveinterneurons are codistributed with neurofilament-immunoreactivepyramidal cells along the ventrodorsal and rostrocaudal axesof the cingulate cortex. Calbindin- and calretinin-positiveimmunostaining show more monotonous laminar and regional patterns,although they exhibit a particular labeling in area 29 thatmay correspond to the termination of select thalamocorticalafferents. These chemoarchitectural patterns of regional andlaminar neuronal specialization may be envisioned as the reflectionof the richness of cortical diversity in the cingulate gyrus,and make it an ideal place to explore the interplay of the distributionsof various neuron types in cortical areas of known function.     

Prenatal Development of NADPH-diaphorase-Reactive Neurons in Human Frontal Cortex

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)histochemistry was used to study the morphology and developmentof neurons that metabolize nitric oxide (NO) in the frontalcortex of human fetuses aged from 13 weeks of gestation (13W)to term, to investigate whether the two distinct types of NOneuron described in the adult develop differently. Large, heavilystained, sparsely spiny, non-pyramidal neurons (Type I) developby 15W mainly in the subplate (SP) of the cortical Anlage. Theyachieve an adult-like pattern by 32W, distributed thoughoutthe cortex and subcortical white matter, but with the highestconcentration in the white matter. Small, lightly stained cells(Type II) develop later (32W) thoughout the cortex, but especiallyin layers II-IV. and increase in number to term. NADPH-d-positivedendrites and axons appear in the cortex and white matter by15W. They include thick, radially oriented, dendritic processesfrom Type I neurons in SP and CP Their arbors expand and maturebetween 17 and 28W. Fine horizontal axons are visible in layerI by 17W. Others develop in layers II-IV from 28W, and havereached a high degree of development by term. NADPH-d-positiveaxons in the cortex seem to have both intrinsic and extrinsicorigins. Thus the two types of NADPH-d neurons found in adultprimate, including human, cortex are reflected by differentdevelopmental forms prenatally. It is concluded that NO-metabolizingneurons in the human cortex may be involved in various aspectsof development, including morphological and functional maturation,and that the late-developing Type II neurons may represent acell line specific to primates, perhaps related to the developmentof their higher cortical activity and of potential importancein the pathophysiology of diseases of cognitive function.     

Processing of Contrast Polarity of Visual Images in Inferotemporal Cortex of the Macaque Monkey

Cells in the anterior part of the inferotemporal cortex (anteriorIT) respond to moderately complex stimulus features of objectimages. To study dependency of their responses on contrast polarityof stimulus images, we selected cells with optimal stimuli thatwere defined only by shape and not related to texture or color,and examined effects of reversing the contrast of the imageor removing it except for edges between dark and bright partsof the image ("outlining").The contrast reversal produced areduction of the response to the optimal stimulus by >50%in 60% of tested cells; the outlining, in 70%. When the twotransformations were considered together, 94% of the cells showeda reduction by >50%. Effects of the transformations on shapeselectivity were also studied by comparing responses to severaldifferent shapes each of whose contours were expressed in differentways. Statistically significant changes in relative effectivenessof the different shapes as a function of contour expressionwere observed in more than half of the cells. These resultssuggest that responses of individual cells in anterior IT carryinformation about contrast polarity as well as about shape.     

Comparison of Intrinsic Connectivity in Different Areas of Macaque Monkey Cerebral Cortex

We have used small injections of biocytin to label and comparepatterns of intreareal, laterally spreading projections of pyramidalneurons in a number of areas of macaque monkey cerebral cortex.In visual areas (V1, V2, and V4), somatosensory areas (3b, 1,and 2), and motor area 4, a punctate discontinuous pattern ofconnections is made from 200-µm-diameter biocytin injectionsin the superficial layers. In prefrontal cortex (areas 9 and46), stripe-like connectivity patterns are observed. In allareas of cortex examined, the width of the terminal-free gapsis closely scaled to the average diameter of terminal patches,or width of terminal stripes. In addition, both patch and gapdimensions match the average lateral spread of the dendriticfield of single pyramidal neurons in the superficial layersof the same cortical region. These architectural features ofthe connectional mosaics are constant despite a twofold differencein scale across cortical areas and different species. They thereforeappear to be fundamental features of cortical organization.A model is offered in which local circuit inhibitory "basket"interneurons, activated at the same time as excitatory pyramidalneurons, could veto pyramidal neuron connections within eithercircular or stripe-like domains; this could lead to the formationof the pattern of lateral connections observed in this study,and provides a framework for further theoretical studies ofcerebral cortex function.     

Neural Correlates of Learning in the Prefrontal Cortex of the Monkey: A Predictive Model

The principles underlying the organization and operation ofthe prefrontal cortex have been addressed by neural networkmodeling. The involvement of the prefrontal cortex in the temporalorganization of behavior can be defined by processing unitsthat switch between two stable states of activity (bistablebehavior) in response to synaptic inputs. Long-term representationof programs requiring short-term memory can result from activity-dependentmodifications of the synaptic transmission controlling the bistablebehavior. After learning, the sustained activity of a givenneuron represents the selective memorization of a past eventthe selective anticipation of a future event, and the predictabilityof reinforcement A simulated neural network illustrates theabilities of the model (1) to learn, via a natural step-by-steptraining protocol, the paradigmatic task (delayed response)used for testing prefrontal neurons in primates, (2) to displaythe same categories of neuronal activities, and (3) to predicthow they change during learning. In agreement with experimentaldata, two main types of activity contribute to the adaptiveproperties of the network. The first is transient activity time-lockedto events of the task and its profile remains constant duringsuccessive training stages. The second is sustained activitythat undergoes nonmonotonic changes with changes in reward contingencythat occur during the transition between stages.     

Pattern in the Cortical Distribution of Prefrontally Directed Neurons with Divergent Axons in the Rhesus Monkey

Neurons with divergent branched axons have been noted in severalstructures, but their organization across cortical systems,cortical types, or cortical layers is not known. The above questionswere addressed with the aid of multiple fluorescent retrogradetracers injected in one hemisphere of the prefrontal cortexof rhesus monkeys. The prefrontal cortex is well suited forthis study because it receives input from diverse cortical systems.A small number of neurons (     

Development of Horizontal Projections in Layer 2/3 of Ferret Visual Cortex

Pyramidal cells in layer 2/3 of cat striate cortex extend longaxons that form clustered projections linking iso-orientationcolumns. Using extracellular biocytin injections in brain slices,the formation of these projections was examined in the ferretto determine whether horizontal projections exhibit similarpatterns of development in the ferret and the cat, and to relatethe time course of horizontal projection formation to the onsetof patterned visual experience and orientation selectivity.Soon after the first appearance of axon collaterals in layer2/3. around postnatal day 22 (P22), pyramidal cell axons wereuniformly distributed and unbranched for up to 1 mm from thecell body. By P26, axons began to form secondary branches 1–2mm from the cell body, with little evidence for distinct clusters.The first indication of selective elaboration of secondary branchesand retraction of unbranched collaterals occurred around P28.By P34. patchy regions of axon branches emerged, though unbranchedcollaterals were still present, followed by distinct, adult-likeclusters by P45. Although the general pattern of horizontalprojection formation closely resembles that seen in the cat(Callaway and Katz, 1990), the ferret circuitry matures earlierthan that of the cat relative to the time of eye opening. Sinceeye opening in ferrets occurs between P30 and P32, this systemof orientation-specific patches begins to develop in the absenceof patterned visual input and when most cortical cells are notyet orientation selective, suggesting a prominent role for spontaneousactivity in initiating cluster formation. The refinement ofclustered connections, however, does occur synchronously withthe maturation of orientation-selective responses (Chapman andStryker, 1993).     

The Effects of Aging on Area 46 of the Frontal Cortex of the Rhesus Monkey

An examination of cortex of area 46 in the floor of the principalsulcus in the frontal lobe of the rhesus monkey has been carriedout using three young (4–6 years of age), one middle-aged(12 years of age), and five old (25–32 years of age) rhesusmonkeys. Light microscopic examination revealed no age-relatedchange in the thickness of the cortex, and no changes in thefrequency of profiles of neurons displaying nuclei and containedin 250-µm-wide strips of 1-µm-thick sections. Sincethe diameters of the nuclei of the neurons were found to bethe same in the young and old monkeys, it was concluded thatthere was no change in the numbers of neurons beneath similarareas of cortical surface of area 46 with age. This conclusionwas reinforced by an electron microscopic examination, sincethere was no suggestion of degeneration of the cell bodies ofthe neurons, which accumulated but little lipofuscin in theold monkeys. However, there were signs of degeneration in someof the dendrites in the upper layers of the cortex in the oldmonkeys, especially in layer 1, in which many of the dendriteshad lost organelles from their cytoplasm. The other notablechange was a degeneration of myelinated axons in the deep layersand white matter in some of the old monkeys. In contrast tothe neurons, the effects of aging on the neuroglial cells andpericytes were very obvious, since in the old monkeys each typeof neuroglial cell accumulated large inclusions within its cytoplasm.Prior to fixation, these monkeys had been behaviorally testedusing a series of spatial and visual recognition tasks, whichrevealed that relative to the young monkeys, the old monkeysas a group displayed memory impairment. On one task, the extentof the impairment for each old monkey correlated well with theextent of degeneration of myelinated fibers in the cortex andwhite matter. Consequently, it is suggested that age-relatedcognitive changes are unlikely to be a result of a loss of neurons,but might be due to an alteration in connections between thecortex and other brain structures.