《认知神经科学》课程教学资源（参考文献）[Goldman-Rakic, P. S.（1987）]Development of cortical circuitry and cognitive function

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PRI PREFRONTAL FIG. 2.—A, Diagram of the three major subdivisions of the frontal lobe in nonhuman primates. The major sulci are the principal sulcus (PS) in prefrontal cortex, tiie arcuate sulcus (AS) that separates the prefrontal and premotor areas, and the central sulcus (CS) that is the boundary between the frontal and parietal lobes. Furdier subdivisions within prefrontal cortex are indicated: (a) inferior convexity— Brodmann's area 12; (b) cortex surrounding the principal sulcus—Brodmann's area 46; and (c) the frontal eye field—Brodmann's area 8. The mi^jor focus of the present article is Brodmann's area 46. B, Summary of areas in the posterior parietal cortex dmt process visuospatial and somatic-related infonnation (7m, lip, la, and 7b) and the distribution of their projections in die principal sulcus as revealed by correspondence in a zip-a-tone pattem (from Cavada & Coldman-Rakic, 1985), C, Summary of direct and indirect circuits linking the principal sulcus with structures involved in memory—the hippocampal formation. D, Summary ofmajor projections from the principal sulcus to areas of the brain diat are involved in motor control. Other abbreviations: IS, intraparietal sulcus; CA, Ammon's hom of the hippocampus; CC, corpus callosum; CD, caudate nucleus; CING and RS, cingulate and retrosplenial cortices; CML, caudomedial lobule; CS, collateral sulcus; DG, dentate gyms; PSUB, presubiculim; TH, TF, and 28, parahippocampal areas; OTS, occipitotemporal sulcus; SC, superior colliculus; and SMA, supplementary motor cortex

Patricia S.Goldman-Rakic 607 nation The primacy of the al nyed of evidence: on necessary ster the location of input to the ical stud (Am 00贤 arietal rozoski Pe ides Par 1984 studies 3 hich is the corticai 1980 Lynch. onal respons one the principal sulcus should act rent l ines of e tructure that 1984a 1987 (Co ctions the duce a dou ections un d le from 1970 ed hand the motor control 63 stin h5o0s cross es h tion o inhi out some Fig. ven both 1977a K5 important,prir ndet, t ed re and 84 Go ,1972b,1972c uitry exists components s of c onnections).sto circuits) and (pre examp increase connecti (or right) Columnar and laminar org 0 bee The archite die an of principe sulcus make 0阳 modular type o until the response is made. e cortex cus as dis major comnec eredetail.to the point th ete in width sulc sized col s of n be nections and principa pro The as has beer example, the in organize into six layers,and

tationa] information. The primacy of the prin￾cipal sulcus for delayed-response function has been established by at least five separate lines of evidence; (1) ablation studies (Blum, 1952; Butters, Pandya, Stein, & Rosen, 1972; Goldman & Rosvold, 1970; Mishkin & Man￾ning, 1978); (2) pharmacolo^cal studies (Am￾sten & Goldman-Rakic, 1985; Brozoski, Brown, Rosvold, & Goldman, 1979); (3) mi￾crostimulation studies (Stamm, 1969); (4) electrc^hysiological recording (Fuster, 1973, 1980; Kubota & Niki, 1971; Niki, 1974a, 1974b, 1974c; Kojima & Goldman-Rakic, 1982, 1984); and (5) functional inactivation, for example, hypodiermic iractivation (Alex￾ander & Goldman, 1978; Fuster & Alexander, 1971). These different lines of research have been extensively reviewed (Fuster, 1980; Goldman-Rakic, 1984a, 1987; Goldman￾Rakic, Isseroff, Schwartz, & Bugbee, 1983). Briefly, remold of the princi{»l sulcus is sufficient to produce a profound delayed￾response deficit, whereas equal-sized lesions in other portions of the front^ lolw have little effect (Goldman & Rosvold, 1970). Delayed￾response performance is disrupted in die first few seconds of the delay when electrical stimulation is applied across the principal sul￾cus (Stamm, 1969). Electrc^hysiological re￾cording in animals performing delayed￾response tasks has established that principal sulcal neurons can be driven both by auditory and visual stimuli (e.g., Azuma & Suzuki, 1984; Kojima, 1980; Niki, 1972a; Suzuki & Azuma, 1985). Most important, principal sul￾cal neurons respond in time-locked foshion to the xnaior events of a delayed response (Fus￾ter, 1973; Kojima & Goldman-Rakic, 1982, 1984) or delayed alternation (Kubota & Niki, 1971; Niki, 1972b, 1972c) trial. Of particular relevance is a class of cell that increases its firing selectively during the delay period of the task and in relation to die position of the stimulus. For example, a neuron may increase its dischfuge during the delay only if die cue had been on the left (or ri^t) (for review, see Fuster, 1980, 1985; also Golcbnan-Rakic, 1984a, 1987). This and other response charac￾teristics of principal sulcus neurons make them excellent candids^s for holding visuo￾spatial information "on line" until die correct response is made. Connectivity of the principal sulcus.— Over the past decade, die rasgor connections of the principal sulcus have been worfted out in considerable detail, to the point that rela￾tions between specific connections and specific functions can be seen and ap￾preciated (for reviews see Goldman-R^c, 1984b, 1984c, 1987). For example, die in￾Patricia S. Goldman-Rakic 607 volvement of the principal sulcus in delayed response implies access to visuospatial infor￾mation necessary to register the location of the food reward. Indeed, the major cortical input to the posterior two-thirds of die princi￾pal sulcus originates in the posterior parietal cortex (Fig. 2B; Goldman-Rakic & Schwartz, 1^2; Petrides & Pandya, 1984; Schwartz & Goldman-Rakic, 1984), which is the cortical center for spatial information processing (Mountcastle, Motter, Steinmetz, & Dufiy, 1984; Lynch, Mountcastle, Tdbot, & Yin, 1977). Given the mnemonic aspect of de￾layed-response functions, one mi^ t presume that the principal sulcus shotild interact with die hippocampus—the m^or subcortical structure that is crucial for certain forms of memory (Gohen, 1984; Squires & Butters, 1984). In support, multiple direct and indirect connections connect the principal sulcus with the hippocampus, and these connections un￾doubtedly play a m£^or role in assessing memories from long-term storage for use in the task at hand (Fig. 2C; Goldman-iUkic, Selemon, & Schwartz, 1984). The anatomy of motor control by which principal sulcus neurons participate in the selection or inhibi￾tion of responses has also been examined and worked out in some detail (Fig. 2D). This anatomy includes projections from the jainci￾pal sulcus to the caudate nucleus (Goidman & Nauta, 1977a; Selemon & Goldman-Rakic, 1985; Yeterian & Van Hoesen, 1978), connec￾tions with the motor thalamus (Goldman￾Rakic & Porrino, 1985; Ilinsky, Jouandet, & Goldman-Rakic, 1985), and with the deep "motor" layers of the superior colliculus (Fries, 1984; Goldman & Nauta, 1976). Thus, all circuitry exists for the components of de￾layed-response performance—visuospatial in￾put (pariet^-prefrontal connections), storage/ recall mechanisms (prefrontal-hippocMnpal circuits), and motor commands (preftontal connections with motor structures). Columnar and laminar organisation of the prifuHpal sulcus.—The microarchitecture of the principal sulcus has also been studied to some degree, and several studies have re￾vealed that diis cortex has a modular type of organization. For example, fibers originating in the parietal cortex (so-celled associational fibers) terminate in the principal sulcus as dis￾tinct vertically oriented columns about one￾half millimeter in width (Goldman & Nauta, 1977b). These columns altemate with equal￾sized colunms of fibers from the contralateral principal sulcus (so-called callosal pro￾jections) (Fig. 3, Goldman-Rakic & Schwartz, 1982). The cortex, as has been mentioned, is organized into six layers, and both callosal

608 Child Development and associational fibers tend to terminate review,see Rakic Goldman-Rakic,1984) Ou focus has been on of axon eigf detal) y r yer areas that comprise the sys nce of the phic methods for studvine The sign ayering odoropetonted re t ml ets of inco of afferents have y in the dis ctive proje it w iographic ca vas the ava n in fig mad layer III pro fetal monkeys ore this metho eoiwgfst ng br ons for ause the e ca te silver) ade m 100 sbcortical structures;neu sin layer VE pp to de ping anim ect selectively to the tha (Fig. vival time aptcachihe ure and ngortiea d ser nt and system (Leo a 1973 lity of the Finally. the re because one could ation of con for ex aseat adult function ca It is wChodtdsooveredwihsihwerimpregna6e out that By cont radio phic tech sulcus an I that ga ioactive isot nt res ini cted size of re at the site begin the ds o th t6 irth or at any other arbi品 eins ancy,the processes and he proteins are rion of the to dg of cell bncamRoebe,ecd ceden logy,the precise survival times optimal for t in my labdy O of ten ina field liest embryor es that i dist on of target 6caeial r ev mpts tha s by whi the axo ns reach their targ e pla 6 at or a birth in smal rlier in the the brain rk:the Sodman-Rakic 1982).It here to develop nniques for 小12 pre nt any giv

608 Child Development and associational fibers tend to terminate selectively in layers IV and I, while associa￾tional fibers additionally terminate in layer VI (see Fig. 3 for details). The cortex also has a radial or horizontal geometry due to its distinct six-layered or￾ganization. The significance of the layering pattem is that cells in the specific layers that are targets of incoming callosal or associa￾tional afferents have distinctive projection targets in subcortical and/or other cortical structures. For example, as shown in Figure 3, pyramidal neurons in layer III project primarily to other cortical areas, bodi widiin the same (associational neurons) and opposite (callosal neurons) hemispheres. While over 80% of callosal and associational neurons originate in layer III, layer V is the msyor source of projections to the caudate nucleus and putamen, to the colliculus, and to other subcordcal structures; neurons in layer VI project selectively to the thalamus (Fig. 3). Knowing these facts, one can begin to ap￾preciate the synaptic architecture and wiring diagrams underlying a specific cortical func￾tion. Prenatal Development of Prefrontal Connections Background for prenatal studies.—It is reasonable to assume that adult function can emerge only if the proper connections and circuitry necessary to carry out that fimction are established. The principal sulcus and its interconnections provide a natural model sys￾tem for the study of the biological basis of die particular type of cognitive capacity indexed by delayed-response tasks, namely, the guid￾ance of behavior by stored representations. Although in theory it is possible to begin the developmental study of structure-function re￾lations at birth or at any other arbitrary point in infancy, the processes and mechanisms of development are complex, onierly, and syn￾chronized and can best be appreciated only by comprehensive analysis of antecedent causes. Accordingly, the study of prefrontal cortex development in my laboratory includes analysis of the earliest embryonic ages that it is feasible to study in primates. It is important to realize that the critical cellular events that take place at or after birth in small mammals, for example, the rat, occur much earlier in the primate, well before birth (for fuller discus￾sion of these events, see Goldman-Rakic, 1986; Rakic & Goldman-Rakic, 1982). It was therefore necessary to develop techniques for prenatal surgery and prenatal intervention that could be applied to the primate brain (for review, see Rakic & Goldman-Rakic, 1984). Our focus has been on the outgrowdi of axons and the establishment of synaptic connections between the key areas that comprise the sys￾tem underlying delayed response. Autoradiographic methods for studying prefrontal connections.—Very few studies have ever been conducted on the develop￾ment of connectivity in the primate brain, and it was the availability of the autoradiographic method in conjunction with prenatal surgery that made it feasible to trace connections in fetal monkeys. Before this method, connec￾tions were traced by performing rather large lesions of structures, and after an appropriate survival period, examining brain sections for degenerating axons and terminals (that could be visualized because they selectively im￾pregnate silver). This mediod had several drawbacks that made it particularly difficult to apply to developing animals. The optimal sur￾vival time for visualizing the products of de￾generation had to be worked out empirically and separately for every age point and neural system (Leonard, 1973). The reliability of the silver impregnation varied with investigators. Finally, the resolution of connections was in￾trinsically poor because one could describe projections only between large areas. Golum￾nar distribution of connections, for example, was not discovered with silver-impregnation methods. By contrast, the autoradiographic tech￾nique was a highly reliable method that gave clear and consistent results. Small quantities of radioactive isotopes are injected into desig￾nated areas; the size of the area injected can be controlled by the volume of isotope in￾jected. Neurons at the site of injection absorb die mdiolabeled amino acids into their cell bodies. In the cell body, the amino acids are converted into proteins by normal protein synthesis, and these proteins are transported from the cell dirough its axon to the terminal region of die cell. From knowledge of cell biology, the precise survival times optimal for transport to occur can be accurately predicted to optimize visualization of terminal fields (the distribution of labeled axons in target stmctures) and for determination of die path￾ways by which the axons reach their targets. Sections cut throu^ the brain are mounted on slides that are dipped in photographic emulsion in the dark; the emulsion is exposed only by the beta emissions radiating from labeled cells, axons, and terminals that may be present within any given section. After 8— 12 weeks, the slides are developed and the exposed areas appear as darkened grains