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Effects of restricted cochlear lesions in adult cats on the frequency organization of the inferior colliculus.

Restricted cochlear lesions in adult animals result in plastic changes in the representation of the lesioned cochlea, and thus in the frequency map, in the contralateral auditory cortex and thalamus. To examine the contribution of subthalamic changes to this reorganization, the effects of unilateral mechanical cochlear lesions on the frequency organization of the central nucleus of the inferior colliculus (ICC) were examined in adult cats. Lesions typically resulted in a broad high-frequency hearing loss extending from a frequency in the range 15-22 kHz. After recovery periods of 2.5-18 months, the frequency organization of ICC contralateral to the lesioned cochlea was determined separately for the onset and late components of multiunit responses to tone-burst stimuli. For the late response component in all but one penetration through the ICC, and for the onset response component in more than half of the penetrations, changes in frequency organization in the lesion projection zone were explicable as the residue of prelesion responses. In half of the penetrations exhibiting nonresidue type changes in onset-response frequency organization, the changes appeared to reflect the unmasking of normally inhibited inputs. In the other half it was unclear whether the changes reflected unmasking or a dynamic process of reorganization. Thus, most of the observed changes were explicable as passive consequences of the lesion, and there was limited evidence for plasticity in the ICC. The implications of the data with respect to the primary locus of the changes and to the manner in which they contribute to thalamocortical reorganization are considered.

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Expression of androgen receptor mRNA in the brain of Gekko gecko: implications for understanding the role of androgens in controlling auditory and vocal processes.

The neuroanatomical distribution of androgen receptor (AR) mRNA-containing cells in the brain of a vocal lizard, Gekko gecko, was mapped using in situ hybridization. Particular attention was given to auditory and vocal nuclei. Within the auditory system, the cochlear nuclei, the central nucleus of the torus semicircularis, the nucleus medialis, and the medial region of the dorsal ventricular ridge contained moderate numbers of labeled neurons. Neurons labeled with the AR probe were located in many nuclei related to vocalization. Within the hindbrain, the mesencephalic nucleus of the trigeminal nerve, the vagal part of the nucleus ambiguus, and the dosal motor nucleus of the vagus nerve contained many neurons that exhibited strong expression of AR mRNA. Neurons located in the peripheral nucleus of the torus in the mesencephalon exhibited moderate levels of hybridization. Intense AR mRNA expression was also observed in neurons within two other areas that may be involved in vocalization, the medial preoptic area and the hypoglossal nucleus. The strongest mRNA signals identified in this study were found in cells of the pallium, hypothalamus, and inferior nucleus of the raphe. The expression patterns of AR mRNA in the auditory and vocal control nuclei of G. gecko suggest that neurons involved in acoustic communication in this species, and perhaps related species, are susceptible to regulation by androgens during the breeding season. The significance of these results for understanding the evolution of reptilian vocal communication is discussed.

Androgens↗

Time course of embryonic midbrain and thalamic auditory connection development in mice as revealed by carbocyanine dye tracing.

Central auditory connections develop in mice before the onset of hearing, around postnatal day 7. Two previous studies have investigated the development of auditory nuclei projections and lateral lemniscal nuclear projections in embryonic rats, respectively. Here, we provide detail for the first time of the initiation and progression of projections from the inferior colliculus (IC) to the medial geniculate body (MGB) and from the MGB to the auditory cortex (AC). Overall, the developmental progression of projections follows that of terminal mitoses in various nuclei, suggesting the consistent use of a developmental timetable at a given nucleus, independent of that of other nuclei. Our data further suggest that neurons project specifically and reciprocally from the MGB to the AC as early as embryonic day 14.5. These projections develop approximately a day before the reciprocal connections between the MGB and IC and before development of projections from the auditory nuclei to the IC. The development of IC projections is prolonged and progresses from rostral to caudal areas. Brainstem nuclear projections to the IC arrive first from the lateral lemniscus nuclei then the superior olive and finally the cochlear nuclei. Overall, the auditory connection development strongly suggests that most of the overall specificity of nuclear connections is set up at least 2 weeks before the onset of sound-mediated cochlea responses in mice and, thus, is likely governed predominantly by molecular genetic clues.

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Acoustic stria: anatomy of physiologically characterized cells and their axonal projection patterns.

The mammalian cochlear nucleus (CN) has been a model structure to study the relationship between physiological and morphological cell classes. Several issues remain, in particular with regard to the projection patterns and physiology of neurons that exit the CN dorsally via the dorsal (DAS), intermediate (IAS), and commissural stria. We studied these neurons physiologically and anatomically using the intra-axonal labeling method. Multipolar cells with onset chopper (O(C)) responses innervated the ipsilateral ventral and dorsal CN before exiting the CN via the commissural stria. Upon reaching the midline they turned caudally to innervate the opposite CN. No collaterals were seen innervating any olivary complex nuclei. Octopus cells typically showed onset responses with little or no sustained activity. The main axon used the IAS and followed one of two routes occasionally giving off olivary complex collaterals on their way to the contralateral ventral nucleus of the lateral lemniscus (VNLL). Here they can have elaborate terminal arbors that surround VNLL cells. Fusiform and giant cells have overlapping but not identical physiology. Fusiform but not giant cells typically show pauser or buildup responses. Axons of both cells exit via the DAS and take the same course to reach the contralateral IC without giving off any collaterals en route.

Acoustic Stimulation↗

Quantitative changes in calretinin immunostaining in the cochlear nuclei after unilateral cochlear removal in young ferrets.

Neurons of the cochlear nuclei receive axosomatic endings from primary afferent fibers from the cochlea and have projections that diverge to form parallel ascending auditory pathways. These cells are characterized by neurochemical phenotypes such as levels of calretinin. To test whether or not early deafferentation results in changes in calretinin immunostaining in the cochlear nucleus, unilateral cochlear ablations were performed in ferrets soon after hearing onset (postnatal day [P]30-P40). Two months later, changes in calretinin immunostaining as well as cell size, volume, and synaptophysin immunostaining were assessed in the anteroventral (AVCN), posteroventral (PVCN), and dorsal cochlear nucleus (DCN). A decrease in calretinin immunostaining was evident ipsilaterally within the AVCN and PVCN but not in the DCN. Further analysis revealed a decrease both in the calretinin-immunostained neuropil and in the calretinin-immunostained area within AVCN and PVCN neurons. These declines were accompanied by significant ipsilateral decreases in volume as well as neuron area in the AVCN and PVCN compared with the contralateral cochlear nucleus and unoperated animals, but not compared with the DCN. In addition, there was a significant contralateral increase in calretinin-immunostained area within AVCN and PVCN neurons compared with control animals. Finally, a decrease in area of synaptophysin immunostaining in both the ipsilateral AVCN and PVCN without changes in the number of boutons was found. The present data demonstrate that unilateral cochlear ablation leads to 1) decreased immunostaining of the neuropil in the AVCN and PVCN ipsilaterally, 2) decreased calretinin immunostaining within AVCN and PVCN neurons ipsilaterally, 3) synaptogenesis in the AVCN and PVCN ipsilaterally, and 4) increased calretinin immunostaining within AVCN and PVCN neurons contralaterally.

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Projections from the spinal trigeminal nucleus to the cochlear nucleus in the rat.

The integration of information across sensory modalities enables sound to be processed in the context of position, movement, and object identity. Inputs to the granule cell domain (GCD) of the cochlear nucleus have been shown to arise from somatosensory brain stem structures, but the nature of the projection from the spinal trigeminal nucleus is unknown. In the present study, we labeled spinal trigeminal neurons projecting to the cochlear nucleus using the retrograde tracer, Fast Blue, and mapped their distribution. In a second set of experiments, we injected the anterograde tracer biotinylated dextran amine into the spinal trigeminal nucleus and studied the resulting anterograde projections with light and electron microscopy. Spinal trigeminal neurons were distributed primarily in pars caudalis and interpolaris and provided inputs to the cochlear nucleus. Their axons gave rise to small (1-3 microm in diameter) en passant swellings and terminal boutons in the GCD and deep layers of the dorsal cochlear nucleus. Less frequently, larger (3-15 microm in diameter) lobulated endings known as mossy fibers were distributed within the GCD. Ventrally placed injections had an additional projection into the anteroventral cochlear nucleus, whereas dorsally placed injections had an additional projection into the posteroventral cochlear nucleus. All endings were filled with round synaptic vesicles and formed asymmetric specializations with postsynaptic targets, implying that they are excitatory in nature. The postsynaptic targets of these terminals included dendrites of granule cells. These projections provide a structural substrate for somatosensory information to influence auditory processing at the earliest level of the central auditory pathways.

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Descending projections from the auditory cortex to the inferior colliculus in the gerbil, Meriones unguiculatus.

Corticofugal projections to the auditory midbrain, the inferior colliculus (IC), influence the way in which specific sets of IC neurons process acoustic signals. We used retrograde tracer (Fluorogold, Fluororuby, microbeads) injections in the IC to study the morphology and location of cortico-collicular projecting neurons and anterograde tracer (dextran biotin) injections in auditory cortical fields to describe the distribution of terminals in the IC. Nissl staining, cytochrome oxidase activity, and neurofilament SMI32 immunostaining were used to delimit the different auditory areas. We defined a primary or "core" auditory cortex and a secondary "caudal" auditory area containing layer V pyramidal neurons that project to the IC. These projections target the central nucleus of the IC (CNIC) ipsilaterally and the IC cortices bilaterally, with the ipsilateral component predominant. Other secondary auditory areas, dorsal and ventral to the core, do not directly participate in this projection. The ventral secondary cortex targets midbrain periaqueductal gray. The projection from the core cortex originates from two classes of layer V pyramidal cells. Cells presenting a tufted apical dendrite in layer I have dense terminal fields in the IC cortices. Pyramids lacking layer I dendritic tufts target the CNIC in a less dense but tonotopic manner. The caudal cortex projection originates from smaller layer V pyramids and targets the IC cortices with dense terminal fields. Descending auditory inputs from the core and caudal areas converge in the dorsal and external cortices of the IC. Descending connections to the gerbil IC form a segregated system in which multiple descending channels originating from different neuronal subpopulations may modulate specific aspects of ascending auditory information.

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Functional organization and hemispheric comparison of primary auditory cortex in the common marmoset (Callithrix jacchus).

Hemispheric fine-grain maps of primary auditory cortex (AI) were derived from microelectrode penetrations in the temporal gyrus of the common marmoset (Callithrix jacchus) to 1) compare the functional organization of AI in the marmoset with other mammalian species and 2) compare the right and left AI maps in individual monkeys. Frequency receptive fields (FRFs) were recorded with pure tones. Five FRF parameters were analyzed: characteristic frequency, threshold, sharpness of tuning 10 dB and 40 dB above threshold, and minimum response latency. The present study confirms that the functional organization of AI is characterized by a robust tonotopic frequency gradient overlaid with spatially clustered distributions of other FRF parameters. Globally, this functional organization of AI in the common marmoset is similar to that in other mammalian species. With respect to within-subject hemispheric comparisons of the five FRF parameters, a coherent pattern of asymmetry is not evident in marmoset AI. The overall results indicate that the basic functional organization between hemispheres is similar but not identical.

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Tone responses in core versus belt auditory cortex in the developing chinchilla.

Single-unit responses to tone pip stimuli were isolated from numerous microelectrode penetrations of core primary auditory cortex (AI) and a dorsocaudal (DC) belt region in the ketamine-anesthetized chinchilla (laniger). Results are reported at postnatal day 3 (P3), P15, P30, and from adult animals. The AI core could be distinguished from the DC belt on the basis of its strict tonotopic organization, evident in all chinchillas studied (including the youngest). Averaged by age group and compared to their core counterparts, belt neurons generally had similar absolute (spike rate) thresholds and onset latencies (at a given sound pressure level), but lower maximum spike rates, broader tuning bandwidths, and more complex (multipeaked) receptive fields. Most notably, the fraction of complex belt units in the near-newborn (P3) group was high (approximately 50%), and did not systematically increase with age, while that of complex core units was approximately 10% at P3 and increased steadily to about 40% in adulthood. These results provide further evidence to support the hypothesis that, at least to some extent, core and belt auditory cortex may constitute parallel processing streams which represent different aspects of complex acoustic stimuli.

Aging↗

Organization of the inferior colliculus of the gerbil (Meriones unguiculatus): differences in distribution of projections from the cochlear nuclei and the superior olivary complex.

The inferior colliculus (IC) receives its major ascending input from the cochlear nuclei, the superior olivary complex, and the nuclei of the lateral lemniscus. To understand better the terminal distribution of the inputs from these sources relative to one another, we made focal injections of a retrograde tracer, biotinylated dextran amine, in different parts of the IC in 74 gerbils (Meriones unguiculatus). The cases could be divided into three groups based on counts of labeled cells in brainstem auditory nuclei. Group 1 cases had labeled cells in both the cochlear nuclei and the lateral and medial superior olivary nuclei. Group 2 cases had labeled cells in the cochlear nuclei but few or none in the lateral and medial superior olivary nuclei. Both groups had labeled cells in the nuclei of the lateral lemniscus and the superior paraolivary nucleus. Group 3 cases had few labeled cells in any of the ascending auditory pathways. The group to which a case belonged was strongly related to the location of the injection site in the IC. The injection sites for both group 1 and group 2 were located in the central nucleus, but those for group 1 tended to be located laterally relative to those for group 2, which were located more medially and caudally. The injection sites for group 3 cases lay outside the central nucleus of the IC. The two regions of the central nucleus of the IC, distinguished on the basis of connectivity, are likely to subserve different functions.

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Intracellular responses and morphology of rat ventral complex of the lateral lemniscus neurons in vivo.

The function of the ventral and intermediate nuclei of the lateral lemniscus (VNLL and INLL), collectively termed ventral complex of the lateral lemniscus (VCLL), is unclear. Several studies have suggested that it plays a role in coding the temporal aspects of sound. In our study, a sample (n = 161) of intracellular responses to dichotically presented noise or tone bursts was collected from the VCLL of urethane-anesthetized rats in vivo. Intracellular recordings revealed six distinct response types to tones, distinguished by their synaptic and membrane characteristics as well as firing pattern. Three of these response types were correlated with distinct cellular morphologies revealed by intracellular injection of neurobiotin. 3D reconstructions of recorded neurons within the VCLL showed the spatial distribution of various response properties, including response type, laterality, characteristic frequency (CF), and binaural influences. Cells that responded to monaural (55%) or binaural (45%) stimulation were distributed throughout the VCLL. Almost all VCLL units were responsive to contralateral stimulation (97%). Most neurons were excited by contralateral stimulation (83%), many exclusively (43%), and some in conjunction with ipsilateral inhibition (28%) or excitation (12%). The INLL contained mostly binaural neurons (65%), typically with ipsilateral inhibition and contralateral excitation. These results indicate that the VCLL is not a monaural structure and there is a dorsal-ventral segregation of binaural and monaural cells. 3D reconstructions of intracellular CFs did not reveal the presence of any tonotopic arrangement within the VCLL. Presumably, the proposed timing role of this structure does not require a systematic representation of tonal frequency.

Acoustic Stimulation↗

Organization and development of brain stem auditory nuclei of the chicken: tonotopic organization of n. magnocellularis and n. laminaris.

Extracellular recordings of responses to tone-burst stimulation were used to determine the tonotopic organization of n. magnocellularis (NM) and n. laminaris (NL) in hatching chickens. NM cells show "primary-like" response patterns to ipsilateral stimulation, and are arranged in dorso-ventral isofrequency columns. Units responding to the highest frequency tones (about 4,100 Hz) are situated at the rostromedial pole of the medial division. Units with lower characteristic frequencies (CF's) are found at successively caudal and lateral sites, until extremely low CF's ( less than 500 Hz) are represented dorsoventrally in the daudolateral tail of the lateral division. No evidence was found of auditory input to the region which receives projections from the macula lagena. NL receives polarized, binaural, excitatory input. Units have similar CF's and thresholds to tones presented to either ear. The tonotopic organization in NL matches that found in NM--high CF's rostromedially and low CF's caudal and lateral. Quantitative procedures were developed for relating CF to the position of a unit within either nucleus. These analyses account for 79% and 89% of the frequency variance found within NM and NL, respectively, and predict the CF of a neuron by its position within each nucleus.

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Distinct auditory and lateral line nuclei in the midbrain catfishes.

The catfish torus semicircularis (TS) comprises two major nuclei, which are specialized to process separately inputs of three acousticolateral modalities: VIII nerve acoustic input in one, and lateral line mechanoreceptive and electroreceptive input in the other. Electrophysiological recording and mapping experiments demonstrate a medial auditory region, a lateral electroreceptive region, and an intercalated mechanoreceptive region in the TS Nissl and Golgi-Cox preparations distinguished two rostrocaudally elongate, nuclear divisions, which correlate, one with the auditory and the other with the mechano- and electroreceptive regions. The medially positioned auditory nucleus is here called the nucleus centralis. The nucleus centralis appears as a rostrally flattened cylinder of uniformly packed cells, covered dorsally and laterally by a fiber rind. Cells within this nucleus conform to one of three general cell types based upon somatic and dendritic morphology: type 1 cells, which are the most abundant" have a single major primary dendrite and an axon typically arising from the same somatic pole; type 2 cells have two major primary dendrites and an axon, which issues from a third distinct somatic pole; and type 3 cells have several major primary dendrites and their axons are associated with one of the major somatic poles. No systematic orientation of dendrites could be found in the nucleus centralis. The laterally positioned lateral line nucleus, to be called the nucleus lateralis, includes two subdivisions: a large pars lateralis containing predominantly electroreceptive units, and a smaller, ventromedial pars medialis encompassing predominantly mechanoreceptive units. Each subdivision is found to be somatotopically organized, inputs from the head projecting to rostral areas and inputs from the tail to caudal areas. Although the cell types resemble those described for the nucleus centralis, a greater degree of cytoarchitectural orderliness is discernible: (a) cells in the nucleus lateralis group into four, alternating cell-poor cell-rich, layers; and (b) the dendritic fields of many type 1 and type 2 cells located in layer II tend to orient in a rostrodorsal-caudoventral attitude, perpendicular to the laminar planes. Fink-Heimer preparations of brains with unilateral, lateral line lobe lesions demonstrate heavy fiber and terminal degeneration confined to the nucleus lateralis on both sides. Lateral line fibers ascend bilaterally in the lateral halves of the lateral lemnisci. At the level of the dorsal oculomotor nucleus the lemniscal fibers in this portion split into two fascicles, one proceeding rostrally to innervate the rostral portion of the nucleus lateralis, and the other arching back dorsolaterally to innervate the caudal portions of the nucleus.

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Sites on termination on the saccular macula of auditory nerve fibers in the goldfish as determined by intracellular injection of procion yellow.

Procion yellow dye was injected intracellularly into large auditory fibers of goldfish to investigate the relationship between the response type of these fibers and their site of termination in the saccular macula. Fibers which responded to the rarefaction phases of sound were found to terminate on the hair cells located in the ventral half of the saccular macula, while those which responded to the compression phases were found to terminate on the dorsally located hair cells. A third group of fibers, which responded to both sound phases, was found to bifurcate outside the saccular macula and terminate on both dorsally and ventrally located hair cells. Some of the fibers of this group were found to trifurcate before entering the saccular macula. Results obtained in the present study, in conjunction with the findings on the orientation of hair cells within the sensory macula, can explain the mechanism underlying the presence of three different response types of fibers in the auditory nerve of the goldfish.

Acoustic Stimulation↗

Sources and terminations of callosal axons related to binaural and frequency maps in primary auditory cortex of the cat.

The distributions of sources and terminals of callosal fibers in the high-frequency representation of AI were related to binaural and frequency maps in combined anatomical and electrophysiological experiments. Sources of callosal axons were retrogradely labeled with HRP. Distributions of axon terminals were determined by autoradiographic labeling with [3H]-proline and anterograde degeneration following callosal section. Regions in which cells exhibit summation or ipsilateral dominance and suppression contain higher concentrations of sources and terminals of callosal fibers than do regions in which cells exhibit monaural contralateral responses or contralateral dominance and suppression. Callosal axon terminals aggregate into columns. In sections cut parallel to the cortical surface callosal columns take on complex forms that exhibit certain consistent features. Two prominent elongated columns separated by a narrow zone of sparse callosal innervation run in a rostrodorsal to caudoventral direction through AI crossing several octaves of the frequency representation. Ventral to these columns, along the AI-AII border, less densely labeled callosal columns are in evidence. Low frequency representations of AI are interconnected but details of their innervation patterns were not worked out. Outside of AI there are regions that contain complex configurations of callosal columns. Several morphologically distinct types of neurons, located in laminae III through VI, were retrogradely labeled following injections of HRP into the opposite AI. About 94% of callosal neurons are pyramidal cells of layers III and IV.

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Some features of the spatial organization of the central nucleus of the inferior colliculus of the cat.

A series of neuroanatomical and neurophysiological experiments have been conducted within the central nucleus of the inferior colliculus (ICC) of the cat in order to determine some features of the spatial organization of the nucleus. Results from these experiments have demonstrated: (1) the origins of the auditory brain stem afferents to ICC and the topography of those projections in relation to the cochleotopic organization of ICC; (2) the segregation of at least some of those brain stem projections within ICC; and (3) ICC neurons with similar response properties (response properties which are often similar or identical to those of neurons in brain stem auditory nuclei) are often clustered within the nucleus. These results provide evidence that the laminated division of the ICC probably consists of anatomically, physiologically, and functionally distinct subdivisions and that some aspects of auditory sensation may be encoded or represented separately (i.e., in spatially distinct "regions") within the nucleus.

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Tonotopic organization in auditory cortex of the cat.

Microelectrode mapping techniques were employed in the cat's auditory cortex to relate the best frequencies of a large population of neurons with their spatial loci. Based upon the best-frequency distribution, the auditory region was divided into four complete and orderly tonotopic representations and a surrounding belt of cortex in which the tonotopic organization was more complex. The four auditory fields occupy a crescent-shaped band of tissue which comprises portions of both the exposed gyral surfaces and sulcal banks of the ectosylvian cortex. The anterior auditory field (A) is situated most rostrally upon the anterior ectosylvian gyrus. It extends upon the ventral bank of the suprasylvian sulcus and upon the banks of the anterior ectosylvian sulcus. Adjoining field A caudally is the primary auditory field (AI), which extends across the middle ectosylvian gyrus and portions of both banks of the posterior ectosylvian sulcus. The representations of the highest best frequencies in fields A and AI are contiguous. Caudal and ventral to AI are located the posterior (P) and ventroposterior (VP) auditory fields. They lie mainly upon the caudal bank of the posterior ectosylvian sulcus but also extend upon the rostral bank and upon the posterior ectosylvian gyrus. The low best-frequency representations of fields AI and P are contiguous, whereas the low best-frequency representation of field VP lies near the ventral end of the posterior ectosylvian sulcus. Fields P and VP are joined along their middle and high best-frequency representations. Within each auditory field isofrequency lines defined by the spatial loci of neurons with similar best frequencies are oriented orthogonal to the low-to-high best-frequency gradients.

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Patterns of cortico-cortical connections related to tonotopic maps in cat auditory cortex.

Topographic distributions of cortico-cortical projections from the primary (AI), anterior (A), posterior (P), ventroposterior (VP), and second (AII) auditory fields were studied in relation to tonotopic maps in combined anatomical and electrophysiological experiments. Distributions of axon terminals were determined by autoradiographic labeling with tritiated proline and leucine. Each of fields A, AI, P, and VP is connected with the other three in the same hemisphere as well as with a number of other auditory cortical areas. Additionally, neurons in each of the fields studied were found to project to the lateral bank of the collateral fissure. In general, regions near the injection site receive more densely labeled projections than do more distant targets. Neurons in each field were found to project to one or more areas in th opposite hemisphere. Only similar portions of the best-frequency representations in fields A, AI, P, and VP are interconnected. A single isotope injection generally produced multiple patches of labeling within each of several cortical fields. Within AI, projections from contralateral fields A and AI and from ipsilateral fields A and P terminate in patches which are often elongated in a direction parallel to the low-to-high best-frequency gradient. A divergence in the projections from one field upon another is apparent in many experiments. Within fields A, AI, P, and VP, patches of label are distributed along a band of cortex oriented parallel to isofrequency lines.

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