Beneficial effect of risedronate for preventing recurrent hip fracture in the elderly Japanese women.

SUMMARY: A 36-month observational study compared the incidence of unaffected side hip fracture in Japanese female osteoporosis patients with a history of hip fracture between 173 patients receiving risedronate and 356 risedronate-untreated controls. New hip fractures were significantly less frequent in the risedronate group, suggesting a preventive effect in high-risk patients. INTRODUCTION: The purpose of this study was to investigate the preventive effect of risedronate on second hip fracture immediately following a first hip fracture in Japanese female osteoporosis patients with unilateral hip fracture. METHODS: We conducted a prospective matched cohort study in 184 patients treated with risedronate and 445 patients not receiving risedronate after discharge from hospital. Both groups were followed-up for 36 months, and the incidence of unaffected side hip fracture and the frequency of adverse events were assessed. RESULTS: Efficacy could be investigated in 173 patients from the risedronate group and 356 patients from the control group. Hip fracture was detected in 5 and 32 patients, respectively. Kaplan-Meier estimates of the 36-month fracture incidence were 4.3% in the risedronate group and 13.1% in the control group (P = 0.010, log-rank test). The hazard ratios (95% confidence intervals) obtained by univariate and multivariate analysis were 0.310 (0.121-0.796) and 0.218 (0.074-0.639), respectively, indicating a significantly lower incidence of unaffected side hip fracture in the risedronate group. Adverse events occurred in 38 patients (48 events) from the risedronate group and 94 patients (108 events) from the control group, with serious adverse events in 21 patients (26 events) and 78 patients (88 events), respectively. CONCLUSIONS: No significant differences were observed between the two groups. The incidence of unaffected side hip fracture was significantly lower in the risedronate group. Accordingly, risedronate may have a preventive effect on hip fracture in high-risk Japanese female osteoporosis patients for fracture with a history of unilateral hip fracture.

Adiponectin regulates functions of gingival fibroblasts and periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Adiponectin is a cytokine constitutively produced by adipocytes and exhibits multiple biological functions by targeting various cell types. However, the effects of adiponectin on primary gingival fibroblasts and periodontal ligament cells are still unexplored. Therefore, we investigated the effects of adiponectin on gingival fibroblasts and periodontal ligament cells. MATERIAL AND METHODS: The expression of adiponectin receptors (AdipoR1 and AdipoR2) on human gingival fibroblasts (HGFs), mouse gingival fibroblasts (MGFs) and human periodontal ligament (HPDL) cells was examined using RT-PCR and western blotting. HGFs and MGFs were stimulated with interleukin (IL)-1ß in the presence or absence of adiponectin, and the expression of IL-6 and IL-8 at both mRNA and protein levels was measured by real-time PCR and ELISA, respectively. Furthermore, small interfering RNAs (siRNAs) in MGFs were used to knock down the expression of mouse AdipoR1 and AdipoR2. The effects of adiponectin on the expression of alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2) genes were evaluated by real-time PCR. Mineralized nodule formation of adiponectin-treated HPDL cells was revealed by Alizarin Red staining. RESULTS: AdipoR1 and AdipoR2 were expressed constitutively in HGFs, MGFs and HPDL cells. Adiponectin decreased the expression of IL-6 and IL-8 in IL-1ß-stimulated HGFs and MGFs. AdipoR1 siRNA in MGFs revealed that the effect of adiponectin on reduction of IL-6 expression was potentially mediated via AdipoR1. Adiponectin-treated HPDL cells promoted the expression of ALP and Runx2 mRNAs and up-regulated ALP activity. Furthermore, adiponectin enhanced mineralized nodule formation of HPDL cells. CONCLUSION: Our observations demonstrate that adiponectin exerts anti-inflammatory effects on HGFs and MGFs, and promotes the activities of osteoblastogenesis of HPDL cells. We conclude that adiponectin has potent beneficial functions to maintain the homeostasis of periodontal health, improve periodontal lesions, and contribute to wound healing and tissue regeneration.

Transient and persistent phosphorylation of AMPA-type glutamate receptor subunits in cerebellar Purkinje cells.

We generated a polyclonal antibody, 12P3, specifically recognizing rat AMPA-type glutamate receptor (GluR) subunits phosphorylated at Ser-696 of GluR2 or at the homologous sites in GluR1, GluR3, and GluR4. Using 12P3, we demonstrate that a brief exposure of a rat cerebellar slice to AMPA leads to transient phosphorylation of the GluR subunits in Purkinje cell dendrites. Persistent phosphorylation over 30 min was obtained when exposure to AMPA was preceded by a 15 min perfusion of the slice with 8-bromo-cGMP, dibutyryl-cGMP, or calyculin A but not phorbol 12,13-diacetate. These results indicate that Ser-696 of GluR2, or the corresponding sites in other AMPA receptor subunits, is a specific site at which phosphorylation takes place when AMPA-type GluRs are activated by agonists, especially under the influence of certain second messenger activities.

Activation of adenosine receptor on gingival fibroblasts.

CD73 (ecto-5'-nucleotidase) on human gingival fibroblasts plays a role in the regulation of intracellular cAMP levels through the generation of adenosine, which subsequently activates adenosine receptors. In this study, we examined the involvement of ecto-adenosine deaminase, which can be anchored to CD26 on human gingival fibroblasts, in metabolizing adenosine generated by CD73, and thus attenuating adenosine receptor activation. Ecto-adenosine deaminase expression on fibroblasts could be increased by pre-treatment with a lysate of Jurkat cells, a cell line rich in cytoplasmic adenosine deaminase. Interestingly, the cAMP response to adenosine generated from 5'-AMP via CD73 and the ability of 5'-AMP to induce hyaluronan synthase 1 mRNA were significantly decreased by the pre-treatment of fibroblasts with Jurkat cell lysate. This inhibitory effect was reversed by the specific adenosine deaminase inhibitor. These results suggest that ecto-adenosine deaminase metabolizes CD73-generated adenosine and regulates adenosine receptor activation.

Connections between anterior inferotemporal cortex and superior temporal sulcus regions in the macaque monkey.

We examined the connections between the anterior inferotemporal cortex and the superior temporal sulcus (STS) in the macaque monkey by injecting Phaseolus vulgaris leucoagglutinin (PHA-L) or wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the dorsoanterior and ventroanterior subdivisions of TE (TEad and TEav, respectively) and observing the labeled terminals and cell bodies in STS. We found a clear dichotomy in the connections of the rostral part of STS: the injections into TEad resulted in a dense distribution of labeled terminals and cell bodies in the upper bank of rostral STS, whereas labeling was confined to the lower bank and fundus of rostral STS after injections into TEav. The distribution of labeling in the rostral STS was discontinuous from the distribution of labeling surrounding the injection sites: the lower bank of the rostral STS was spared from labeling in the TEad injection cases, and TEad had only sparse distribution in the TEav injection cases. These results revise the classical view that the lower bank of rostral STS is connected with TE, whereas the upper bank of rostral STS is connected with the parietal, prefrontal, and superior temporal regions (Seltzer and Pandya, 1978, 1991, 1994). The upper bank of the rostral STS is called the superior temporal polysensory area (STP), because it was previously found that neurons there respond to auditory, somatosensory, and visual stimuli. The present results thus suggest that the polymodal representation in STP interacts more with information processing in TEad than TEav. It is also suggested that the information processing in the ventral bank of the rostral STS is distinct from that in TEad, and the former more directly interacts with TEav than TEad.

Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development.

Climbing fiber (CF) synapse formation onto cerebellar Purkinje cells (PCs) is critically dependent on the synaptogenesis from parallel fibers (PFs), the other input to PCs. Previous studies revealed that deletion of the glutamate receptor delta2 subunit (GluRdelta2) gene results in persistent multiple CF innervation of PCs with impaired PF synaptogenesis, whereas mutation of the metabotropic glutamate receptor subtype 1 (mGluR1) gene causes multiple CF innervation with normal PF synaptogenesis. We demonstrate that atypical CF-mediated EPSCs (CF-EPSCs) with slow rise times and small amplitudes coexisted with typical CF-EPSCs with fast rise times and large amplitudes in PCs from GluRdelta2 mutant cerebellar slices. CF-EPSCs in mGluR1 mutant and wild-type PCs had fast rise times. Atypical slow CF responses of GluRdelta2 mutant PCs were associated with voltage-dependent Ca(2+) signals that were confined to PC distal dendrites. In the wild-type and mGluR1 mutant PCs, CF-induced Ca(2+) signals involved both proximal and distal dendrites. Morphologically, CFs of GluRdelta2 mutant mice extended to the superficial regions of the molecular layer, whereas those of wild-type and mGluR1 mutant mice did not innervate the superficial one-fifth of the molecular layer. It is therefore likely that surplus CFs of GluRdelta2 mutant mice form ectopic synapses onto distal dendrites, whereas those of wild-type and mGluR1 mutant mice innervate proximal dendrites. These findings suggest that GluRdelta2 is required for consolidating PF synapses and restricting CF synapses to the proximal dendrites, whereas the mGluR1-signaling pathway does not affect PF synaptogenesis but is involved in eliminating surplus CF synapses at the proximal dendrites.

Mitochondrial protease Omi/HtrA2 enhances caspase activation through multiple pathways.

Omi/HtrA2 is a mitochondrial serine protease that is released into the cytosol during apoptosis and promotes cytochrome c (Cyt c)dependent caspase activation by neutralizing inhibitor of apoptosis proteins (IAPs) via its IAP-binding motif. The protease activity of Omi/HtrA2 also contributes to the progression of both apoptosis and caspase-independent cell death. In this study, we found that wild-type Omi/HtrA2 is more effective at caspase activation than a catalytically inactive mutant of Omi/HtrA2 in response to apoptotic stimuli, such as UV irradiation or tumor necrosis factor. Although similar levels of Omi/HtrA2 expression, XIAP-binding activity, and Omi/HtrA2 mitochondrial release were observed among cells transfected with catalytically inactive and wild-type Omi/HtrA2 protein, XIAP protein expression after UV irradiation was significantly reduced in cells transfected with wild-type Omi/HtrA2. Recombinant Omi/HtrA2 was observed to catalytically cleave IAPs and to inactivate XIAP in vitro, suggesting that the protease activity of Omi/HtrA2 might be responsible for its IAP-inhibiting activity. Extramitochondrial expression of Omi/HtrA2 indirectly induced permeabilization of the outer mitochondrial membrane and subsequent Cyt c-dependent caspase activation in HeLa cells. These results indicate that protease activity of Omi/HtrA2 promotes caspase activation through multiple pathways.

Early and progressive accumulation of reactive microglia in the Huntington disease brain.

Microglia may contribute to cell death in neurodegenerative diseases. We studied the activation of microglia in affected regions of Huntington disease (HD) brain by localizing thymosin beta-4 (Tbeta4), which is increased in reactive microglia. Activated microglia appeared in the neostriatum, cortex, and globus pallidus and the adjoining white matter of the HD brain, but not in control brain. In the striatum and cortex, reactive microglia occurred in all grades of pathology, accumulated with increasing grade, and grew in density in relation to degree of neuronal loss. The predominant morphology of activated microglia differed in the striatum and cortex. Processes of reactive microglia were conspicuous in low-grade HD, suggesting an early microglia response to changes in neuropil and axons and in the grade 2 and grade 3 cortex, were aligned with the apical dendrites of pyramidal neurons. Some reactive microglia contacted pyramidal neurons with huntingtin-positive nuclear inclusions. The early and proximate association of activated microglia with degenerating neurons in the HD brain implicates a role for activated microglia in HD pathogenesis.

The inferior colliculopontine neurons of the cat in relation to other collicular descending neurons.

Cells of origin of the pontine afferents from the inferior colliculus (IC) of cats have been identified by means of retrograde axonal transport of horseradish peroxidase (HRP). Following injections of HRP in the pontine nuclei, many labeled neurons were found ipsilaterally in the caudal parts of the external and pericentral nuclei, while a few cells were found in the central nucleus. Additional neurons occurred in the nuclei of the middle and rostral parts. This organization contrasts with that of other collicular descending systems. Thus, neurons projecting to the superior olivary complex and cochlear nuclei were found predominantly in the central nucleus bilaterally. In the external nucleus labeled cells tended to be distributed in the middle to rostral regions, but they were few in number in the caudal part. Since the locations of IC-pontine neurons are found to be different from those of other IC descending neurons, it may be assumed that the IC-pontine system does not share common functional properties with the other collicular descending neurons. Functional aspects of the IC-pontine neurons are discussed, with a comment on a pathway for the transmission of auditory impulses to the midvermal area of the cerebellum.

Cell bodies of origin of reticular projections from the superior colliculus in the cat: an experimental study with the use of horseradish peroxidase as a tracer.

By use of the retrograde axonal transport of horseradish peroxidase (HRP), the projection from the superior colliculus (SC) to the brain stem reticular formation (RF) was investigated in the cat. A 0.2-0.5 microliter of a 50% suspension of Sigma VI HRP was injected stereotactically in various portions of the pontomedullary RF, and, as a control to the injection to the RF, in the inferior olive or in the spinal cord. Labeled cells were found within and deep to the intermediate gray layer of the SC in the cats which survived for two or three days after HRP injection. The number of the labeled cells varied, according to the difference in the site of injection and the amount of injected HRP. About 400 labeled cells in twenty 50-micron sections, taken every fifth of the SC, occurred throughout its rostrocaudal extent, particularly in the case where the medial portion of the border zone of the nucleus reticularis pontis oralis and caudalis (R.p.o.-R.p.c. zone) or the border zone of the nucleus reticularis pontis caudalis and the gigantocellularis (R.p.c.-R.gc. zone) was heavily stained after three days of survival period. From 10 to 15% of these labeled cells were large in size (more than 40 micron in diameter), 20-30% were medium sized and the rest (60-70%) were small (10-25 micron). On the other hand, when HRP was placed in the inferior olive only eight cells were labeled in the SC, seven of which were small and medium-sized. When HRP was injected in the gray matter of C1-C3 level of the spinal cord, a total of 70 tectal cells (14, 42, and 14 were large, medium, and small cells, respectively) were observed to be labeled. The findings of the tectoreticular neurons are discussed and compared with those of the tectoolivary and the tectospinal neurons. Thus the three kinds of tectal neurons are located within and deep to the intermediate gray layer. The number of the labeled cells and the percentages of the collicular neurons of different sizes are obviously different among the three different projections. Topographic correlations between the SC and the RF could not be discerned in the present materials. These results were discussed in relation to possible influences of the tectoreticular neurons upon the extraocular and the spinal motoneurons.

Projections from the pontine nuclei proper and reticular tegmental nucleus onto the cerebellar cortex in the cat. An autoradiographic study.

After injections of 0.5 microliter of tritiated leucine and/or proline into various parts of the pontine nuclei proper or the pontine tegmental reticular nucleus (N.r.t.) of 34 cats, labeled terminals of pontocerebellar fibers were found in the cerebellar cortex. Fibers from the pontine nuclei and N.r.t. terminate as mossy fibers in the granular layer of the cerebellum, and no evidence is obtained of labeled fibers in the molecular layer. The pontocerebellar projection is, in general, bilateral with a contralateral preponderance, and a complex organization has been shown to exist in the cat. Clear evidence of divergence of this projection from a small pontine area has been demonstrated. Thus, the dorsolateral nucleus has a heavy projection to lobule VII, besides modest projections to lobules VI, VIII, and IX, crus I and II, paraflocculus, and paramedian lobule. On the other hand, a particular cerebellar region receives afferent fibers from several pontine regions, confirming previous HRP studies. For example, lobule VII receives heavy projections from parts of the dorsolateral, peduncular, and paramedian nuclei, less heavy projections from the lateral part of the lateral nucleus, and some from other parts of the pontine nuclei. This is a convergent feature of the pontocerebellar projections. In addition, small adjoining areas within a pontine subdivision have different patterns of cerebellar projections, shwing preferential sites of terminations. This suggests some degree of localization within the pontine nuclei. The cerebellar projection from the N.r.t. shows an essentially similar organization as the projection from the pontine nuclei proper, an apparent difference being only that the former is more extensive in the fields of termination than the latter. Some evidence for a parasagittal termination of pontocerebellar projections to the paramedian lobule has been found in this study. However, this is not as clear-cut as such patterns in the cerebellar projections from the spinal cord, cuneate nucleus, and lateral reticular nucleus shown recently in rat and cat.

Connections of the dorsal zone of cat auditory cortex.

The present study examined the anatomic connections of the dorsal zone of cat auditory cortex (DZ). The DZ was discriminated physiologically from the primary auditory field (AI) on the basis of neuronal responses with long latency and broad or multipeaked tuning curves. Wheat germ agglutinin-horseradish peroxidase was then injected either by pressure or iontophoretically. The thalamocortical and corticothalamic connections of the DZ were visualized by the presence of retrogradely labeled neurons and anterogradely labeled terminal fields in the thalamus; ipsilateral corticocortical projections from other cortical fields were visualized by the presence of retrogradely labeled cells. Injections of tracer into the DZ retrogradely labeled cells mainly in the lateral division of posterior complex (Po) and in the dorsal division (MGd) of the medial geniculate body (MGB); fewer labeled cells were found in the ventral (MGv) and medial (MGm) divisions of the MGB and in the suprageniculate nucleus. The DZ projection to Po, MGv, and MGd was heavy and was more diffuse than the reciprocal thalamocortical projection; the projection to MGm was light. The corticothalamic terminations and thalamocortical cells projecting to the same part of the DZ were not superimposed rigidly. The DZ received cortical projections from AI and from the second, anterior, and posterior auditory fields, and there were strong intra-DZ connections. Together with the physiological findings, the present results suggest that the DZ is a potentially separate auditory field from AI and is likely to be involved in both temporal and spectral integration of acoustic information.

Projections from the parabigeminal nucleus to the dorsal lateral geniculate nucleus in the tree shrew Tupaia glis.

The parabigeminal nucleus receives its major input from the superficial layers of the superior colliculus via the tectoparabigeminal projection. An extensive reciprocal parabigeminotectal pathway has also been observed. This close connectional association between the superficial gray and the parabigeminal nucleus is reflected in the collicularlike response characteristics of parabigeminal neurons (see Sherk: Brain Res. 145:375-379, '78, J. Neurophysiol. 42:1640-1655, 1656-1668, '79a,b, for review). Further documentation of the connectional relationship between the superior colliculus and the parabigeminal nucleus comes from the present data. Thus, our retrograde and anterograde transport findings reveal an extensive projection from the parabigeminal nucleus to layers 3 and 6 and several interlaminar zones of the contralateral dorsal lateral geniculate nucleus. These same layers and interlaminar zones receive tectogeniculate axons and have been shown to contain small cells that project to layers 1 and 3 of area 17. In addition to the distribution of parabigeminal axons to tectally innervated, small-celled zones, considerable parabigeminal input also reaches layers 1 and 5 of the tree shrew lateral geniculate nucleus. Each of these layers is the ipsilaterally (i.e., retinal) innervated component of a matched pair (layers 1 and 2 are considered magnocellular, while 4 and 5 are parvicellular), and it has been shown that layer 1 projects to lamina IVa of area 17, while layer 5 projects to lamina IVB. When the total distribution of parabigeminogeniculate axons is considered, it is apparent that the cells of origin of each of the major (small-celled, parvi- and magnocellular) geniculocortical channels receives parabigeminal input. Such an extensive distribution of parabigeminal axons within the lateral geniculate nucleus suggests that the information they convey might play an important role in geniculocortical function(s).

Patchy and laminar terminations of medial geniculate axons in monkey auditory cortex.

The object of this study was to identify the terminal distributions of thalamocortical axons arising in chemically characterized subdivisions of the medial geniculate complex. Large injections of wheat germ agglutinin-conjugated horseradish peroxidase or small injections of Phaseolus vulgaris leucoagglutinin were made in the medial geniculate complex of Macaca fuscata. The terminal distributions of labeled axons in the cortex were correlated with auditory cortical fields demonstrable by different intensities of immunoreactivity for parvalbumin. Fibers from the ventral nucleus terminated mainly in layer IV and deep portion of layer III (IIIB), with additional terminations in layers I-IIIA and in layer VI. In layers IIIB-IV, a major terminal plexus was formed by a small number of dense patches, 300-500 microns in diameter, surrounded by smaller satellite patches. The patches conformed to a similarly lobulated pattern of parvalbumin fiber immunoreactivity. Terminations of some individually labeled thalamocortical fibers were restricted to a single patch, whereas others innervated more than one patch by collateral branches. Fibers from the dorsal nuclei ending in areas of less dense parvalbumin immunoreactivity surrounding the primary auditory cortex formed much larger terminal patches centered largely in layer IIIB. Fibers from the magnocellular nucleus had relatively few terminal branches but innervated extremely wide areas by collaterals of single axons. Two types of axons arose from the magnocellular nucleus, one terminating preferentially in middle cortical layers and the other exclusively in layer I. These may arise respectively from parvalbumin- and calbindin-immunoreactive cell populations in the magnocellular nucleus.

The trigemino-olivary projection in the cat: contributions of individual subnuclei.

Anterograde autoradiographic methods were used to determine the projection of the principal sensory trigeminal nucleus and of each of the three spinal trigeminal subnuclei to the inferior olivary complex in the cat. Our data reveal that the principal sensory trigeminal nucleus does not contribute to the trigemino-olivary pathway. Each spinal trigeminal subnucleus has a unique contribution to this pathway: pars oralis projects sparsely to the border between the dorsal accessory and principal olives (DAO-PO), pars interpolaris projects mostly to the rostral medial DAO, and pars caudalis projects mostly to the rostral medial part of the ventral leaf of PO and slightly to the caudal medial accessory olive. In the light of recent physiological and anatomical findings, our data indicate that information from each spinal trigeminal subnucleus reaches a different segment of the contralateral inferior olivary complex, which in turn distributes differentially to the cerebellar cortex.

Differential expression of gamma-aminobutyric acid type B receptor-1a and -1b mRNA variants in GABA and non-GABAergic neurons of the rat brain.

To understand the heterogeneity of gamma-aminobutyric acid type B receptor (GABABR)-mediated events, we investigated expression of GABABR1a and 1b mRNA variants in GABA and non-GABAergic neurons of the rat central nervous system (CNS), by using nonradioactive in situ hybridization histochemistry and, in combination with GABA immunocytochemistry, double labeling. In situ hybridization with a pan probe, which recognizes a common sequence of both GABABR1a and GABABR1b mRNA variants, demonstrated widespread expression of GABABR1 mRNA at various levels in the CNS. Both GABABR1a and GABABR1b were expressed in the neocortex, hippocampus, dorsal thalamus, habenula, and septum, but only GABABR1a was detected in cerebellar granule cells, in caudate putamen, and most hindbrain structures. A majority of GABA neurons in cerebral cortex showed hybridization signals for both GABABR1a and GABABR1b, whereas those in most subcortical structures expressed either or neither of the two. GABA neurons in thalamic reticular nucleus and caudate putamen hybridized primarily for GABABR1a. Purkinje cells in the cerebellar cortex expressed predominantly GABABR1b. GABA neurons in dorsal lateral geniculate nucleus did not display significant levels of either GABABR1a or GABABR1b mRNAs. These data suggested widespread availability of GABABR-mediated inhibition in the CNS. The differential but overlapping expression of GABABR1 mRNA variants in different neurons and brain structures may contribute to the heterogeneity of GABABR-mediated inhibition. Some GABA neurons possessed, but others might lack the molecular machinery for GABABR-mediated disinhibition, autoinhibition, or both.

Tonotopic organization of auditory cortical fields delineated by parvalbumin immunoreactivity in macaque monkeys.

Tonotopic maps, obtained from single and multi-unit recordings in the primary and surrounding areas of the auditory cortex, were related to chemoarchitecture of the supratemporal plane, as delineated by immunoreactivity for parvalbumin. Neurons in the central core were sharply tuned and formed two complete tonotopic representations corresponding to the primary auditory area (AI) and the rostral (R) area. High frequencies were represented posteriorly in AI and anteriorly in R, the representation reversing in the anterior part of the core. Neurons in regions of less dense immunostaining previously described as lateral (L) and posteromedial (P-m) fields, showed broader frequency tuning. Two tonotopic representations were found in L: in an anterolateral (AL) field, corresponding to a field previously reported by others, high frequencies were represented anteriorly and low frequencies posteriorly; in a posterolateral field (PL) the trend reversed. There was a further reversal on entering P-m from the high frequency representation in PL and progressively lower frequencies tended to be represented more medially in P-m, but P-m may contain two representations reported by others. Neurons in the previously described anteromedial (A-m) and medial (M) fields of weaker immunostaining, were even more broadly tuned. A tonotopic progression from low frequency representation posteriorly to high frequency representation anteriorly was observed in the medial field. Frequency representation in A-m remains uncertain. No tonotopic representation could be demonstrated with the stimuli used in the zones of very weak parvalbumin immunostaining outside AL, PL, P-m, A-m, and M. The properties of neurons in the core and surrounding zones are likely to reflect inputs from the ventral and dorsal medial geniculate nuclei, respectively. The fields outside the core seem to be the starting points for separate streams of auditory corticocortical connections passing into association cortex.

Projection of the mammalian superior colliculus upon the dorsal lateral geniculate nucleus: organization of tectogeniculate pathways in nineteen species.

Anterograde and retrograde transport methods have been used to analyze the projection of the superior colliculus upon the dorsal lateral geniculate nucleus in 19 mammalian species. Our retrograde findings reveal that tectogeniculate neurons are relatively small, and lie dorsally within the superficial gray. These small tectogeniculate neurons are spatially related to a dense tier of W-cell retinal input. Our anterograde tracing results show that tectogeniculate axons are visuotopically distributed to small-celled regions of the lateral geniculate in all nineteen species. In the majority of these species, the small-celled, tectally innervated regions of the lateral geniculate lie adjacent to the optic tract and contain W-cell-like neurons. Our findings suggest that neuroanatomical demonstration of the tectogeniculate projection is a relatively simple and straightforward way of revealing regions of the lateral geniculate which contain W-cells. This is true even in species in which the lateral geniculate lacks obvious cellular laminae, and in regions of the lateral geniculate where W-cells are few in number. The present data are especially interesting in light of the cortical projections of tectally innervated, small-celled regions of the lateral geniculate to the patches or puffs within layer III of area 17. Since these regions of small-celled geniculocortical axons are co-extensive with zones ("blobs") rich in cytochrome oxidase, it might be that information carried over the tectogeniculate circuitry plays an important role in the functions of the blob system.

The parabigeminogeniculate projection: connectional studies in eight mammals.

Anterograde and retrograde tracing methods have been used to analyze the origin and distribution of parabigeminogeniculate axons in the gray squirrel, the gopher, the rat, the opossum, the cat, the greater bushbaby, the squirrel monkey and the macaque monkey. Our findings reveal that parabigeminogeniculate axons most heavily innervate regions of the lateral geniculate that are also targeted by axons arising from the superior colliculus (tectogeniculate). These geniculate layers and zones of parabigeminal and tectal overlap contain small cells, and in several species are associated with the small W cell retino-geniculocortical pathway. In addition to the dense input to small-celled layers and zones, parabigeminal axons in several species also innervate regions of the lateral geniculate nucleus that are relatively free of tectogeniculate axons and that are associated with the medium (X) and large (Y) cell streams. Finally, our data reveal that the laterality of parabigeminogeniculate pathways varies across mammals, being primarily crossed in the gray squirrel, the gopher, the rat, and the opossum, bilateral in the cat, and primarily ipsilateral in the three primates.

Subdivisions of macaque monkey auditory cortex revealed by calcium-binding protein immunoreactivity.

The aim of this investigation was to characterize auditory areas of the primate cerebral cortex on the basis of chemoarchitecture. Cortical areas of the supratemporal plane were delineated in Macaca fuscata (M. fuscata) by immunocytochemical staining for parvalbumin, staining for cytochrome oxidase, examination of cyto- and myeloarchitecture, and retrograde tracing of corticocortical connections. Comparative observations were made on Macaca fascicularis (M. fascicularis). Differential staining of fiber plexuses, probably of thalamic origin, identifies a central core zone of dense immunostaining and a surrounding zone of moderate-to-dense immunostaining composed of anteromedial, lateral, and posteromedial fields. Outside the second zone, there is a third anterolateral zone of weaker immunoreactivity, and, outside that zone, there is a fourth zone in which immunoreactivity is virtually absent. Differences in parvalbumin immunostaining in the auditory fields may reflect differences in relative contributions of thalamic inputs from parvalbumin-immunoreactive cells in the medial geniculate complex. The central core zone and the surrounding three fields can be correlated with major auditory fields previously defined by multiunit mapping and thalamocortical connectivity. The core zone contains a large principal field and an anterior extension. The pattern of corticocortical connections between these and adjoining fields suggests that the anteromedial, lateral, and posteromedial fields represent first steps in three streams of connections passing outward from auditory into association cortex. M. fuscata has an unusually large auditory cortex that is more deeply placed in the lateral sulcus in comparison to that of M. fascicularis. A small annectant gyrus provides a guide to the position of the primary auditory area.