The Insula of Reil Revisited: Multiarchitectonic Organization in Macaque Monkeys

The insula of Reil represents a large cortical territory buried in the depth of the lateral sulcus and subdivided into 3 major cytoarchitectonic domains: agranular, dysgranular, and granular. The present study aimed at reinvestigating the architectonic organization of the monkey's insula using multiple immunohistochemical stainings (parvalbumin, PV; nonphosphorylated neurofilament protein, with SMI-32; acetylcholinesterase, AChE) in addition to Nissl and myelin. According to changes in density and laminar distributions of the neurochemical markers, several zones were defined and related to 8 cytoarchitectonic subdivisions (Ia1-Ia2/Id1-Id3/Ig1-Ig2/G). Comparison of the different patterns of staining on unfolded maps of the insula revealed: 1) parallel ventral to dorsal gradients of increasing myelin, PV- and AChE-containing fibers in middle layers, and of SMI-32 pyramidal neurons in supragranular layers, with merging of dorsal and ventral high-density bands in posterior insula, 2) definition of an insula "proper” restricted to two-thirds of the "morphological” insula (as bounded by the limiting sulcus) and characterized most notably by lower PV, and 3) the insula proper is bordered along its dorsal, posterodorsal, and posteroventral margin by a strip of cortex extending beyond the limits of the morphological insula and continuous architectonically with frontoparietal and temporal opercular areas related to gustatory, somatosensory, and auditory modalitie

Central auditory processing: integration with other systems

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46536/1/221_2003_Article_1715.pd

The projection from auditory cortex to cochlear nucleus in guinea pigs: an in vivo anatomical and in vitro electrophysiological study

Previous anatomical experiments have demonstrated the existence of a direct, bilateral projection from the auditory cortex (AC) to the cochlear nucleus (CN). However, the precise relationship between the origin of the projection in the AC and the distribution of axon terminals in the CN is not known. Moreover, the influence of this projection on CN principal cells has not been studied before. The aim of the present study was two-fold. First, to extend the anatomical data by tracing anterogradely the distribution of cortical axons in the CN by means of restricted injections of biotinylated dextran amine (BDA) in physiologically characterized sites in the AC. Second, in an in vitro isolated whole brain preparation (IWB), to assess the effect of electrical stimulation of the AC on CN principal cells from which intracellular recordings were derived. BDA injections in the tonotopically organized primary auditory cortex and dorsocaudal auditory field at high and low best frequency (BF) sites resulted in a consistent axonal labeling in the ipsilateral CN of all injected animals. In addition, fewer labeled terminals were observed in the contralateral CN, but only in the animals subjected to injections in low BF region. The axon terminal fields consisting of boutons en passant or terminaux were found in the superficial granule cell layer and, to a smaller extent, in the three CN subdivisions. No axonal labeling was seen in the CN as result of BDA injection in the secondary auditory area (dorsocaudal belt). In the IWB, the effects of ipsilateral AC stimulation were tested in a population of 52 intracellulary recorded and stained CN principal neurons, distributed in the three CN subdivisions. Stimulation of the AC evoked slow late excitatory postsynaptic potentials (EPSPs) in only two cells located in the dorsal CN. The EPSPs were induced in a giant and a pyramidal cell at latencies of 20ms and 33ms, respectively, suggesting involvement of polysynaptic circuits. These findings are consistent with anatomical data showing sparse projections from the AC to the CN and indicate a limited modulatory action of the AC on CN principal cell

Effects of dorsolateral prefrontal cortex lesion on motor habit and performance assessed with manual grasping and control of force in macaque monkeys.

In the context of an autologous adult neural cell ecosystem (ANCE) transplantation study, four intact adult female macaque monkeys underwent a unilateral biopsy of the dorsolateral prefrontal cortex (dlPFC) to provide the cellular material needed to obtain the ANCE. Monkeys were previously trained to perform quantitative motor (manual dexterity) tasks, namely, the "modified-Brinkman board" task and the "reach and grasp drawer" task. The aim of the present study was to extend preliminary data on the role of the prefrontal cortex in motor habit and test the hypothesis that dlPFC contributes to predict the grip force required when a precise level of force to be generated is known beforehand. As expected for a small dlPFC biopsy, neither the motor performance (score) nor the spatiotemporal motor sequences were affected in the "modified-Brinkman board" task, whereas significant changes (mainly decreases) in the maximal grip force (force applied on the drawer knob) were observed in the "reach and grasp drawer" task. The present data in the macaque monkey related to the prediction of grip force are well in line with the previous fMRI data reported for human subjects. Moreover, the ANCE transplantation strategy (in the case of stroke or Parkinson's disease) based on biopsy in dlPFC does not generate unwanted motor consequences, at least as far as motor habit and motor performance are concerned in the context of a sequential grasping a small objects, which does not require the development of significant force levels

Gigantism in unique biogenic magnetite at the Paleocene-Eocene Thermal Maximum

We report the discovery of exceptionally large biogenic magnetite crystals in clay-rich sediments spanning the Paleocene-Eocene Thermal Maximum (PETM) in a borehole at Ancora, New Jersey. Aside from previously-described abundant bacterial magnetofossils, electron microscopy reveals novel spearhead-like and spindle-like magnetite up to 4 μm long and hexaoctahedral prisms up to 1.4 μm long. Similar to magnetite produced by magnetotactic bacteria, these single-crystal particles exhibit chemical composition, lattice perfection, and oxygen isotopes consistent with an aquatic origin. Electron holography indicates single-domain magnetization despite their large crystal size. We suggest that the development of a thick suboxic zone with high iron bioavailability – a product of dramatic changes in weathering and sedimentation patterns driven by severe global warming – drove diversification of magnetite-forming organisms, likely including eukaryotes

A case of polymicrogyria in macaque monkey: impact on anatomy and function of the motor system

Background: Polymicrogyria is a malformation of the cerebral cortex often resulting in epilepsy or mental retardation. It remains unclear whether this pathology affects the structure and function of the corticospinal (CS) system. The anatomy and histology of the brain of one macaque monkey exhibiting a spontaneous polymicrogyria (PMG monkey) were examined and compared to the brain of normal monkeys. The CS tract was labelled by injecting a neuronal tracer (BDA) unilaterally in a region where low intensity electrical microstimulation elicited contralateral hand movements (presumably the primary motor cortex in the PMG monkey). Results: The examination of the brain showed a large number of microgyri at macro- and microscopic levels, covering mainly the frontoparietal regions. The layered cortical organization was locally disrupted and the number of SMI-32 stained pyramidal neurons in the cortical layer III of the presumed motor cortex was reduced. We compared the distribution of labelled CS axons in the PMG monkey at spinal cervical level C5. The cumulated length of CS axon arbors in the spinal grey matter was not significantly different in the PMG monkey. In the red nucleus, numerous neurons presented large vesicles. We also assessed its motor performances by comparing its capacity to execute a complex reach and grasp behavioral task. The PMG monkey exhibited an increase of reaction time without any modification of other motor parameters, an observation in line with a normal CS tract organisation. Conclusion: In spite of substantial cortical malformations in the frontal and parietal lobes, the PMG monkey exhibits surprisingly normal structure and function of the corticospinal system

Combined with anti‐Nogo‐A antibody treatment, BDNF did not compensate the extra deleterious motor effect caused by large size cervical cord hemisection in adult macaques

In spinal cord injured adult mammals, neutralizing the neurite growth inhibitor Nogo‐A with antibodies promotes axonal regeneration and functional recovery, although axonal regeneration is limited in length. Neurotrophic factors such as BDNF stimulate neurite outgrowth and protect axotomized neurons. Can the effects obtained by neutralizing Nogo‐A, inducing an environment favorable for axonal sprouting, be strengthened by adding BDNF? A unilateral incomplete hemicord lesion at C7 level interrupted the main corticospinal component in three groups of adult macaque monkeys: control monkeys (n = 6), anti‐Nogo‐A antibody‐treated monkeys (n = 7), and anti‐Nogo‐A antibody and BDNF‐treated monkeys (n = 5). The functional recovery of manual dexterity was significantly different between the 3 groups of monkeys, the lowest in the control group. Whereas the anti‐Nogo‐A antibody‐treated animals returned to manual dexterity performances close to prelesion ones, irrespective of lesion size, both the control and the anti‐Nogo‐A/BDNF animals presented a limited functional recovery. In the control group, the limited spontaneous functional recovery depended on lesion size, a dependence absent in the combined treatment group (anti‐Nogo‐A antibody and BDNF). The functional recovery in the latter group was significantly lower than in anti‐Nogo‐A antibody‐treated monkeys, although the lesion was larger in three out of the five monkeys in the combined treatment group

Folding-competent and folding-defective forms of Ricin A chain have different fates following retrotranslocation from the endoplasmic reticulum

We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTAΔ), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate

Short-term effects of unilateral lesion of the primary motor cortex (M1) on ipsilesional hand dexterity in adult macaque monkeys

Although the arrangement of the corticospinal projection in primates is consistent with a more prominent role of the ipsilateral motor cortex on proximal muscles, rather than on distal muscles involved in manual dexterity, the role played by the primary motor cortex on the control of manual dexterity for the ipsilateral hand remains a matter a debate, either in the normal function or after a lesion. We, therefore, tested the impact of permanent unilateral motor cortex lesion on the manual dexterity of the ipsilateral hand in 11 macaque monkeys, within a time window of 60 days post-lesion. For comparison, unilateral reversible pharmacological inactivation of the motor cortex was produced in an additional monkey. Manual dexterity was assessed quantitatively based on three motor parameters derived from two reach and grasp manual tasks. In contrast to the expected dramatic, complete deficit of manual dexterity of the contralesional hand that persists for several weeks, the impact on the manual dexterity of the ipsilesional hand was generally moderate (but statistically significant) and, when present, lasted less than 20 days. Out of the 11 monkeys, only 3 showed a deficit of the ipsilesional hand for 2 of the 3 motor parameters, and 4 animals had a deficit for only one motor parameter. Four monkeys did not show any deficit. The reversible inactivation experiment yielded results consistent with the permanent lesion data. In conclusion, the primary motor cortex exerts a modest role on ipsilateral manual dexterity, most likely in the form of indirect hand postural control