Mediolateral Regions Research Articles

A cortico-basal ganglia-thalamo-cortical channel underlying short-term memory

Persistent activity underlying short-term memory encodes sensory information or instructs specific future movement and, consequently, has a crucial role in cognition. Despite extensive study, how the same set of neurons respond differentially to form selective persistent activity remains unknown. Here, we report that the cortico-basal ganglia-thalamo-cortical (CBTC) circuit supports the formation of selective persistent activity in mice. Optogenetic activation or inactivation of the basal ganglia output nucleus substantia nigra pars reticulata (SNr)-to-thalamus pathway biased future licking choice, without affecting licking execution. This perturbation differentially affected persistent activity in the frontal cortex and selectively modulated neural trajectory that encodes one choice but not the other. Recording showed that SNr neurons had selective persistent activity distributed across SNr, but with a hotspot in the mediolateral region. Optogenetic inactivation of the frontal cortex also differentially affected persistent activity in the SNr. Together, these results reveal a CBTC channel functioning to produce selective persistent activity underlying short-term memory.

Contraction level, but not force direction or wrist position, affects the spatial distribution of motor unit recruitment in the biceps brachii muscle.

Different motor units (MUs) in the biceps brachii (BB) muscle have been shown to be preferentially recruited during either elbow flexion or supination. Whether these different units reside within different regions is an open issue. In this study, we tested wheter MUs recruited during submaximal isometric tasks of elbow flexion and supination for two contraction levels and with the wrist fixed at two different angles are spatially localized in different BB portions. The MUs' firing instants were extracted by decomposing high-density surface electromyograms (EMG), detected from the BB muscle of 12 subjects with a grid of electrodes (4 rows along the BB longitudinal axis, 16 columns medio-laterally). The firing instants were then used to trigger and average single-differential EMGs. The average rectified value was computed separately for each signal and the maximal value along each column in the grid was retained. The center of mass, defined as the weighted mean of the maximal, average rectified value across columns, was then consdiered to assess the medio-lateral changes in the MU surface representation between conditions. Contraction level, but neither wrist position nor force direction (flexion vs. supination), affected the spatial distribution of BB MUs. In particular, higher forces were associated with the recruitment of BB MUs whose action potentials were represented more medially. Although the action potentials of BB MUs were represented locally across the muscle medio-lateral region, dicrimination between elbow flexion or supination seems unlikely from the surface representation of MUs action potentials.

Modal analysis of nanoindentation data, confirming that reduced bone turnover may cause increased tissue mineralization/elasticity.

It is widely believed that the activities of bone cells at the tissue scale not only govern the size of the vascular pore spaces (and hence, the amount of bone tissue available for actually carrying the loads), but also the characteristics of the extracellular bone matrix itself. In this context, increased mechanical stimulation (in mediolateral regions of human femora, as compared to anteroposterior regions) may lead to increased bone turnover, lower bone matrix mineralization, and therefore lower tissue modulus. On the other hand, resorption-only processes (in endosteal versus periosteal regions) may have the opposite effect. A modal analysis of nanoindentation data obtained on femurs from the Melbourne Femur Research Collection (MFRC) indeed confirms that bone is stiffer in endosteal regions compared to periosteal regions (E̅endost = 29.34 ± 0.75 GPa >E̅periost = 24.67 ± 1.63 GPa), most likely due to the aging-related increase in resorption modeling on endosteal surfaces resulting in trabecularization of cortical bone. The results also show that bone is stiffer along the anteroposterior direction compared the mediolateral direction (E̅anteropost = 28.89 ± 1.08 GPa >E̅mediolat = 26.03 ± 2.31 GPa), the former being aligned with the neutral bending axis of the femur and, thus, undergoing more resorption modeling and consequently being more mineralized.

Dynamic expression pattern of Hoxc8 during mouse early embryogenesis

The Hoxc8 expression pattern was examined in mouse embryos 7.5-12.5 days postcoitum (dpc) using whole-mount in situ hybridization and RT-PCR. The expression of Hoxc8 started between 7.5 and 8.5 dpc. A strong expression was detected in the ectoderm and mesoderm at 8.5 dpc. At 9.5 dpc, a distinct anterior boundary of Hoxc8 expression was established at the 10th and 16th somites in the neural tube and the paraxial mesoderm, respectively. This staggered expression pattern was maintained throughout the later stages. By 12.5 dpc, the forward progression of the Hoxc8 expression pattern was observed and the stain was weakened. In the ectoderm-derived neural tube, strong Hoxc8 expression was observed in the ventral horn and later in the ventral and mediolateral region of the mantle layer, indicating a possible association with the onset and progression of neural differentiation. In the case of the mesoderm-derivative cells, strong Hoxc8 expression was detected in the sclerotome on the way to the notochord and neural tube and mesonephros, suggesting a role of Hoxc8 in the formation of the vertebrae and ribs and the possible involvement in the differentiation into the kidney.

Cytological and transcriptional compartments in the cerebellum of the staggerer mouse

The cerebellum exhibits a uniform histo‐ and cyto‐architecture. However numerous anatomical and biochemical studies have suggested that the cerebellum is highly compartmentalized in the mediolateral and rostrocaudal axes. In this review, we have focused on cytological and transcriptional compartmentalization which is unique to the cerebellum in the staggerer mouse. The staggerer mouse carries a deletion in the gene encoding the nuclear hormone receptor RORα, which results in severe impairments of phenotypic differentiation of cerebellar Purkinje cells (PC). This is characterized by reduced cell number, ectopia, smaller cell size and rudimentary dendrites without tertiary dendritic spines. Purkinje cells with different cytological features were distributed in discrete mediolateral regions within the staggerer cerebellum. Overlapping with the cytological compartments, PC with different levels for calbindin and inositol 1,4,5‐trisphosphate receptor type 1 mRNA, which are homogeneously expressed in adult wild‐type mice, form distinct transcriptional compartments. Furthermore, some compartments are associated with additional expression of NMDA receptor channel subunit mRNA which are absent in wild‐type PC. Although the unique compartmentalization observed in the staggerer cerebellum emerges as the result of RORα gene mutation, there are no mediolateral differences in the RORα expression itself in the wild‐type PC at any developmental stage. Thus, the formation of cytological and transcriptional compartments in the staggerer mouse should be ascxibed to RORα‐independent, cellular/molecular mechanisms which operate unevenly along the mediolateral cerebellar axis. With the cooperation of RORα‐dependent and ‐independent mechanisms, the PC attains full cytodifferentiation during cerebellar development.

Intrinsic connections in the anterior dorsal ventricular ridge of the lizard psammodromus algirus

We have studied the intrinsic connections of the anterior dorsal ventricular ridge (ADVR) in the lacertid lizard Psammodromus algirus by means of retrograde transport of horseradish peroxidase (HRP) and fluorescent labeling with the lipophilic carbocyanine dye DiI. We injected HRP into different regions in the ADVR arrayed in a medial-to-lateral sequence, with each consisting of three distinct superficial-to-deep zones. When HRP was injected into a given region, many labeled neurons (always located ipsilateral to the injection site) were found at all mediolateral regions of ADVR in locations rostrally distant from the injection site. DiI crystals were applied on different superficial-to-deep zones within each region. Two patterns could be recognized: DiI crystals applied on the periventricular (most superficial) zone resulted in a labeling of cells widely distributed throughout the ADVR independently of the mediolateral region of the application site, whereas DiI crystals applied on deeper zones resulted in a staining of cells mostly restricted to a narrow radial area. Results from both types of labeling confirm that the ADVR has a prominent radial component in its intrinsic organization, but they also demonstrate that some areas of the ADVR receive projections from distant, rostrally located neurons in every ipsilateral region of the ridge itself, which establishes a clear non-radial component. This organization may have important functional properties with regard to a putative integration of different sensory modalities conveyed by thalamic afferent fibers to the ADVR. Last, we analyzed some evolutionary implications of our results. © 1996 Wiley-Liss, Inc.

Intrinsic connections in the anterior dorsal ventricular ridge of the lizard Psammodromus algirus.

We have studied the intrinsic connections of the anterior dorsal ventricular ridge (ADVR) in the lacertid lizard Psammodromus algirus by means of retrograde transport of horseradish peroxidase (HRP) and fluorescent labeling with the lipophilic carbocyanine dye DiI. We injected HRP into different regions in the ADVR arrayed in a medial-to-lateral sequence, with each consisting of three distinct superficial-to-deep zones. When HRP was injected into a given region, many labeled neurons (always located ipsilateral to the injection site) were found at all mediolateral regions of ADVR in locations rostrally distant from the injection site. DiI crystals were applied on different superficial-to-deep zones within each region. Two patterns could be recognized: DiI crystals applied on the periventricular (most superficial) zone resulted in a labeling of cells widely distributed throughout the ADVR independently of the mediolateral region of the application site, whereas DiI crystals applied on deeper zones resulted in a staining of cells mostly restricted to a narrow radial area. Results from both types of labeling confirm that the ADVR has a prominent radial component in its intrinsic organization, but they also demonstrate that some areas of the ADVR receive projections from distant, rostrally located neurons in every ipsilateral region of the ridge itself, which establishes a clear non-radial component. This organization may have important functional properties with regard to a putative integration of different sensory modalities conveyed by thalamic afferent fibers to the ADVR. Last, we analyzed some evolutionary implications of our results.

Evidence of early topographic organization in the embryonic olivocerebellar projection: A model system for the study of pattern formation processes in the central nervous system

Many projection systems within the peripheral and central nervous system are topographically organized, and it has become increasingly clear that interactions which occur during development determine the projection patterns these systems exhibit in the adult. The olivocerebellar system was chosen as a model system for this study of afferent pattern formation because it has several characteristics which lend themselves to a study of this type. Applications of horseradish peroxidase were made to both the cerebellar primordium and to the inferior olive of embryonic and neonatal mice using an in vitro perfusion system to support the tissue during the transport period. Fibers labeled after restricted olivary applications are limited to particular mediolateral regions of the cerebellum. Similarly, olivary cells retrogradely labeled after discrete cerebellar applications are restricted to particular olivary subdivisions. The results indicate that the olivocerebellar projection displays elements of topographic organization as early as E15 and that the pattern displayed is roughly comparable to that of the adult mammal. The observed trajectories of olivocerebellar fibers and their concomitant association with both Purkinje and cerebellar nuclear cells during embryonic development suggests a role for either or both cell types in the pattern formation process.

Sprouting of peripherally regenerating primary sensory neurones in the adult central nervous system

We have studied the ability of primary afferent neurones to proliferate within the grey matter of the dorsal horn following the degeneration of other, nearby, afferent fibres. The peripheral branches of primary afferents have the capacity to regenerate successfully over long distances, and we have examined the possibility that when they are so doing, the neurones' status changes to facilitate greatly the sprouting of afferent fibres within the dorsal horn. "Spared root" preparations (rhizotomies of L3, L4, L6, S1, and the caudal half of L5, sparing the rostral half of the L5 dorsal root) were made in adult rats. In some animals (acute preparations) the distribution of the central terminals of the spared root was assessed by labelling the sciatic nerve with WGA-HRP at the time of the rhizotomies. In other animals (chronic preparations), symmetrical bilateral spared roots were made and the sciatic nerve on one side was concomitantly crushed to trigger regrowth of the peripheral branches of these axons. Eight to 10 weeks later the sciatic nerves on both sides were labelled with HRP-WGA. In the acute preparations the reaction product was found in a limited rostrocaudal and mediolateral region of the dorsal horn. In lamina II (the lamina of densest labelling) the labelled terminals occupied an average of 1.17 +/- 0.21 mm2. In chronic preparations, the area of labelled terminals on the side of the uncrushed sciatic nerve was 1.34 +/- 0.28 mm2 (not significantly different from acute animals). However, the labelled area on the side of the crushed sciatic nerve was significantly greater, averaging 2.17 +/- 0.14 mm2.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of osteogenic and chondrogenic potentials along the mediolateral axis of the embryonic chick mandible

Various regions of the mandibular process were tested for these potentials to determine whether regional differences exist and vary with embryonic age. Mandibular processes from HH stages 17–21.5 were cultured and grafted intact, or were subdivided into medial, mediolateral and lateral fragments and the separate regions cultured or grafted. The intact mandible from all these stages can form cartilage and membrane bone, but the 3 regions are not equally osteogenic and chondrogenic. The lateral region from all stages could form cartilage and membrane bone; the mediolateral region could form cartilage and membrane bone but, in mediolateral fragments from HH stage 17, membrane bone was formed only in scant amounts. The medial region from HH stages 17 and 18 formed cartilage in only 50 per cent of cases and never formed membrane bone. By HH stage 20, the medial region could form membrane bone, but only in scant amounts. Medial fragments from HH stage 21.5 formed extensive membrane bone and cartilage. The acquisition of these potentials, therefore, proceeds in a lateral-to-medial sequence, and the acquisition of an osteogenic potential lags slightly behind that of a chondrogenic potential. These findings do not indicate the mechanisms by which the two subpopulations of chondrogenic and osteogenic cells are distinguished from one another, but they give the temporal and spatial sequence in which this determination must occur.

Thalamic projections to the paleostriatum and neostriatum in the pigeon ( Columba livia)

Thalamic projections to the paleostriatum and neostriatum in the pigeon have been studied using wheat germ agglutinin-horseradish peroxidase in anterograde and retrograde tracing experiments. Injections centred on different mediolateral regions of the dorsal thalamus produced terminal labelling in correspondingly different mediolateral regions of the striatal complex, comprising paleostriatum augmentation and lobus parolfactorius, within the ventral paleostriatum, 41 and within the neostriatum. Injections into various loci within these regions retrogradely labelled numerous neurons within the dorsal thalamus, the location of which varied systematically with the injection placement; and within various regions of the midbrain and pons.

The avian somatosensory system. I. Primary spinal afferent input to the spinal cord and brainstem in the pigeon (Columba livia).

The process of transganglionic transport was used to determine the pattern of primary afferent projections to the spinal cord and brainstem in the pigeon by (1) applying horseradish peroxidase (HRP) to various peripheral nerves in the leg or wing, (2) by injecting HRP-lectin into feather follicles of the wing or tail, and (3) by injecting HRP-lectin into various muscles of the leg or wing. In the spinal cord major peripheral nerves were represented heavily throughout the dorsal horn laminae but sparsely in more ventral laminae. The representations of these different nerves tended to be located in different mediolateral regions of the dorsal horn. Cutaneous nerves and feather follicles were represented predominantly in laminae I and II, and different sets of follicles were represented in different mediolateral regions of these laminae. Afferent labelling from muscles of the leg and wing was located in the lateral portion of the dorsal horn, predominantly in laminae I, II, and IV. In the caudal medulla the representation of the leg within the gracile nucleus was medial to and separate from that of the wing within the cuneate nucleus (Cu). The wing representation, however, extended laterally throughout the external cuneate nucleus (CuE) and lateral regions of the descending trigeminal tract. There was less evidence of separation of the limb representations at more rostral medullary levels where they both occupied predominantly CuE. Afferent labelling from cutaneous nerves and feather follicles was distributed lightly throughout Cu and CuE, and from muscles of both limbs primarily throughout CuE. There was also a small but specific projection from the limbs to the nucleus of the solitary tract, and from the wing to the principal sensory trigeminal nucleus. These results are discussed within a comparative context with a view to highlighting the similarities and differences in the pattern of primary afferent central projections in different vertebrates.

Synaptic organization of the cerebello-thalamo-cerebral pathway in the cat. II. Input-output organization of single thalamocortical neurons in the ventrolateral thalamus

Input-output neural organization of single thalamocortical (T-C) neurons in the ventrolateral nucleus (VL) of the thalamus was investigated using an intracellular recording technique in the anesthetized cat. Stimulation of the dentate (DN) and the interpositus (IN) nuclei produced monosynaptic unitary EPSPs of large amplitude in T-C neurons projecting to the motor cortex or area 6 over the entire mediolateral region of VL. The thalamic projections from DN and IN are very wide and there is a considerable overlap between the dentate and the interpositus projection areas in VL. And in this overlapping area, a considerable number of T-C neurons (50%) receive inputs from both DN and IN. More than 40% of T-C neurons were antidromically activated from widely separated electrodes in the motor cortex, indicating that the cortical arbolization of single T-C neurons is very wide and the number of these neurons with widely divergent projections is considerably large.

Somatotopically inappropriate projections of single hair follicle afferent fibres to the cat spinal cord.

In the L7 segment of cats anaesthetized with alpha-chloralose, single hair follicle afferent (h.f.a.) fibres were injected intra-axonally with horseradish peroxidase (HRP). In the same animal light tactile stimuli were used to plot the receptive fields of laminae III and IV dorsal horn neurons (d.h.n.s) at various rostrocaudal levels below the stained segment of axon. The results showed that eight of the ten injected axons gave rise to collaterals in somatotopically inappropriate regions of the dorsal horn, i.e. those regions in which the receptive fields of d.h.n.s did not encompass the receptive field of the stained h.f.a. Over-all the stained h.f.a.s gave rise to fifty-three collaterals, twenty-two (42%) of which projected to somatotopically inappropriate regions of the dorsal horn. Collateral arborizations in the somatotopically inappropriate region were always located in the same mediolateral region of the dorsal horn as those arborizations in the appropriate region. Collateral arborizations more than 600 microns from the somatotopically appropriate region had few branches and gave rise to very few boutons compared with those within the appropriate region.

The olivocerebellar projection to the uvula in the mouse.

The organization of the olivocerebellar projection in the mouse was studied with the use of microinjections of horseradish peroxidase (HRP) or HRP conjugated to wheat germ agglutinin (WGA-HRP). Injections were made in medial, intermediate, and lateral sites along the width of the uvula. The purpose of this investigation was to determine the subnuclear origin of olivary afferents to different mediolateral regions of the uvula. Injections made in or adjacent to the midline of the uvula resulted in the retrograde labeling of cells, bilaterally in the caudal portion of the medial accessory olive (MAO). These labeled cells were located primarily in subnucleus C and nucleus beta of the MAO. Injections into the intermediate part of the uvula resulted in the labeling of cells in the caudal MAO (primarily nucleus beta), the dorsomedial cell column (dmcc), and a few cells in the ventral lamella of the principal olive (vPO). Laterally placed injections produced labeling of cells in dmcc and the vPO. These results are discussed in reference to the parasagittal organization of olivary afferents to the cerebellar cortex in the mouse (Beyerl et al., '82) and the organization of afferents to the involved regions of the inferior olivary (IO) complex. It is suggested that these parasagittal zones in the uvula may play different roles in the control of eye movements.

The cercus-to-giant interneuron system in the bushcricketTettigonia cantans: Morphology and response to low-frequency sound

1. The response characteristics of the cercus-to-giant interneuron system in the bushcricketTettigonia cantans to low-frequency airborne sound have been studied using intracellular or quasi-intracellular recording; the morphology of the giant interneurons has been investigated using Lucifer Yellow filling and axonal backfill with cobalt. 2. The giant interneurons excited by the cereal sensory afferents can be classified into four types based on their time courses of firing (Fig. 1): ‘quasi’-tonic, tonic burst, phasic and ‘sustained’ burst type, respectively. 3. The giant interneurons in the bushcricket are maximally sensitive to air particle displacement at 300 Hz and the lowest threshold is less than 0.1 μm (Fig. 2). 4. The intensity characteristics for three tpyes of the giant interneurons (Type I, II and IV) indicate that spike counts for these interneurons increase with increasing stimulus amplitude (Fig. 3). The phasic type of the interneuron (Type III) fired more frequently only one spike to each sound stimulus. 5. The cercus-to-giant interneuron system in the bushcricket is composed of seven bilateral pairs of the interneurons, each of which possesses a cell body, neurite and dendrites within the last abdominal ganglion and also has a giant axon which ascends the ventral nerve cord. Compared with other neurons, the axons of these neurons are giant and have diameters of 8–15 μm for GI1 and GI4 to 7, and about 5 μm for GI2 and GI3. The position of the cell body and the locations and orientations of the major processes are characteristic for each giant interneuron (Fig. 5). 6. The projections of single cereal afferents are made visible with Lucifer Yellow filling, which restricted within the ipsilateral half of the terminal ganglion. There is a great degree of the overlap between the cereal projections and the dendritic fields of the GIs (Fig. 4). 7. The branching details of the investigated giant interneurons within the thoracic ganglia and the brain are disclosed by Lucifer Yellow filling (Figs. 6, 7). The neurons Type I and III send two main collaterals medially directed within the prothoracic ganglion and the neuron Type IV sends three collaterals close to the midline of this ganglion. Within the metathoracic ganglion the neuron Type II sends three medially directed collaterals. At the ends of many branching terminals the buttonlike enlargements with stronger fluorescence can be seen and probably these terminals are the presynaptic endings. The projections of the axons of the GIs also can be found within the brain. The axons run through the tritocerebrum and deutocerebrum and terminate mainly in the mediolateral region of the lateral posterior protocerebrum.

Representations of the body surface in postcentral parietal cortex of Macaca fascicularis.

The somatotopic organization of the postcentral parietal cortex of the Old World monkey, Macaca fascicularis, was determined with multi-unit microelectrode recordings. The results lead to the following conclusions: 1) There are at least two complete and systematic representations of the contralateral body surface in the cortex of the postcentral gyrus. One representation is contained within Area 3b, the other within Area 1. 2) While there are important differences in the organization of the two representations, they are basically mirror-images of each other. 3) Each representation maintains body-surface adjacency by cortical adjacency in some mediolateral regions. In other regions, two types of discontinuities can be described: first, in which adjacent body surfaces are represented in separate cortical loci; second, in which adjacent cortical regions represent disparate body-surface regions. The internal organization of each representation is better described as a composite of somatotopic regions (Merzenich et al., '78) than as a serial array of dermatomal bands, or as a "homunculus." 4) While architectonic Area 2 responds to stimulation of deep body tissue, at least parts of Area 2 also respond to cutaneous stimulation. The organiation of the cutaneous representation of the hand in Area 2 is basically a mirror-image of the hand representation in Area 1. 5) Area 3a is activated by deep body tissue stimulation, suggesting the possibility of a fourth body representation within the traditional "S-I" region of somatosensory cortex in macaques. In accord with a previous study in a New World monkey (Merzenich et al., '78), we suggest that the cutaneous representation in Area 3b be considered as SI proper, and that the cutaneous representation in Area 1 be termed the posterior cutaneous field. Furthermore, based on the orientation of the representations of the body surface, as well as other factors, we suggest that the representation in Area 3b is homologous to "SmI" (or "SI") in non-primates.