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Birth, migration, incorporation, and death of vocal control neurons in adult songbirds.

Neurogenesis continues in the brain of adult birds. These cells are born in the ventricular zone of the lateral ventricles. Young neurons then migrate long distances guided, in part, by radial cell processes and become incorporated throughout most of the telencephalon. In songbirds, the high vocal center (HVC), which is important for the production of learned song, receives many of its neurons after hatching. HVC neurons which project to the robust nucleus of the archistriatum to form part of the efferent pathway for song production, and HVC interneurons continue to be added throughout life. In contrast, Area X-projecting HVC cells, thought to be part of a circuit necessary for song learning but not essential for adult song production, are only born in the embryo. New neurons in HVC of juvenile and adult birds replace older cells that die. There is a correlation between seasonal cell turnover rates (addition and loss) and testosterone levels in adult male canaries. Available evidence suggests that steroid hormones control the recruitment and/or survival of new HVC neurons, but not their production. The functions of neuronal replacement in adult birds remain unclear. However, rates of HVC neuron turnover are highest at times of year when canaries modify their songs. Replaceable HVC neurons may participate in the modification of perceptual memories or motor programs for song production. In contrast, permanent HVC neurons could hold long-lasting song-related information. The unexpected large-scale production of neurons in the adult brain holds important clues about brain function and, in particular, about the neural control of a learned behavior--birdsong.

Animals↗

Different origins and developmental histories of transient neurons in the marginal zone of the fetal and neonatal rat cortex.

Two major classes of early-born neurons are distinguished during early corticogenesis in the rat. The first class is formed by the cortical pioneer neurons, which are born in the ventricular neuroepithelium all over the cortical primordium. They appear at embryonic day (E) 11.5 in the lateral aspect of the telencephalic vesicle and cover its whole surface on E12. These cells, which show intense immunoreactivity for calbindin and calretinin, are characterized by their large size and axonal projection. They remain in the marginal zone after the formation of the cortical plate; they project first into the ventricular zone, and then into the subplate and the internal capsule. Therefore, these cells are the origin of the earliest efferent pathway of the developing cortex. Pioneer neurons are only present in prenatal brains. The second class is formed by subpial granule neurons, which form the subpial granular layer (SGL), previously considered to be found exclusively in the human cortex. SGL neurons are smaller than pioneer neurons. They are generated in a transient compartment of the retrobulbar ventricle between E12 and E14, and we propose the hypothesis that they invade the marginal zone, through tangential subpial migration, at different moments of fetal life. SGL neurons contain calbindin, calretinin, and gamma-aminobutyric acid (GABA), but the GABA-immunoreactive group becomes inconspicuous before birth. The extracellular matrix-like glycoprotein reelin, a molecule crucial for cortical lamination, is prenatally expressed by SGL neurons; postnatally, it is present in both Cajal-Retzius cells and subpial pyriform cells, both derivatives of SGL cells. In the rat, Cajal-Retzius cells are horizontal neurons that remain only until the end of the first postnatal week. They are located in layer I at a critical distance of approximately 20 microm from the pial surface and express reelin and, only occasionally, calretinin. Subpial pyriform cells coexpress reelin and calretinin and remain in layer I longer than Cajal-Retzius cells. Both pioneer neurons and subpial granule neurons are specific to the cortex. They mark the limit between the rudimentary cerebral cortex and olfactory bulb in the rat during early corticogenesis.

Aging↗

[Activation of striatum cholinergic system improves attention to conditioned stimuli].

Activation and blockade of the dog striatal cholinergic system yielded data suggesting that the cholinergic system of the striatum takes part in regulation of attention to significant stimuli working through motor structures involved in indirect efferent pathways as well as through sensory systems, too. The two possible mechanisms of sensory regulation of the attention processes by the striatal cholinergic system have been outlined.

Acetylcholine↗

Organization of efferent extraspinal sympathetic pathways in Rana esculenta.

Origin and distribution of pre- and postsynaptic fibres in the sympathetic trunk of Rana esculenta (from ganglion 3 to ganglion 10) have been investigated by means of extracellular recordings. Two systems conducting efferent information appear to exist: 1) a system made of faster conducting fibres (B group pre- and postsynaptic fibres); presynaptic fibres originating from a very high monosegmental source (4th spinal root); postsynaptic fibres leave the sympathetic chain plurisegmentally (rami communicantes 5-10); 2) a system made of slower conducting fibres (C group pre- and postsynaptic fibres) originating plurisegmentally from spinal roots 5-8. Intracellular recordings have shown that: 1) integrative processes take place in the amphibian sympathetic trunk, as in the mammalian one, but are quantitatively lesser. Homonomous (B-B) and heteronomous (B-C) convergence has been observed in B neurons, and also the convergence of a collateral of a C postsynaptic axon on B neurons. 2) posthumous depolarizations are present: these are events modulating the activity of sympathetic neurons. In B neurons posthumous depolarization follows orthodromic responses, and a late posthumous depolarization can be seen in B and C neurons following either ortho- or antidromic stimulation.

Animals↗

Maturation of fastest afferent and efferent central and peripheral pathways: no evidence for a constancy of central conduction delays.

The maturation of the fastest afferent and efferent central and peripheral pathways was analysed using the recording of somatosensory evoked potentials of the median nerve stimulation for afferent conduction and magnetoelectrical stimulation of motor cortex to the thenar muscles for efferent conduction. Both afferent and efferent central pathways showed a prolonged maturational pattern with adult values being reached by the age of 5 to 7 years for the afferent and by the age of around 10 years for the efferent pathway. In contrast, the maturation for peripheral afferent and efferent pathways showed a similar trend with a fairly constant conduction velocity reached around the age of 3 years. There was no evidence for a constancy of central conduction delays in both afferent and efferent pathway which has been supposed as a possible mechanism for a temporal stability in feedback loops involved in motor learning processes during development. It is concluded that the prolonged maturational central conduction time precludes the usage of a fixed temporal timing pattern during development in the human sensory motor system.

Adolescent↗

Lymphocyte targeting of the central nervous system: a review of afferent and efferent CNS-immune pathways.

The central nervous system (CNS) in considered to be an immunological privileged site. However, inflammatory reactions in response to virus infections, in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE) suggest that there are definite connections between the CNS and the immune system. In this review, we examine evidence for afferent and efferent pathways of communication between the CNS and the immune system, the pivotal role of regional lymph nodes in T-cell mediated autoimmune disease of the CNS, and the factors involved in lymphocyte targeting of the CNS. Afferent pathways of lymphatic drainage of the brain are well established in a variety of species, especially rodents. Fluid and antigens appear to drain along perivascular spaces populated by immunocompetent perivascular cells. Drainage pathways connect directly via the cribriform plate to nasal lymphatics and cervical lymph nodes. Soluble antigens draining from the brain induce antibody production in the cervical lymph nodes. Using a model of cryolesion-enhanced EAE, we review the role of lymphatic drainage and cervical lymph nodes in the enhancement of cerebral EAE. If a brain wound in the form of a cryolesion is produced 8 days post inoculation (dpi) of antigen in the induction of acute EAE, there is a 6-fold increase in severity of cerebral EAE by 15 dpi. Removal of the cervical lymph nodes significantly reduces such enhancement of EAE. These findings suggest that drainage of antigens from the brain to the cervical lymph nodes, in the presence of activated lymphocytes in the meninges or CNS, results in an enhanced second wave of lymphocytes targeting the brain. In examining the efferent immune pathway by which lymphocytes home to the CNS, several studies have characterized the phenotype of infiltrating T lymphocytes by the use of immunocytochemistry or FACS analysis. T-cells infiltrating the CNS are recently activated/memory lymphocytes typified by their high expression of CD44, LFA-1 and ICAM-1 and low expression of CD45RB in the mouse. Following the induction of EAE in susceptible mice, ICAM-1 and VCAM-1 are dramatically upregulated on CNS vessels; lymphocytes bind to such vessels via the interaction of their known ligands, LFA-1/Mac-1 and alpha 4-integrins, at least in vitro. It appears that alpha 4-integrin plays a key role in lymphocyte recruitment across the blood-brain barrier and may be a major factor in lymphocyte targeting of the CNS. Definition of factors involved in the afferent and efferent connections between the CNS and the immune system may clarify mechanisms involved in immune privilege of the CNS and may open significant therapeutic opportunities for multiple sclerosis.

Afferent Pathways↗

Certain efferent cortical fiber pathways of the Mongolian gerbil (Meriones unguiculatus).

Three areas of responsive cortex were demonstrated by electrical stimulation in the gerbil. Low voltage stimulation of frontal areas yielded a sequential pattern of discrete contralateral movements. Proceeding from a rostroventral to a caudodorsal position facial movements were obtained followed by upper extremity, trunk and lower extremity movements. This area includes primary motor cortex (area 4) in the gerbil. A comparable rostrocaudal motor pattern was obtained by stimulation above the rhinal fissure (insular cortex) and also from certain parietal areas. Although the sequential motor pattern was obvious in these additional areas of excitable cortex, the movements were more generalized and slightly higher voltages were required to obtain satisfactory results. A series of destructive lesions were made in each of these cortial areas. Subsequent degeneration studies, using reduced silver techniques, revealed that frontal and parietal cortex gave rise to corticospinal fibers. In addition all three areas gave rise to fibers which coursed to certain extrapyramidal nuclei of the basal ganglia, ventral thalamus, midbrain tegmentum, and medullary reticular formation.

Animals↗

Role of the parasympathetic nervous system and of cholinergic mechanisms in bronchial hyperreactivity.

The parasympathetic nervous system of the respiratory tract is involved in the control of airway calibre in three ways: through afferent nerve pathways (pulmonary reflexes); through efferent nerve pathways (reflexes, interaction between efferent vagus and mediators or modulating transmitter substances) and through cholinergic muscarinic receptors and postreceptor mechanisms in the target organ. To what extent do these mechanisms contribute to airway hyperreactivity? Pulmonary reflexes: Reflex bronchoconstriction has been established in divided lung experiments for histamine and in experiments involving an isolated segment of trachea for SO2. A reflex pathway is the most likely explanation for the heightened reactivity induced by aerosols of prostaglandin E2 and by maximal respiratory manoeuvers. Reflex bronchoconstriction is mediated through rapidly adapting ("irritant") receptors and through C-fibre endings. The influence of C-fibre endings is greater than hitherto suspected and many effects ascribed to irritant receptors are probably due to stimulation of C-fibre endings which outnumber myelinated fibres 3-4 to 1. From studies on the control of respiration (which reflect more directly the state of sensory receptors in the airways than studies of airway calibre) it appears that the activity of C-fibre endings increases during ozone-induced hyperreactivity. This could explain the increased bronchial reactivity seen in this condition. Interaction: Aerosols of serotonin cause bronchoconstriction when the vagus nerve is intact but have little effect during vagal block. This is an effect neither on afferent receptors nor on the end organ, but on the efferent nerve pathway. Interaction effects of this type ("cholinergic facilitation") are frequent and may be more important quantitatively than reflex effects. From data on serotonin and by analogy to other systems it appears that preganglionic and ganglionic sites are important points of interaction. Parasympathetic ganglia are located in the airway wall. Several transmitter substances have been identified in airway ganglia and in autonomic nerves, sensory and motor. Thus there seem to be convergent inputs capable of modulating transmission through the ganglia. An altered balance of converging ganglionic inputs may cause hyperreactivity. Receptors in airway smooth muscle may not be a homogeneous population. Muscarinic receptors are being classified into subgroups and the existence of at least 3 subtypes: M-1, M-2 and M-3 has been postulated. Their distribution depends on the tissue studied. They differ in agonist affinity messenger systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Axons of early generated neurons in cingulate cortex pioneer the corpus callosum.

The internal capsule and corpus callosum are the two major efferent axonal pathways of the mammalian neocortex. Previous studies have shown that the first cortical axons to grow through the internal capsule, the pathway from cortex to its subcortical targets, are extended by subplate neurons, which are the earliest generated neurons in the neocortex. Here, we characterize the origin of the first axons to project through the other major efferent pathway of the cortex, the midline corpus callosum, which connects the two cortical hemispheres. Using anterograde Dil tracing, we show that cortical axons first cross the midline through the nascent corpus callosum at E17. Retrograde Dil labeling from medial cortex at E18 reveals that these axons originate from a discrete group of neurons in medial (presumptive cingulate) cortex. These early callosal cells have complex morphologies with highly branched dendrites and later appear to take on a pyramidal form characteristic of callosal neurons in deep layers of cingulate cortex. 3H-thymidine birthdating demonstrates that these cells are predominantly generated on E14, making them among the earliest generated neurons in this cortical region. Injections of retrograde tracers in one cortical hemisphere at late embryonic or early postnatal ages result in substantial numbers of neurons labeled in the ipsilateral subplate, but only a few neurons labeled in the contralateral subplate. Thus, subplate neurons do not pioneer or ever project in significant numbers through the corpus callosum. We conclude that the two major efferent pathways from cortex, the corpus callosum and the internal capsule, are pioneered by developmentally and spatially distinct populations of early generated cortical neurons.

Aging↗

Functioning of olivocochlear bundle and speech perception in noise.

OBJECTIVES: To evaluate the effect of contralateral acoustic stimuli on speech identification scores and to correlate this effect to contralateral suppression of evoked otoacoustic emission. DESIGN: Ten normal-hearing children with good academic performance participated in the study. Speech identification scores were measured in quiet and with different ipsilateral signal to noise ratios in two conditions, with and without contralateral acoustic stimuli. Transient evoked otoacoustic emissions were recorded for 70 dB SPL clicks with and without contralateral acoustic stimuli. RESULTS: Findings revealed that contralateral acoustic stimuli enhanced speech perception when ipsilateral signal to noise ratios was +10 dB and +15 dB. This enhancement had significant positive correlation with contralateral suppression of OAE. CONCLUSIONS: The results of the present study support the hypothesis that medial olivocochlear bundle might aid in speech perception in noise, thereby suggesting a possible role of cochlear efferent fibers in hearing. The psychoacoustic measures can be used to evaluate the efferent auditory pathways, where it is not possible to record otoacoustic emissions.

Auditory Pathways↗

Mechanically evoked cerebral potentials and long-latency muscle responses in the evaluation of afferent and efferent long-loop pathways in humans.

Standing humans were subjected to sudden tilts of a platform toe-up. This resulted in a long-latency response in the anterior tibial muscle with a mean latency of 132 ms. The same physiological stimulus was applied to evoke cerebral potentials. The mechanically evoked potential was characterized by a positive peak with a mean latency of 76.4 ms. Absolute peak latencies were variable between subjects but the side difference after separate stimulation of both legs was only around 2 ms. The recording of both, mechanically evoked long-latency muscle responses and cerebral potentials allows a separate evaluation to be made of afferent and efferent central pathways.

Adult↗

Fastigial nucleus projections to the brain stem in beagles: pathways for autonomic regulation.

Efferent connections from a portion of the cerebellar fastigial nucleus were investigated using autoradiography. Bipolar stimulating electrodes were placed in the fastigial nucleus of anesthetized beagles and the area that produced increases in blood pressure and heart rate was localized. A mixture of [3H]leucine and [3H]proline (4:1) was injected into the area and autoradiograms of transported material were prepared. Injections filled the rostral and various parts of the caudal fastigial nucleus. Labeled axons reached the brain stem via two routes, the ipsilateral juxtarestiform body and the contralateral uncinate fasciculus. Ventral portions of the lateral vestibular nucleus were labeled bilaterally, projections to the inferior vestibular and medial vestibular nuclei are contralateral. Nucleus tractus solitarius was heavily labeled on the side opposite the injection. The contralateral medial reticular formation contained many labeled terminals and axons. Label was found in the nucleus reticularis ventralis, lateral reticular nucleus, nucleus gigantocellularis, nucleus pontis caudalis and the paramedian reticular nucleus. No terminal labeling was found in nucleus parvocellularis or nucleus ambiguous. Stimulation of the rostral fastigial nucleus produces increases in blood pressure and heart rate by generalized sympathoexcitation. Many cell groups which facilitate the activity of preganglionic sympathetic neurons do not receive direct fastigial input. It is suggested that that sympathoexcitation resulting from stimulation of the fastigial nucleus occurs through multisynaptic connections in the brain stem.

Animals↗

Peripheral organization of the vestibular efferent system in the frog: an electrophysiological study.

The distribution and the properties of efferent fibers in vestibular nerve were studied in the isolated frog labyrinth. Electrical stimulation of the central stump of any vestibular nerve branchlet elicited compound action potentials in all the other eighth nerve branchlets, indicating the existence of neural links between the various vestibular organs. The same experimental paradigm, when repeated in frogs with chronic section of the eighth nerve roots, demonstrated that these pathways are efferent collaterals extending to all vestibular organs. There are more collaterals linking the 3 semicircular canals than the otolith organs and the otoliths with the canal organs. Efferent connections in the eighth nerve were preserved in full after ablation of the ipsilateral hemi-cerebellum, suggesting that the efferent pathways probably originate in the brainstem. Intracellular recordings from single afferent fibers of both canal and otolith organs revealed that efferent fiber activation could elicit either inhibition or facilitation of the receptor discharge. It was concluded that the frog efferent vestibular system is endowed with non-selective control channels which allow single neurons to influence the receptor activity of different labyrinthine organs.

Animals↗

The effect of vestibular nerve section upon tinnitus.

This paper reviews the published evidence regarding the effect of vestibular nerve section upon tinnitus. This is of relevance not only for those performing and undergoing this procedure, but also for those considering the hypothesis that auditory efferent system dysfunction may be influential in tinnitus perception. The auditory medial efferent fibres within the internal auditory canal run within the inferior vestibular nerve, only joining the cochlear nerve at the anastomosis of Oort, a bundle of 1300 fibres running from the saccular branch of the inferior vestibular nerve to the cochlear nerve. Vestibular nerve section procedures therefore section this efferent olivocochlear pathway, and ablate efferent influence upon that cochlear. If auditory efferent dysfunction is involved in tinnitus perception, this ablation might influence the tinnitus status of that patient. A literature search identified 18 papers mentioning tinnitus status after vestibular nerve section, describing the experiences of a total of 1318 patients. The proportion of patients in whom tinnitus was said to be exacerbated postoperatively ranged from 0% to 60%, with a mean of 16.4% (standard deviation 14.0). The proportion of patients in whom tinnitus was unchanged was 17% to 72% (mean 38.5%, standard deviation 15.6), and in whom tinnitus was said to be improved was 6% to 61% (mean 37.2%, standard deviation 15.2). In the majority of patients undergoing this procedure, ablation of auditory efferent input (and thus total efferent dysfunction) to the cochlea was not associated with an exacerbation of tinnitus. The finding of this review is that efferent dysfunction after vestibular nerve section does not consistently worsen tinnitus.

Humans↗

The efferent cardiac lymphatic pathways in the macaque monkey.

In ten postmortem hearts of the Macaque monkey (M. mulatta), the coronary lymphatics were visualized using an India ink suspension in 2% gelatin. The left coronary lymphatic initially passed to the dorsal surface of the aortic arch. In five hearts, this lymphatic went directly to the cardiac lymph node, whereas in the others, it first ascended to the left superior tracheobronchial node and then interconnected with the cardiac lymph node. The right coronary lymphatic usually passed in front of the ascending aorta and common arterial (brachiocephalic) trunk and entered the cardiac lymph node. In two hearts, however, the right coronary lymphatic first ascended to an anterior transverse mediastinal node and from here lymphatics joined the cardiac lymph node. Those lymphatics that passed cephalad from the cardiac lymph node to the right anterior mediastinal nodes and the right paratracheal nodes ultimately emptied into the right venous angle. Those lymphatics that passed cephalad from the cardiac lymph node to the anterior transverse mediastinal nodes ultimately emptied into the left venous angle. In five other Macaque monkeys (M. mulatta and M. fascicularis) after marker injection (T1824 blue dye and micropulverized barium sulfate) into the living heart or pericardium, lymphatic drainage beyond the base of the heart could not be demonstrated. Whereas postmortem morphologic studies suggest that the monkey coronary lymphatic system is amenable to obstruction by removal of the cardiac lymph node and interruption of its adjacent lymphatic connections, effective methods for visualizing the mediastinal lymphatic collecting system in the living monkey must be developed before experimental cardiac lymphatic ablation can be accomplished in this species.

Animals↗

Autonomic pathways regulating pancreatic exocrine secretion.

The parasympathetic (PNS) and sympathetic (SNS) and nervous systems densely innervate the exocrine pancreas. Efferent PNS pathways, consisting of central dorsal motor nucleus of the vagus (DMV) and peripheral pancreatic neurons, stimulate exocrine secretion. The DMV integrates cortical (olfactory, gustatory) and gastric, and intestinal vagal afferent input to determine central PNS outflow during cephalic, gastric and intestinal phases of exocrine secretion. Pancreatic neurons integrate DMV input with peripheral enteric, sympathetic, and, possibly, afferent axon reflexes to determine final PNS input to all exocrine effectors. Gut and islet hormones appear to modulate both central and peripheral PNS pathways. Preganglionic sympathetic neurons in the intermediolateral (IML) column of the spinal cord receive inputs from brain centers, some shared with the PNS, and innervate postganglionic neurons, mainly in prevertebral ganglia. Sympathetic innervation of the exocrine pancreas is primarily indirect, and inhibits secretion by decreasing blood flow and inhibiting transmission in pancreatic ganglia. Interactions between SNS and PNS pathways appear to occur in brain, spinal cord, pancreatic and prevertebral ganglia, and at neuroeffector synapses. Thus, the PNS and SNS pathways regulating the exocrine pancreas are directly or indirectly antagonistic at multiple sites: the state of exocrine secretion reflects the balance of these influences. Despite over a century of study, much remains to be understood about the connections of specific neurons forming pancreatic pathways, their processes of neurotransmission, and how disruption of these pathways contributes to pancreatic disease.

Animals↗

Neural components of distension-evoked secretory responses in the guinea-pig distal colon.

1. Using a Ussing chamber and neuronal retrograde tracing with 1,1'-didodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) we characterized the afferent and efferent neuronal pathways which mediated distension-evoked secretion in the guinea-pig distal colon. 2. Acute capsaicin application (10 microM) to the serosal site of the Ussing chamber evoked a secretory response which was blocked by tetrodotoxin (1 microM), the combined application of the NK1 and NK3 receptor antagonists CP-99,994-1 and SR 142801 (1 microM), and by combined application of atropine (10 microM) and the VIP receptor antagonist VIP(6-28) (10 microM). Functional desensitization of extrinsic primary afferents by long-term application of capsaicin significantly diminished distension-evoked secretion by 46 %. 3. After functional desensitization by capsaicin, serosal application of gadolinium (100 microM) inhibited the distension-evoked chloride secretion by 54 %; the L-type Ca(2+) channel blocker nifedipine (1 microM) and the 5-HT(1P) receptor antagonist renzapride (1 microM) had no effect. The combination of atropine and VIP(6-28) or the combination of NK1 and NK3 receptor antagonists almost abolished distension-evoked secretion. 4. The secretory response evoked by electrical field stimulation, carbachol (1 microM) or VIP (1 microM) was not attenuated by gadolinium. Field stimulation-evoked chloride secretion was not affected by blockade of NK1 and NK3 receptors. 5. Twelve per cent of DiI-labelled submucosal neurones with projections to the mucosa were immunoreactive for choline acetyltransferase, substance P and calbindin and very probably represented intrinsic primary afferent neurones. 6. Distension-evoked chloride secretion was mediated by capsaicin-sensitive extrinsic primary afferents and by stretch-sensitive intrinsic primary afferent neurones. Both the extrinsic and intrinsic afferents converge on common efferent pathways. These pathways consist of VIPergic and cholinergic secretomotor neurones that are activated via NK1 and NK3 receptors.

Afferent Pathways↗