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The percentage of projection neurons and local circuit neurons in different nuclei of the human thalamus.

A characteristic lipofuscin pigmentation permits reliable distinction of the various neuronal types forming thalamic nuclei of the human adult. Type I projection cells with coarse and vacuolated lipofuscin granules are distinguished from type II local circuit neurons with fine and intensely stained pigment and type III neurons devoid of pigment. There is by no means a uniform ratio of projection neurons versus local circuit neurons. A high proportion of local circuit neurons is found in nuclei of the anterior complex, a medium proportion in the specific nuclei of the lateral complex, and a low proportion in the reticular nucleus. The technique and the data provided are being used as a basis for investigations of the diseased human brain.

Cell Count

Cogeneration of retrogradely labeled corticocortical projection and GABA-immunoreactive local circuit neurons in cerebral cortex.

The times of origin of cortico-cortical projection neurons and local circuit neurons in rat visual cortex were determined. The birthdates of the projection neurons were assessed using a technique that combined retrograde labeling with lectin-bound horseradish peroxidase and tritiated thymidine autoradiography. The birthdates of some cortical local circuit neurons were determined by combining GABA immunocytochemistry with [3H]thymidine autoradiography. Double-labeled neurons (those with retrograde or immunoreactive label in their perikarya and autoradiographic silver grains over their nuclei) were born during the third week of gestation. Projection and local circuit neurons born on gestational day 14, 15, 17, 19 or 20 were located primarily in layer VIb, VIa, V, III or II, respectively. Thus, both populations of neurons are generated by parallel and concurrent inside-to-outside patterns.

Animals

The formation of new neuronal circuit between transplanted nigral dopamine neurons and non-immunoreactive axon terminals in the host rat caudate nucleus.

Using immunoelectron microscopic techniques, whether or not host neuronal elements newly form synaptic contact with the grafted dopamine (DA) neurons in the caudate nucleus of the rat with unilateral lesion in the nigrostriatal DA pathway was examined. Tyrosine hydroxylase (TH) was used as a marker for DA-containing structures. Motor imbalances after the lesion and before or after the transplantation were assessed by the amount of circlings after the injection of Met-amphetamine. In animals which recovered well from motor imbalance, non-immunoreactive axon terminals made synaptic contact with grafted TH-positive cell bodies and their dendrites. Since the incidence of these synapses was quite low in poorly recovered animals, the formation of a new neuronal circuit may be one of the important bases for behavior recovery.

Animals

Local circuit neurons of macaque monkey striate cortex: II. Neurons of laminae 5B and 6.

This study investigates the intrinsic organization of axons and dendrites of aspinous, local circuit neurons of the macaque monkey visual striate cortex. These investigations use Golgi Rapid preparations of cortical tissue from monkey aged 3 weeks postnatal to adult. We have earlier (Lund, '87) described local circuit neurons found within laminae 5A and 4C; this present account is of neurons found in the infragranular laminae 5B and 6. Since the majority of such neurons are GABAergic and therefore believed to be inhibitory, their role in laminae 5B and 6, the principal sources of efferent projections to subcortical regions, is of considerable importance. We find laminae 5B and 6 to have in common at least one general class of local circuit neuron-the "basket" neuron. However, a major difference is seen in the axonal projections to the superficial layers made by these and other local circuit neurons in the two laminae; lamina 5B has local circuit neurons with principal rising axon projections to lamina 2/3A, areas whereas lamina 6 has local circuit neurons with principal rising axon projections to divisions of 4C, 4A, and 3B. These local circuit neuron axon projections mimic the different patterns of apical dendritic and recurrent axon projections of pyramidal neurons lying within laminae 5B and 6, which are linked together by both dendritic and axonal arbors of local circuit neurons in their neuropils extending between the two laminae. The border zone between 5B and 6 is a specialized region with its own variety of horizontally oriented local circuit neurons, and it also serves as a special focus for pericellular axon arrays from a particular variety of local circuit neuron lying within lamina 6. These pericellular axon "baskets" surround the somata and initial dendritic segments of the largest pyramidal neurons of layer 6, which are known to project both to cortical area MT (V5) and to the superior colliculus (Fries et al., '85). Many of the local circuit neurons of layer 5B send axon trunks into the white matter, and we therefore, suspect them of providing efferent projections. The axons of lamina 6 local circuit neurons have not been found to make such clear-cut contributions to the white matter.

Animals

Local circuit neurons of macaque monkey striate cortex: III. Neurons of laminae 4B, 4A, and 3B.

We continue an investigation of the organization of local circuit neurons (largely inhibitory, GABAergic neurons, with smooth or sparsely spined dendrites) in the primary visual cortex of macaque monkey (Lund, '87: J. Comp. Neurol. 257:60-92; Lund et al., '88: J. Comp. Neurol. 276:1-29). This account covers local circuit neurons of layers 4B, 4A, and 3B; these three layers each receive different intrinsic second-order relays of principal thalamic inputs as well as receiving primary thalamic inputs in the case of two of the three laminae (4A and 3B). The study shows the existence of a number of different local circuit neurons making interlaminar projections between 4B, 4A, and 3B; each provides specific cross links between different combinations of the three laminae. It is known that the functional properties recorded physiologically from layers 4B, 4A, and 3B differ from one another and so these anatomical cross links may allow for correlation between different attributes of visual stimuli, e.g., color or motion, while still enabling separate processing of these different attributes to proceed in each of the three layers and be passed on to extrastriate areas. Whereas no spine-bearing neurons of layers 4B, 4A, or 3B provide "feedback" circuits to layer 4C (the source of their major intrinsic excitatory afferents), some of the local circuit neurons provide precisely structured axon feedback projections to divisions of 4C. The local circuit neurons also project to either lamina 5 or lamina 6, but not both and to superficial layers 3A, 2, and 1. Some local circuit neuron axon projections are of a dimension that would be confined to single functional clusters, e.g., cytochrome-rich "blobs," others reach out far enough to contact nearest neighbor "unlike" functional clusters, and yet others spread far enough to link repeating clusters of single function.

Aging

Maturation of rat visual cortex. III. Postnatal morphogenesis and synaptogenesis of local circuit neurons.

The postnatal development of 3 types of local circuit neurons in rat visual cortex was examined in Golgi and electron microscopic preparations. During the first postnatal week, smooth and sparsely spinous stellate, bitufted and bipolar neurons were identified in Golgi material by their characteristic dendritic arborizations. Morphological differentiation begins during this week, as each neuron sprouts dendrites which extend, branch and produce spines, and ends by day 21. This differentiation was traced by quantifying the somatic area and number of primary dendrites on stellate, bitufted and bipolar neurons in layer II/III or layer V. Neurons in deep cortex differentiate earlier than those in superficial laminae. On day 3, axons are evident as short, straight processes, however, by day 6, many axons have branches and varicosities. The increase in the complexity of the axonal trees continues during the second and third postnatal weeks. Since the axons of stellate and bitufted neurons form synapses with the somata of pyramidal neurons, an index of the synaptogenesis of these neurons was traced by counting the numbers of synapses on the somata of pyramidal neurons. The mean number of axosomatic synapses increases steadily from day 3 to day 30. Layer V pyramidal neurons form axosomatic synapses before pyramidal neurons in layer II/III. In conclusion, the morphology of local circuit neurons develops during the period after they migrate into cortex. The principle that cortical local circuit neurons develop after projection neurons only applies for the synaptogenesis of the axon, but not for the maturation of the cell body and dendrites.

Aging

Local circuit neurons of macaque monkey striate cortex: I. Neurons of laminae 4C and 5A.

A study has been made, using Golgi preparations, of the organization of neurons with smooth or sparsely spined dendrites, here called local circuit neurons, of the macaque monkey primary visual cortex. Since these neurons include those responsible for inhibitory circuitry of the cortex, a better understanding of their anatomical organization is essential to concepts of functional organization of the region. This account describes those neurons found with cell body and major dendritic spread within the thalamic recipient zone of lamina 4C and its border zone with lamina 5A. The neurons are grouped firstly in terms of in which laminar division the soma occurred--4C beta, 4C alpha or the border zone of 5A-4C beta--and secondly, into varieties on the basis of the interlaminar projection patterns of their axons. Most, if not all, of the local circuit neurons of these divisions have interlaminar axon projections as well as an arbor local to their cell body and dendritic field. These interlaminar projections are highly specific, targeting from one to five laminar divisions depending on the variety of neuron; on this basis 17 varieties of local circuit neuron are described. While the number of varieties appears dauntingly large in terms of understanding the functional circuitry of the region, the clear-cut organization of the interlaminar links may provide clues as to the information processing that concerns each neuron. The local circuit neuron axon projections can be related to a wealth of information already available concerning the laminar organization of afferent axons and efferent cell groups, the organization of spiny neuron intrinsic relays (presumed to be excitatory), and physiological properties of different laminar divisions. It is hoped that the information derived from this study can serve as a guide for correlated physiological-anatomical studies on single cells of the region.

Animals

Local circuit neurons of developing and mature macaque prefrontal cortex: Golgi and immunocytochemical characteristics.

A study has been made of the nonpyramidal, local circuit neurons in developing and mature macaque monkey prefrontal cortex with Golgi and immunocytochemical techniques. The area chosen for study is located between the cingulate gyrus and the ventral bank of the principal sulcus, and contains areas 9 and 46 as described by Walker (J. Comp. Neurol. 73:59-86, '40). In Golgi studies, the unique axonal features of impregnated neurons made possible the identification of thirteen separate classes of local circuit neurons. Five of these cell types, in their general characteristics, resembled classes identified in human prefrontal cortex, as well as in other cortical areas of macaque monkeys and other species. Measurements of the scale of axon arbors and dendritic fields of the Golgi-stained local circuit neurons also suggested particular spatial relationships of certain classes to the scale of intrinsic lattice connections made by the axons of pyramidal neurons in the same region. Similarities in morphology between cells described in human prefrontal cortex and neuron varieties described in this study indicate that this region of monkey prefrontal cortex may serve as a useful model for neuron populations in human prefrontal cortex. Sufficient morphological detail was present in immunocytochemical studies to suggest one or more identifying biochemical characteristics for seven of the thirteen classes of local circuit neurons. The calcium binding proteins, parvalbumin, calbindin D-28K, and calretinin, were found in chandelier and wide arbor neurons, neurogliaform cells, and double bouquet neurons, respectively. In addition, cholecystokinin immunoreactivity was present in medium arbor neurons and in narrow arbor cells connecting layers 2 and 4. Somatostatin 28(1-12) immunoreactivity was detected in beaded axon neurons in layers 5 and 6. This biochemical characterization of local circuit neurons, although incomplete, confirms the separate identity of at least some of the varieties distinguished by Golgi morphology, and allows a start to be made on studies examining changes in their functional state. The general inhibitory nature of these interneurons suggests that they are likely to play a crucial role in determining patterns of neural activation in the prefrontal cortex.

Animals

Relationship of the time of origin and death of neurons in rat somatosensory cortex: barrel versus septal cortex and projection versus local circuit neurons.

The birth of a neuron initiates a series of ontogenetic events, e.g., neuronal migration and differentiation. The outcomes of these events are neurons that successfully integrate into the cortical circuitry and neurons that are unsuccessful and ultimately die. The present study determined whether there is a relationship between the generation and death of cortical neurons. The decrease in the density of postmigratory neurons (heavily labeled by a single injection of [3H]thymidine) during normal development was used as an index of neuronal death. The survival indices of neurons varied with their times of origin. Neurons born from gestational day (G) 15 to G18 had the highest rates of survival. In contrast, the earliest and latest generated neurons (i.e., those born on G12-G13 and those born on G19-G21, respectively) had the lowest survival rates. The role of neuronal death in the formation of cortical patterns was determined by assessing the survival of neurons in the barrels and septa of somatosensory cortex. No differences in the survival index were determined for neurons in the C-row barrels and adjacent septa with a particular time of origin. The survival rate of projection and local circuit neurons was determined with a double-labeling technique. One label, [3H]thymidine, was used to determine the time of origin of the neurons. The second label was used to identify the chemical or hodological characteristics of a neuron; projection neurons were labeled either by retrograde transport of horseradish peroxidase or by glutamate immunohistochemistry, and local circuit neurons were immunohistochemically identified with an antibody directed against gamma-aminobutyric acid (GABA) antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Local circuit neurons in both the dentate gyrus and Ammon's horn establish synaptic connections with principal neurons in five day old rats: a morphological basis for inhibition in early development.

Glutamate decarboxylase (GAD)-positive and Golgi impregnated local circuit neurons of the hippocampal formation of five day old rats were examined in light and electron microscopic preparations. The ultrastructural features of these neurons were similar in both the dentate gyrus and CA1 area of Ammon's horn. Somata displayed a perikaryal cytoplasm rich in organelles but lacked organized Nissl bodies. Most nuclei showed intranuclear infoldings of varying degrees but no intranuclear sheets or rods were found. Somata and dendrites were contacted by relatively immature axon terminals that formed mainly symmetric synapses. The axons of local circuit neurons in both the dentate gyrus and Ammon's horn formed symmetric synapses with somata and dendrites of the principal neurons in these regions. Thus, both GAD-positive and Golgi-impregnated terminals of local circuit neurons were observed to form synapses with pyramidal and granule cells. These terminals were usually small and contained relatively few pleomorphic synaptic vesicles. The results show that a circuitry for inhibition is established in the 5 day old dentate gyrus and Ammon's horn, even though the local circuit neurons lack some of the typical adult ultrastructural features at this age.

Animals

Neuronal circuit mediating escape responses in crayfish.

The neuronal circuit underlying rapid abdominal flexion in response to phasic tactile stimulation comprises identified afferents, interneurons of two orders, a decision unit, and several motor neurons. The circuit is organized hierarchically as a " cascade" in which electrical synapses predominate at higher levels. Behavioral habituation results from lability at chemical junctions early in the pathway.

Abdomen

Positron emission tomography and magnetic resonance imaging: a review and a local circuit neurons hypo(dys)function hypothesis of schizophrenia.

A review of brain imaging (PET and MRI) studies on schizophrenia and recent data from neuroanatomy, neurophysiology, neuropathology, neurochemistry, neuropsychology, and cortical organization theory is integrated with the concept of local circuit neurons (LCNs) in a new hypothesis--the local circuit neurons hypo(dys)function hypothesis of schizophrenia--that attempts to explain the pathogenesis and pathophysiology of schizophrenia through a hypofunction (or dysfunction) of the local circuit neurons in prefrontal and limbic-temporal areas. This hypofunction (dysfunction) is then related to the neurocircuitry, neuropsychology, and psychopathology of schizophrenia.

Brain

Reaction time, impulse speed, overall synaptic delay and number of synapses in tactile reaction neuronal circuits of normal subjects and thinner sniffers.

In control subjects, warned auditory reaction time (RT) for a given effector organ was less than the warned visual RT for the same organ. The RT of the circuits between eye or ear or sites of tactile stimulation (SOS) and the index fingers were significantly shorter than that between eye or ear or the same SOS and the right or left big toes. The greater the distance between the SOS and the brain the longer the RT of the response by a given effector organ. The overall signal speed (OASS) from the neck to the index finger was less than that from the neck to the big toe. The OASS from the neck to a given effector was less than that from the toe to the same effector. Sensory nerve impulse speed was slightly faster than motor nerve impulse speed. The overall synaptic delay and estimated number of synapses (ENOS) of simple tactile reaction neuronal circuits of normal subjects did not significantly vary with site of tactile stimulation or effector organ. The mean number of synapses of various tactile reaction neuronal circuits of normal subjects was estimated to be between 69 and 77, which is far greater than the number of synapses in the touch-tactile and motor pathways combined. The overall synaptic delay in the tactile reaction neuronal circuits between SOS and the left and right big toes were significantly lower in sniffers than in control subjects. This may be due to a decrease in either the average synaptic delay, the number of synapses, or both in the tactile reaction neuronal circuits between sites of stimulation and big toes (but not index fingers) in sniffers.

Adolescent

Morphological studies of local circuit neurons in the cerebellar dentate nucleus of man.

Golgi preparations reveal the existence of two classes of nerve cells in the human dentate nucleus. Relatively large principal cells predominate. Small local circuit neurons are scattered throughout the nuclear gray. By means of a newly developed de-impregnation technique the pattern of pigmentation of both cell types can be studied. The principal cells show a considerable amount of finely granulated and faintly tinged pigment, whereas the local circuit neurons contain only a few large and intensely stained lipofuscin granules. The local circuit neurons give off a few smoothly contoured and rather extended dendrites. The axon is generated from either the cell body or a dendrite by way of a cone-shaped initial portion. A thin thread-like segment follows. Further distally, the caliber of the axon increases abruptly. This thick portion branches off several times at short intervals giving off fine processes with bead-like enlargements. Occasionally, a second axon is generated from these cells.

Cerebellum

Peripheral inflammation is associated with increased dynorphin immunoreactivity in both projection and local circuit neurons in the superficial dorsal horn of the rat lumbar spinal cord.

The present study combined the retrograde transport of fluorescent tracers with the immunocytochemical identification of dynorphin A(1-8) in superficial dorsal horn neurons to examine whether peripheral inflammation-induced dynorphin increases are found in local circuit neurons only or also in neurons projecting at least to the caudal mesencephalon. Evidence is presented that complete Freund's adjuvant-induced inflammation produces a large increase in the number of lamina I dynorphin-containing projection and non-projection neurons, and in the number of lamina II dynorphin local circuit neurons.

Animals

Synaptic connectivity of a local circuit neurone in lateral geniculate nucleus of the cat.

Although receptive fields of relay cells in the lateral geniculate nucleus of the cat nearly match those of their retinal afferents, only 10-20% of the synapses on these cells derive from the retina and are excitatory. Many more (30-40%) are inhibitory and largely control the gating of retinogeniculate transmission. These inhibitory synapses derive chiefly from two cell types: intrinsic local circuit neurones and cells in the adjacent perigeniculate nucleus. It has been difficult to study the functional organization of these inhibitory pathways; most efforts have relied on indirect approaches. Here we describe the use of direct techniques to study a local circuit neurone by iontophoresing horseradish peroxidase (HRP) into it, which completely labels the soma and processes of cells for subsequent light- and electron microscopic analysis. Although the response properties of the labelled cell are virtually indistinguishable from those of many relay cells, its morphology is typical of 'class 3' neurones (see Fig. 1 legend), which are widely believed to be interneurones (but see ref. 12). Here, we refer to the cell as a 'local circuit neurone', which allows for the possibility of a projection axon, rather than as an 'interneurone', a term that commonly excludes a projection axon. We find that the labelled cell has a myelinated axon, but that the axon loses its myelin within 50 microns of the soma and has not yet been traced further. The dendrites of the labelled cell possess presynaptic terminals that act as intrinsic sources of inhibition on geniculate relay cells. We also characterize other morphological aspects of this inhibitory circuitry.

Animals

Morphological and developmental characterization of local-circuit neurons in lamina III of the rat spinal cord.

Using the Golgi silver impregnation technique the present study examines the morphology and development of presumptive local circuit neurons in lamina III of the rat lumbar spinal cord. These neurons generate local axonal plexuses which remain within the gray matter and dendritic trees which arborize in lamina III and the inner zone of lamina II. Analysis of developmental stages supports the contention that these neurons have local axons which do not enter the white matter. These cells undergo axonal and dendritic maturation during the postnatal period, well after the maturation of long axon neurons. This pattern parallels the development of local circuit neurons in lamina II.

Animals

A prosencephalic neuronal circuit possibly involved in modulation of pain.

Both anatomical and physiological studies in cats substantiated the existence of a thalamus-cortex-thalamus neuronal circuit in which neurons in the centre median send fibers to wide areas of the cerebral cortex and the cerebral cortex, the motor cortex in particular, may send the fibers back to the parafascicular nucleus. The cortical neurons concerned tend to discharge spontaneously and constantly. These spontaneous discharges can be readily inhibited by the corticopetal impulses from the centre median, which itself can be activated by general afferent impulses. On the basis of this observation it is assumed that constantly discharging corticothalamic neurons may exert a tonic excitatory influence on the pain-receiving center, parafascicular nucleus, so as to keep it in a state of constant alertness to the tissue-damaging danger signals and that the inhibitory action of the ascending fibers from centre median would serve to suspend the excitatory action of the cortex on the parafascicular nucleus, resulting in relief of pain. The corticofugal fibers in this forebrain circuit terminating in the centromedian nucleus may reinforce the inhibitory action of the centromedian neurons so as to inhibit the spontaneous discharges of the cortical neurons . A self-regulating mechanism is thus formed by which a stabilized state of brain excitability can be maintained.

Animals