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PubMed1989

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↗
PubMed1971

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↗
PubMed1991

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↗
PubMed1996

Local circuit neurons in the medial prefrontal cortex (areas 24a,b,c, 25 and 32) in the monkey: I. Cell morphology and morphometrics.

This paper provides a comprehensive morphological description of local circuit neurons in the medial prefrontal cortex (mPFC: areas 24a, 24b, 24c, 25 and 32) of the monkey. Cortical interneurons were identified immunocytochemically by the expression of the calcium binding proteins calretinin (CR), parvalbumin (PV) and calbindin D-28k (CB). Interneurons were also identified using GABA immunocytochemistry. The areal and laminar distributions of CR, PV, and CB cells were consistent across mPFC; their morphological characteristics identified them as local circuit neurons. Throughout layers 2-6: CR immunoreactivity labelled double bouquet and bipolar neurons, PV was localised in large and small basket neurons and in chandelier (axoaxonic) cells, while CB immunoreactivity was present in double bouquet, Martinotti, and neurogliaform neurons. In addition, some cells in layer 1 (including Cajal-Retzius neurons) were CR immunoreactive. Calbindin immunoreactivity also labelled a population of large nonpyramidal neurons deep in the cortex. Other types of CR, PV and CB cells were also immunolabelled. A small population of layer 3 pyramidal cells was weakly CB immunoreactive. Peak cell densities occurred in layer 2/upper layer 3 for CR+ neurons and in upper to midlayer 3 for CB+ cells. PV+ neuron density peaked in midcortex. These observations support and extend a similar study of monkey prefrontal cortex (Condé et al. [1994] J. Comp. Neurol. 341:95-116). The morphologies and combined cortical depth distributions of CR+, PV+, and CB+ neurons were similar to GABA-immunolabelled cells. Local circuit neurons in mPFC displaying NADPH diaphorase activity composed less than 0.25% of the total neuron population, and were distributed in two horizontal strata, in mid- to lower layer 3 and in lower layer 5/upper layer 6. CR, PV and CB immunoreactivity was colocalised in NADPH diaphorase-reactive neurons. The interrelationships between CR+, PV+ and CB+ neurons were investigated using dual immunocytochemistry. CR+ puncta were found to be closely associated with the cell bodies and proximal processes of PV+ neurons, whereas CR+ puncta were located more distally over processes from CB+ cells. Additionally, PV+ puncta were found closely apposed to PV+ somata and processes and CR+ puncta abutted against CR+ cell bodies. The companion paper (Gabbott and Bacon [1996] J. Comp. Neurol.) presents quantitative data regarding the areal and laminar distributions of the identified cell classes in mPFC. Such data provide a realistic structural framework with which to investigate neuronal operations in monkey mPFC.

Animals↗
PubMed1988

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↗
PubMed1983

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↗
PubMed2005

Prenatal exposure to cocaine selectively disrupts the development of parvalbumin containing local circuit neurons in the medial prefrontal cortex of the rat.

Exposure to cocaine in utero can result in cognitive deficits potentially through a disruption in the inhibitory processes of the frontal cortex. One potential mechanism is through alterations in the inhibitory local circuit neurons containing the calcium-binding protein, parvalbumin. Parvalbumin-immunostaining primarily identifies 2 types of local circuit neurons: larger, rounder, axo-somal basket cells and smaller, more-spindle shaped, axo-axonic chandelier cells. Both are thought to have critical impact on the excitatory/inhibitory balance due to the proximal site of projection on pyramidal neurons. Calretinin, another calcium-binding protein, identifies a distinct sub-population of inhibitory local circuits that impinges more distally on the dendritic arbor and serves as a control population for this study. Here, we examine local circuit neurons containing either parvalbumin or calretinin in adolescent male rats (approximately 45 days old) exposed to saline or cocaine (3 mg/kg, intravenous twice a day during embryonic days 10 to 20). Prenatal cocaine exposure caused select changes in the parvalbumin, but not calretinin, containing cells in the frontal cortex. Specifically, prenatal cocaine exposure is associated with a 50% reduction in spindle-shaped parvalbumin-immunoreactive cells potentially indicating a select loss of chandelier cells or a shift to a rounder shape. Additionally, a reduction in the number of dendrites of parvalbumin-immunoreactive cells in rats exposed to cocaine in utero was noted. Other measures of both parvalbumin- and calretinin-immunoreactive cells were unchanged, including total number of cells, distribution by depth, and sizes of cells. These changes to the excitatory/inhibitory balance in the frontal cortex may contribute to the cognitive deficits associated with prenatal cocaine exposure.

Animals↗
PubMed2005

NOS-positive local circuit neurons are exclusively axo-dendritic cells both in the neo- and archi-cortex of the rat brain.

Neuronal nitric oxide synthase (nNOS)-containing neurons and axon terminals were examined in the rat somatosensory and temporal neocortex, in the CA3/a-c areas of Ammon's horn and in the hippocampal dentate gyrus. In these areas, only nonpyramidal neurons were labeled with the antibody against nNOS. Previous observations suggested that all nNOS-positive nonpyramidal cells are GABAergic local circuit neurons, which form exclusively symmetric synapses. In agreement with this, nNOS-positive axon terminals in the hippocampal formation formed symmetric synapses exclusively with dendritic shafts. In the neocortex, in contrast, in addition to the nNOS-positive axon terminals that formed synapses with unlabeled spiny and aspiny dendrites and with nNOS-positive aspiny dendrites, a small proportion of the nNOS-positive axon terminals formed symmetric synapses with dendritic spines. These results suggest that nNOS-positive local circuit neurons form a distinct group of axo-dendritic cells displaying slightly different domain specificity in the archi- and neocortex. However, nNOS-positive cells show no target selectivity, because they innervate principal cells and local circuit neurons. Afferents to the NOS-positive cells display neither domain nor target selectivity, because small unlabeled terminals formed synapses with both the soma or dendrites of nNOS-positive neurons and an adjacent unlabeled dendrite or spine in both the hippocampal formation and in neocortex.

Animals↗
PubMedDate not supplied

Dopamine innervation of a subclass of local circuit neurons in monkey prefrontal cortex: ultrastructural analysis of tyrosine hydroxylase and parvalbumin immunoreactive structures.

The ability of dopamine to regulate the cognitive functions of the prefrontal cortex (PFC) involves complex modulatory actions on GABA-containing local circuit neurons in addition to pyramidal cells. However, the subclasses of cortical neurons that receive direct dopamine input are not known. We sought to determine whether dopamine terminals innervate the subclasses of local circuit neurons that contain the calcium-binding protein parvalbumin (PV), namely the wide arbor and chandelier neurons that target pyramidal cell soma and axon initial segments respectively. Sections through area 9 of five monkeys were labeled with immunoperoxidase for tyrosine hydroxylase (TH), to identify dopamine terminals, and with immunogold-silver for PV. Electron microscopic examination of the middle cortical layers (IIIb-IV) revealed that TH-positive terminals were sometimes directly apposed to PV-labeled dendrites, and approximately one-third of these contacts exhibited morphological features that are typically associated with symmetric synapses. In contrast, TH-immunolabeled terminals in the superficial layers (I-IIIa) were less frequently apposed to PV-positive dendrites, and none of these contacts exhibited synapse-like morphology. These findings, in concert with previous studies of GABA- or calretinin-containing local circuit neurons, suggest that dopamine's modulatory action in the PFC involves selective effects on only certain interneuron populations, including those that mediate potent inhibitory actions on pyramidal cells.

Animals↗
PubMed1997

Calretinin-immunoreactive local circuit neurons in area 17 of the cynomolgus monkey, Macaca fascicularis.

The connections of local circuit neurons immunoreactive for calcium-binding protein calretinin (CR-ir) were studied in area 17 of the macaque monkey visual cortex. Most CR-ir neurons were located in layers 2 and 3A. They were polymorphic and included bitufted, multipolar, pyramid-shaped neurons with smooth dendrites and Cajal-Retzius cells. The majority of CR-ir neurons were gamma-aminobutyric acid (GABA)-immunopositive (approximately 90%), and compromised about 14% of the total GABAergic neuron population. The axons of CR-ir cells had local arbors within layers 1-3, but the major trunks descended to deep layers 5 and 6 where they formed dense terminal fields within narrow columns (100-150 microns). This specific innervation of layers 5 and 6 appeared as a distinct feature of area 17 as it was not seen in the adjacent area 18. CR-ir boutons (n = 168) were GABA-ir (95%) and formed symmetric synapses. In layers 1-3, the majority of postsynaptic targets (n = 64) were GABAergic local circuit neurons [postsynaptic target distribution: GABA-positive dendrites (67%) and somata (14%), and GABA-negative dendrites (13%) and spines (6%)]. In deep layers, the most synapses (80%; n = 187) were formed with pyramidal cells where they provided a basket-type innervation [postsynaptic target distribution: GABA-positive dendrites (19%) and somata (1%), and GABA-negative dendrites (50%), spines (20%) and somata (10%)]. Unlike other GABAergic neurons, which innervate mainly pyramidal neurons, the CR-ir subpopulation only has pyramids as a preferred target in the deep layers (layers 5 and 6); however, in the superficial layers of the area 17, selectively form synapses mainly with other GABAergic cells. Thus, the CR-ir neurons appear to have a dual function of disinhibiting superficial layer neurons and inhibiting pyramidal output neurons in the deep layers.

Animals↗
PubMedDate not supplied

A model of motor control of the nematode C. elegans with neuronal circuits.

OBJECTIVE: Living organisms have mechanisms to adapt to various conditions of external environments. If we can realize these mechanisms on the computer, it may be possible to apply methods of biological and biomimetic adaptation to the engineering of artificial machines. This paper focuses on the nematode Caenorhabditis elegans (C. elegans), which has a relatively simple structure and is one of the most studied multicellular organisms. We aim to develop its computer model, artificial C. elegans, to analyze control mechanisms with respect to motion. Although C. elegans processes many kinds of external stimuli, we focused on gentle touch stimulation. METHODS: The proposed model consists of a neuronal circuit model for motor control that responds to gentle touch stimuli and a kinematic model of the body for movement. All parameters included in the neuronal circuit model are adjusted by using the real-coded genetic algorithm. Also, the neuronal oscillator model is employed in the body model to generate the sinusoidal movement. The motion velocity of the body model is controlled by the neuronal circuit model so as to correspond to the touch stimuli that are received in sensory neurons. CONCLUSION: The computer simulations confirmed that the proposed model is capable of realizing motor control similar to that of the actual organism qualitatively. By using the artificial organism it may be possible to clarify or predict some characteristics that cannot be measured in actual experiments. With the recent development of computer technology, such a computational analysis becomes a real possibility. The artificial C. elegans will contribute for studies in experimental biology in future, although it is still developing at present.

Algorithms↗
PubMed1989

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↗
PubMedDate not supplied

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↗
PubMed1988

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↗
PubMed1999

[Hippocampal adult neurogenesis and neuronal circuit formation: an analysis with special reference to polysialic acid-neural cell adhesion molecule].

It is generally thought that neurons are generated during the embryonic and early postnatal periods, but not in the adult. However, as neurogenesis continues in the dentate granule layer of the adult hippocampal formation, this would imply that new neuronal circuits are being added to the adult hippocampus by adult neurogenesis. Since these newly generated granule cells specifically express polysialic acid (PSA)-neural cell adhesion molecule (NCAM), it is possible to examine the new neuronal circuit formed by these cells using PSA immunohistochemisty. As for PSA function, it has been shown that the PSA expression of the mossy fibers is required for synaptic arrangement. Recently neurogenesis and PSA expression in the adult hippocampus are reported to be affected by neuronal activity and hormones, suggesting that they are closely associated with hippocampal plasticity.

Animals↗
PubMed2001

Generation of a novel functional neuronal circuit in Hoxa1 mutant mice.

Early organization of the vertebrate brainstem is characterized by cellular segmentation into compartments, the rhombomeres, which follow a metameric pattern of neuronal development. Expression of the homeobox genes of the Hox family precedes rhombomere formation, and analysis of mouse Hox mutations revealed that they play an important role in the establishment of rhombomere-specific neuronal patterns. However, segmentation is a transient feature, and a dramatic reconfiguration of neurons and synapses takes place during fetal and postnatal stages. Thus, it is not clear whether the early rhombomeric pattern of Hox expression has any influence on the establishment of the neuronal circuitry of the mature brainstem. The Hoxa1 gene is the earliest Hox gene expressed in the developing hindbrain. Moreover, it is rapidly downregulated. Previous analysis of mouse Hoxa1(-/-) mutants has focused on early alterations of hindbrain segmentation and patterning. Here, we show that ectopic neuronal groups in the hindbrain of Hoxa1(-/-) mice establish a supernumerary neuronal circuit that escapes apoptosis and becomes functional postnatally. This system develops from mutant rhombomere 3 (r3)-r4 levels, includes an ectopic group of progenitors with r2 identity, and integrates the rhythm-generating network controlling respiration at birth. This is the first demonstration that changes in Hox expression patterns allow the selection of novel neuronal circuits regulating vital adaptive behaviors. The implications for the evolution of brainstem neural networks are discussed.

Animals↗
PubMed1996

Intrinsic neuromodulation: altering neuronal circuits from within.

There are two sources of neuromodulation for neuronal circuits: extrinsic inputs and intrinsic components of the circuits themselves. Extrinsic neuromodulation is known to be pervasive in nervous systems, but intrinsic neuromodulation is less recognized, despite the fact that it has now been demonstrated in sensory and neuromuscular circuits and in central pattern generators. By its nature, intrinsic neuromodulation produces local changes in neuronal computation, whereas extrinsic neuromodulation can cause global changes, often affecting many circuits simultaneously. Studies in a number of systems are defining the different properties of these two forms of neuromodulation.

Animals↗
PubMed2006

Improved organotypic cell culture model for analysis of the neuronal circuit involved in the monosynaptic stretch reflex.

Knowledge regarding neuronal circuit formation is central for the understanding of the vast network making up the brain. It is therefore necessary to find novel ways to analyze the mechanisms involved in well-defined neural circuits. We present an improved in vitro model of the monosynaptic stretch reflex circuit, based on primary organotypic cell cultures. By using limb tissue as a source of muscle fibers instead of circumspinal tissue we could make the in vitro system more in vivo like in the sense that it focuses on the stretch reflex involving limb muscles. Furthermore, our analyses showed that this procedure allows muscle fibers to follow the normal developmental pattern. Particularly interesting was the finding of slow tonic myosin heavy chain expressing muscle fibers, a developmental marker for muscle spindles, in the cultures showing that this system has the potential to contain the complete reflex circuits.

Animals↗