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PubMed2004

Spatial analysis reveals alterations of parvalbumin- and calbindin-positive local circuit neurons in the cerebral cortex of mutant mdx mice.

The aim of the present study was to investigate the spatial organization of selected populations of local circuit neurons in the cerebral cortex of the mutant mdx mouse, an acknowledged model of Duchenne Muscular Dystrophy. To this purpose, we quantified and compared the distribution of parvalbumin- and calbindin-positive neurons in the motor, somatosensory, visual, and anterior cingulate cortices of wild-type and mdx mice. The methodological approach was based on generation of two-dimensional Voronoi polygons from digital charts of the cell populations visualized immunohistochemically. Polygon areas were then analyzed and the derived coefficients of variation were statistically compared. Using this strategy, we were able to reveal, in mdx mice, changes involving both the above populations of interneurons. These changes were evident in the motor and anterior cingulate cortices but not in the somatosensory and visual cortices. In addition, the changes of coefficients of variation were area-specific in the cortex of mdx mice. The values increased in the motor cortex and decreased in the anterior cingulate cortex with respect to the corresponding values of wild-type animals. The present findings point out widespread alterations in the mdx cortex involving also areas not primarily related to sensorimotor integration. In addition, we demonstrate that cortical alterations of the local circuit machinery are characterized in mdx mice by individual regional differences.

Animals↗
PubMed1997

Local circuit neurons of macaque monkey striate cortex: IV. Neurons of laminae 1-3A.

We continue our Golgi studies (Lund [1987] J. Comp. Neurol. 257:60-92; Lund et al. [1988] J. Comp. Neurol. 276:1-29; Lund and Yoshioka [1991] J. Comp. Neurol. 331:234-258) of the organization of local circuit, largely gamma-aminobutyric acid (GABA)-containing neurons in macaque monkey visual cortex, area V1, with this account of the local circuit neurons lying in layers 1 and 2/3A. These layers receive intrinsic interlaminar excitatory and inhibitory relays from layers 3B, 4A, 4B, and 5. We describe seven varieties of local circuit neurons with somata within layers 1-2/3A, and we compare the lateral scale of spread of the axons and dendrites of these neurons with the size of the columnar connectional patch domains made by the laterally spreading axon collaterals of pyramidal neurons within the superficial layers (Lund et al. [1993] Cerebral Cortex 3:148-162). We conclude from this comparison that all of the neurons have dendritic fields that are limited to single patch domains. Furthermore, only two of the seven local circuit neuron varieties have sufficient axon spread to influence territory beyond single domains, reaching into neighboring territory likely to differ in function from that occupied by their dendrites. We have identified descending projections from particular varieties to layers 3B, 4A, 4B, and 5 and to the white matter. We discuss the contributions that these interneurons may make to function within the superficial cortical layers, and we summarize our overall conclusions, so far, from our set of studies on interneurons within area V1 of the macaque.

Animals↗
PubMedDate not supplied

Migration of peptide-immunoreactive local circuit neurons to rat cingulate cortex.

The times of origin of neurons immunoreactive for somatostatin (SRIF), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were determined using a combined immunohistochemical-autoradiographic technique. 3H-thymidine (3H-dT) was injected into pregnant rats on gestational day 13 (G13), G15, G17, G19, or G21. Animals were killed on postnatal day 30, that is, after the completion of neuronal migration. Sections of the brain including posterior cingulate cortex (area 29), visual cortex (area 17), and somatosensory cortex (area 3) were processed serially for peptide immunoreactivity and autoradiographically for labeling with 3H-dT. SRIF- and CCK-immunoreactive neurons were cogenerated and comigrated according to an inside-to-outside sequence. Accordingly, neurons in layer VI were born on G13, neurons in intermediate layers were born on G15-G17, and neurons in layer II/III were born on G19-G21. In contrast, VIP-positive neurons did not follow such a sequence. Neurons in all layers of cortex were generated at relatively constant rates between G13 and G21. VIP-immunoreactive neurons were the only known subpopulation of neurons that did not migrate into cortex by an inside-to-outside sequence. Thus, the migration of local circuit neurons to cingulate cortex follows patterns that are similar to those discerned in more differentiated cortical areas.

Animals↗
PubMed1997

Local-circuit neurones in the medial prefrontal cortex (areas 25, 32 and 24b) in the rat: morphology and quantitative distribution.

This paper is a light microscopical study describing the detailed morphology and quantitative distribution of local circuit neurones in areas 25, 32, and 24b of the medial prefrontal cortex (mPFC) in the rat. Cortical interneurones were identified immunocytochemically by their expression of calretinin (CR), parvalbumin (PV), and calbindin D-28k (CB) immunoreactivity. Neurones immunoreactive for gamma-aminobutyric acid (GABA) were also investigated, as were interneurones containing reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity. Several distinct classes of CR+, PV+, and CB+ neurones were identified; the most frequent were: bipolar/bitufted CR+ cells in upper layer 3; multipolar PV+ neurones in layers 3 and 5; and bitufted/multipolar CB+ neurones in lower layer 3. CB+ neurones resembling Martinotti and neurogliaform cells were also present in layers 5/6. The morphologies and depth distributions of each cell type were consistent across the three areas of mPFC studied. Seven classes of diaphorase-reactive mPFC neurone are described; these cells were composed about 0.8% of the total neurone population and had a peak distribution located in mid- to lower layer 5 in each area. In areas 32 and 25, three defined bands of diffuse NADPH diaphorase staining were located in layer 2 and in upper and deep layer 5. Diaphorase reactivity was very infrequently colocalised with either CR, PV, or CB immunoreactivities. The numerical densities of neurones (N(V), number of cells per mm3) in each layer were calculated stereologically. The mean total neuronal N(V) estimate for areas 25, 32, and 24b was 51,603 +/- 3,324 (mean +/- S.D.; n = 8). Significant interareal differences were detected. From cortical thickness data and neuronal N(V) estimates, the absolute number of neurones under 1 mm2 of cortical surface (N(C)) have been derived. The mean N(C) value for areas 25, 32, and 24b was 57,328 +/- 7,505 neurones. In immunolabelled Nissl-stained sections, CR+ neurones constituted an overall 4.0%, PV+ cells 5.6%, and CB+ 3.4% of the total neurone populations in mPFC. GABA+ cells represented a mean of 16.2% (14.8-17.2%) of neurones in areas 25, 32 and 24b. The absolute numbers of CR+, PV+, CB+, and GABA+ neurones within individual layers in a column of cortex under 1 mm2 of cortical surface (N(L)) have also been derived, with significant interareal differences in N(L) values being detected. The data provide the structural basis for a qualitative and quantitative definition of local cortical circuits in the rat mPFC.

Animals↗
PubMed1996

Local circuit neurons in the medial prefrontal cortex (areas 24a,b,c, 25 and 32) in the monkey: II. Quantitative areal and laminar distributions.

The companion paper (Gabbott and Bacon [1996] J. Comp. Neurol.) describes the morphology of calretinin (CR)-, parvalbumin (PV)-, calbindin (CB)-, and GABA-immunoreactive neurons, and NADPH diaphorase-reactive cells, in the medial prefrontal cortex (mPFC; areas 24a, 24b, 24c, 25 and 32) of the adult monkey. Since these local circuit neurons play crucial functional roles, the aim of this study was to provide supportive quantitative data defining their areal and laminar distribution in mPFC. The numerical densities of neurons (Nv, number of cells per mm3) in each area and layer were calculated stereologically. The mean total neuronal NV estimates across mPFC was 55,727 +/- 3,319 per mm3 (mean +/- S.D.; n = 3); values ranged from 50,489 +/- 8,374 per mm3 (area 24a) to 59,938 +/- 7,214 per mm3 (area 24c). Interareal differences were not significant. Cortical depth measurements and neuronal NV estimates for each area allowed the absolute number of neurons in a column of cortex under 1 mm2 of surface to be calculated; values varied between 86,457 +/- 15,063 (area 24a) and 128,464 +/- 24,050 (area 24c). Using immunolabelled Nissl-stained sections of mPFC, CR+ neurons constituted 11.2%, PV+ neurons 5.9%, and CB+ neurons 5.0% of the total neuron population. GABA+ neurons represented an overall 24.9% (23.5-27.3%) of neurons in the mPFC. Differences between areas were not significant. The cortical depth distribution histograms of CR+, PV+, CB+, and GABA+ cell populations in each area were derived and the percentage of a given cell population in each layer subsequently calculated. Peaks in the cortical depth distributions of CR+ and CB+ neurons occurred in layer 2 and upper layer 3, respectively; the peak distribution of PV+ neurons occurred between lower layer 3 and upper layer 5. The depth distribution of GABA+ cells reflected the combined distributions of CR+, PV+ and CR+ neurons. In all areas, the majority (74.4-84.0%) of the GABA cell population was located in layers 2/3. The depth distributions for each cell type were similar between areas. Diaphorase-reactive neurons accounted for 0.25% (0.2-0.32%) of all cortical neurons in mPFC and were distributed in two horizontal strata, in midlayer 3 and in mid/upper layer 6. A large population of diaphorase-reactive cells was present in the white matter. The absolute numbers of CR+, PV+, CB+ and GABA+ neurons within individual layers in a column of cortex under 1 mm2 and 50 x 50 microns of cortical surface have been derived. The data presented provide the basis for a quantitative definition of cortical circuits in monkey mPFC.

Afferent Pathways↗
PubMed1999

The evolution of neuronal circuits underlying species-specific behavior.

The nervous system is evolutionarily conservative compared to the peripheral appendages that it controls. However, species-specific behaviors may have arisen from very small changes in neuronal circuits. In particular, changes in neuromodulatory systems may allow multifunctional circuits to produce different sets of behaviors in closely related species. Recently, it was demonstrated that even species differences in complex social behavior may be attributed to a change in the promoter region of a single gene regulating a neuromodulatory action.

Animals↗
PubMed1987

Local circuit neurons in the rat ventrobasal thalamus--a GABA immunocytochemical study.

The ventrobasal thalamus of seven rats was processed for immunocytochemistry using antisera to glutamate decarboxylase or gamma-aminobutyrate (GABA). Glutamate decarboxylase-stained sections showed a network of stained fibers and terminals but no stained cell bodies. GABA-stained sections had fewer stained fibers and terminals but did show a few stained cell bodies. Cell bodies were especially apparent when carbazole was used for a chromogen for the peroxidase-antiperoxidase visualization. The GABA-stained cells were found to be distributed throughout the ventrobasal complex, to have smaller soma cross-sectional areas than most other cells (81 +/- 34 microns vs 105 +/- 36 microns for all cells) and to make up 0.4 +/- 0.3% of the neuronal population of the ventrobasal complex. Injections of horseradish peroxidase into the somatosensory cortex (SI) retrogradely filled many neurons in the ventrobasal thalamus, but none of these labeled neurons were double labeled with GABA. These results indicate that the GABA-labeled cells probably represent a small population of local circuit neurons in the rat ventrobasal thalamus.

Animals↗
PubMed1999

Local circuit neurons showing calbindin D28k-immunoreactivity in the substantia gelatinosa of the medullary dorsal horn of the rat. An immunohistochemical study combined with intracellular staining in slice preparation.

Calbindin D28k (CB)-immunoreactive local circuit neurons in the substantia gelatinosa of the rat medullary dorsal horn were studied in slice preparations; intracellular injection of biocytin was followed by histochemical visualization of biocytin, then CB immunohistochemistry was performed. In six neurons so far examined, overall morphology, including those of dendritic fields, axonal fields, and arborization patterns, was common.

Animals↗
PubMed1995

Co-localisation of NADPH diaphorase activity and GABA immunoreactivity in local circuit neurones in the medial prefrontal cortex (mPFC) of the rat.

This study provides evidence that neurones in the medial prefrontal cortex of the rat (mPFC areas 24b, 25, and 32) containing strong NADPH diaphorase reactivity also contain GABA immunoreactivity. Also demonstrated is the co-localisation of NADPH diaphorase activity with immunoreactivity for the neuronal isoform of nitric oxide synthase (nNOS) in mPFC neurones. Qualitative and quantitative analyses in the light and electron microscopes indicate that strongly NADPH diaphorase reactive cells are a subpopulation of GABAergic local circuit neurones and constitute a very small proportion (0.6-1.1%) of neurones in rat mPFC. These results suggest that NADPH diaphorase reactive cells in rat mPFC can influence neural activity via GABA-mediated and NO-mediated mechanisms.

Animals↗
PubMed2003

The neuronal circuit of augmenting effects on intrinsic laryngeal muscle activities induced by nasal air-jet stimulation in decerebrate cats.

We previously demonstrated that during nasal air-jet stimulation, both the activities of intrinsic laryngeal adductor and abductor muscles persistently increase, whereas the respiratory cycle prolongs and the activity of diaphragm decreases [Am. J. Rhinol. 9 (1995) 203-208; Neurosci. Res. 31 (1998) 137-146]. The purpose of this study was to clarify the neuronal circuit underlying the augmentation of intrinsic laryngeal muscles evoked by nasal air-jet stimulation. The immunohistologic analysis of Fos-expression was reported to determine the distribution of activated neurons in cat brainstem evoked by sneeze-inducing air puff stimulation of the nasal mucosa [Brain Res. 687 (1995) 143-154]. In sneezing cats, immunoreactivity was evoked in projection areas of the ethmoidal afferents, e.g. the subnuclei caudalis, interpolaris and in interstitial islands of the trigeminal sensory complex. Immunoreactivity was also enhanced in the solitary complex, the nucleus retroambiguus, the pontine parabrachial area and the lateral aspect of the parvocellular reticular formation [Brain Res. 687 (1995) 143-154]. In the present study, we focussed on the parvocellular reticular nucleus (PRN) as a relay of the neural circuit contributed to the augmentation of intrinsic laryngeal muscles evoked by nasal air-jet stimulation. We recorded the neuronal behavior of PRN during the nasal air-jet stimulation in precollicular-postmammillary decerebrate cats. As the results, 24% (17/71) of recorded neurons which were activated orthodromically by the electrical stimulation to anterior ethmoidal nerve, increased their firing rates in response to the nasal air-jet stimulation. Furthermore, spike-triggered averaging method revealed that four of these 17 PRN neurons activated intrinsic laryngeal muscles, suggesting that such neurons have excitatory projections to the intrinsic laryngeal muscle motoneurons in the nucleus ambiguus. These results suggest that the some of PRN neuron play a role in augmentation of the intrinsic laryngeal muscles activities during nasal air-jet stimulation.

Action Potentials↗
PubMed2004

[Neuronal circuits of reading and writing in Japanese language].

Japanese writing system consists of two different types of letters, kana (phonogram) and kanji (morphogram). Various types of alexia with or without agraphia in the Japanese language cause specific type of kanji/kanja dissociation. Upon the neuropsychological analysis of these dissociations, we have proposed a hypothesis of dual neuronal circuits of reading and writing process. Subsequent PET activation studies upon normal subjects confirmed the hypothesis; semantic reading pathway via area 37 on the inferior border of the left temporal lobe and phonological reading pathway via middle portion of the left lateral occipital lobe.

Agraphia↗
PubMed1994

Morphological and physiological bases of crayfish local circuit neurones.

As the subject of neuroethological studies, arthropods offer several advantages to elucidate the neural processes that generate and control behavioural acts. The relative simplicity of their neural organization and their identifiable neurones are particularly advantageous. The crayfish, Procambarus clarkii, uropods are paired appendages of the last abdominal segment that show bilateral closing movement in response to mechanical stimulation. This movement, the avoidance "dart" response, is mediated by a cascade and parallel organization of local circuit neurones in the terminal abdominal ganglion. Thirty intersegmental ascending interneurones and 20 spiking local interneurones have been identified both morphologically and physiologically. They receive exteroceptive inputs directly from the sensory afferents. Two complementary groups of unilateral nonspiking local interneurones have also been functionally identified. They exert fine control over the wide range of activity of motor neurones in a graded and sustained manner. These nonspiking interneurones form opposing and parallel pathways that are essential in modulating the pattern of movement of the uropods.

Animals↗
PubMed1993

A high degree of spatial selectivity in the axonal and dendritic domains of physiologically identified local-circuit neurons in the dentate gyrus of the rat hippocampus.

The axonal and dendritic domains of neurons with extensive, locally arborizing axons were delineated in the dentate gyrus of the rat hippocampus. In horizontally cut slice preparations neurons were briefly recorded and subsequently filled with biocytin when one or several of the following physiological properties were observed: (i) high-amplitude short-latency spike afterhyperpolarization; (ii) lack of spike frequency adaptation; (iii) high firing rate in response to depolarizing current. In a sample of 14 neurons, sufficient dendritic and/or axonal detail was recovered to identify them as non-principal cells, i.e. non-granule, non-mossy cells. Five distinct types of cells were recognized, based on the spatial distribution of dendrites, presumably reflecting the availability of afferents, and on the basis of the highly selective distribution of their axon terminals, indicating synaptic target selectivity. They are: (1) the hilar cell forming a dense axonal plexus in the commissural and association pathway terminal field (HICAP cell; horizontal axon extent 1.6 mm) in the inner one-third of the molecular layer, and having dendrites extending from the hilus to the top of the molecular layer; (2) the hilar cell with its axon ramifying in the perforant path terminal field (HIPP cell, horizontal axon extent 2.0 mm) in the outer two-thirds of the molecular layer, whereas its spiny dendrites were restricted to the hilus; (3) the molecular layer cell with its dendritic and axonal domains confined to the perforant path terminal zone (MOPP cell, horizontal extent of axon 2.0 mm); (4) the dentate basket cell (horizontal axon extent 0.9 mm) had most of its axon concentrated in the granule cell layer, the remainder being localized in the inner molecular layer and hilus; (5) the hilar chandelier cell, or axo-axonic cell (horizontal axon extent 1.1 mm), densely innervating the granule cell layer with fascicles of radially oriented terminal rows, and also forming an extensive plexus in the hilus. The three cell types having their somata in the hilus projected to granule cells at the same septo-temporal level where their cell bodies were located. The results demonstrate that there is a spatially selective innervation of the granule cells by at least five distinct types of dentate neurons, which terminate in several instances in mutually exclusive domains. Their dendrites may have access to all (HICAP cell) or only a few (e.g. HIPP and MOPP cell) of the hippocampal afferents. This arrangement provides a framework for independent interaction between the output of local circuit neurons and subsets of excitatory afferents providing input to principal cells.

Animals↗
PubMed2002

Reelin immunoreactivity in the adult primate brain: intracellular localization in projecting and local circuit neurons of the cerebral cortex, hippocampus and subcortical regions.

Reelin is a large secretable protein which is widely expressed by specific neuronal populations. In the embryonic brain, Reelin plays a signaling role critical for the correct positioning of migrating neuroblasts. Reelin is also expressed in the adult mammalian brain, including humans; however, its function/s there remain poorly understood. To gain insight into which neuronal populations and specific circuits may be influenced by Reelin in the adult, we have conducted a light and electron microscope analysis of Reelin-immunoreactive neuron types in the cerebral cortex and subcortical regions of adult macaque monkeys. Results show that the great majority of brain neurons, including interneurons and projection neurons, are immunoreactive for Reelin although some neuronal populations do not contain Reelin. The immunoreactive protein is located intracellularly, mainly in neuronal somata. Reelin is also present in gray matter neuropil as well as in some long axonal pathways and their terminal arborizations, suggesting that it can be axonally transported over long distances. The staining patterns in the labeled neurons are remarkably diverse. Our observations reveal a wider distribution of Reelin in the adult macaque brain than in any other species investigated to date. The data show that Reelin is in a position to influence most brain circuits in the adult primate brain.

Animals↗
PubMed1986

Synaptic connections of relay and local circuit neurons in the monkey's dorsal lateral geniculate nucleus.

The synaptic inputs to a single neuron's dendritic tree can be analyzed using electronmicroscopic reconstructions after intracellular injections of horseradish peroxidase. In the monkey's dorsal lateral geniculate nucleus, the proximal dendrites of magnocellular and parvocellular relay cells received retinal synapses and inhibitory synapses, while the intermediate and distal dendrites received cortical synapses. A local circuit neuron had both similar synaptic inputs and similar physiology to parvocellular relay neurons, but additionally had presynaptic dendrites and no axon. These results provide a wiring diagram for the neuronal types in this nucleus.

Animals↗
PubMed2006

Amygdala input monosynaptically innervates parvalbumin immunoreactive local circuit neurons in rat medial prefrontal cortex.

The projection from the basolateral nucleus of the amygdala (BLA) conveys information about the affective significance of sensory stimuli to the medial prefrontal cortex (mPFC). By using an anterograde tract-tracing procedure combined with immunocytochemistry and correlated light/electron microscopical examination, labeled BLA afferents to layers 2-6 of the rat mPFC are shown to establish asymmetrical synaptic contacts, not only with dendritic spines (approximately 95.7% of targets innervated), but also with the aspiny dendritic shafts and somata of multipolar parvalbumin immunopositive (PV+) neurons. A population of PV- dendritic shafts was also innervated. Labeled BLA synaptic input to identified PV+ structures occurred in layers 2-6 of mPFC. The results indicate that labeled BLA afferents predominantly contact the spiny processes of presumed pyramidal cells and also provide a direct and specific innervation to a sub-population of local circuit neurons in mPFC containing PV. Since PV+ cells include two significant classes of fast-spiking GABAergic inhibitory interneuron (basket and axo-axonic cells), these novel observations indicate that the amygdalocortical pathway in the rat has the ability to directly influence functionally strategic 'feed-forward' inhibitory mechanisms at the first stage of processing amygdalocortical information.

Afferent Pathways↗
PubMed2005

Antidepressant-elicited changes in gene expression: remodeling of neuronal circuits as a new hypothesis for drug efficacy.

Although antidepressants have been used clinically for more than 50 years, no consensus has been reached concerning their precise molecular mechanism of action. Pharmacogenomics is a powerful tool that can be used to identify genes affected by antidepressants or by other effective therapeutic manipulations. Using this tool, others and we have identified as candidate molecular targets several genes or expressed sequence tags (ESTs) that are induced by chronic antidepressant treatment. In this article, we review antidepressant-elicited changes in gene expression, focusing especially on the remodeling of neuronal circuits that results. This refocusing motivates our hypothesis that this plasticity represents the mechanism for drug efficacy, and thus a causal event for clinical improvement. Defining the roles of these molecules in drug-induced neural plasticity is likely to transform the course of research on the biological basis of antidepressants. Such detailed knowledge will have profound effects on the diagnosis, prevention, and treatment of depression. Consideration of novel biological approaches beyond the "monoamine hypothesis" of depression is expected to evoke paradigm shifts in the future of antidepressant research.

Animals↗