Biomedical subjects

H G Baumgarten

Publications and source records attributed to H G Baumgarten.

At least 19 recordsLinked to original sources

PubMed2004

Serotonin neurotoxins--past and present.

Autoxidation pathways and redox reactions of dihydroxytryptamines (5,6- and 5,7-DHT) and of 6-hydroxydopamine (6-OH-DA) are illustrated, and their potential role in aminergic neurotoxicity is discussed. It is proposed that certain aspects of the cytotoxicity of 6-OH-DA and of the DHTs, namely redox cycling of their quinone- and quinoneimine-intermediates as a source of free radicals, may also apply to quinoidal reactive intermediates and to glutathionyl- or cysteinyl conjugates ("thioether adducts") of o-dihydroxylated (catechol-like) metabolites of certain substituted amphetamines (of methylenedioxymethamphetamine (MDMA) and of methylenedioxyamphetamine (MDA)). Despite similarities in their primary interaction with the plasmalemmal (serotonergic transporter/dopamine transporter, SERT/DAT) and vesicular monoamine transporters (VMAT2), MDMA and fenfluramine (N-ethyl-meta-trifluoromethamphetamine, Fen) differ substantially in many aspects of their metabolism, pharmacokinetics, pharmacology, and neurotoxicology profile; the consequences of these differences for neuronal response patterns and long-term survival prospects are not yet fully understood. However, sustained hyperthermia appears to be a critical factor in these differences. Methodological requirements for adequate detection and description of pre- and postsynaptic forms of drug-induced neurotoxicity are exemplified using recently published accounts. The inclusion of microglial markers into research strategies has widened contemporary pathogenetic concepts on methamphetamine (MA)-induced neurotoxicity as an example of inflammatory neurodegeneration, thus complementing the traditional ROS and RNS-dependent stress models. Amphetamine-type neurotoxicity studies may assist in elaborating of preventive strategies for human neurodegenerative disorders.

Animals↗

PubMed1999

Nitric oxide synthase in skeletal muscle fibers: a signaling component of the dystrophin-glycoprotein complex.

The present review deals with the anatomical distribution, physiological importance, and pathological implications of the neuronal-type nitric oxide synthase (nNOS) in skeletal muscle. Throughout the body, nNOS is located beneath the sarcolemma of skeletal muscle fibers. In rodents, nNOS is enriched in type IIb muscle fibers, but is more homogenously distributed among type II and type I fibers in humans and subhuman primates. It is accumulated on the postsynaptic membrane at the neuromuscular junction. An increased concentration of nNOS is noted at the sarcolemma of muscle spindle fibers, in particular nuclear bag fibers, which belong to type I fibers. The association of nNOS with the sarcolemma is mediated by the dystrophin-glycoprotein complex. Specifically, nNOS is linked to alpha 1-syntrophin through PDZ domain interactions. Possibly, it also directly binds to dystrophin. The activity and expression of nNOS are regulated by both myogenic and neurogenic factors. Besides acetylcholine, glutamate has also been shown to stimulate nNOS, probably acting through N-methyl-D-aspartate receptors, which are colocalized with nNOS at the junctional sarcolemma. Functional studies have implicated nitric oxide as a modulator of skeletal muscle contractility, mitochondrial respiration, carbohydrate metabolism, and neuromuscular transmission. A clinically relevant aspect of nNOS is its absence from the skeletal muscle sarcolemma of patients with Duchenne muscular dystrophy (DMD). A concept is presented which suggests that, as a consequence of the disruption of the dystrophin-glyoprotein complex in DMD, nNOS fails to become attached to the sarcolemma and is subject to downregulation in the cytosol.

Animals↗

PubMed1998

Role of serotonin in obsessive-compulsive disorder.

BACKGROUND: Serotonin may play a role in the pathophysiology of obsessive-compulsive disorder (OCD) because of the anti-obsessional effect of selective serotonin reuptake inhibitors (SSRIs). METHOD: The literature is reviewed on knowledge of the role of serotonergic neurons in brain function, studies on monoamine metabolites in cerebrospinal fluid (CSF), various stress neuropeptides, neuroendocrine and behavioural challenge after administration of direct and indirect serotomimetic compounds, and neuroanatomical data on brain circuits organising behaviour. RESULTS: In most of the OCD cases analysed, CSF 5-hydroxyindoleacetic acid and homovanillic acid concentrations do not significantly differ from age-corrected controls. However, a relationship appears to exist between pre-treatment levels of these metabolites and clinical response to drugs acting on the serotonin transporter. Abnormalities in CSF arginine vasopressin, corticotropin-releasing hormone, oxytocin and somatostatin levels have been reported in OCD. Long-term treatment with high-doses of clomipramine, fluvoxamine, and fluoxetine tend to correct these neuropeptide abnormalities. CONCLUSIONS: We hypothesise that continuous treatment with SSRIs alters serotonin turnover and neuropeptide expression patterns in OCD-entertaining functional forebrain/midbrain circuits.

Biogenic Monoamines↗

PubMed1997

Prenatal development of the serotonin transporter in mouse brain.

The prenatal development of the serotonin transporter was analyzed in mouse brain and spinal cord by autoradiographic localization of [3H]citalopram binding. Transporter expression started at embryonic day (E) 12 in two discontinuous bands in the anterior and posterior brainstem. Labeling extended cranially and caudally, reaching the basal diencephalon at E 13, the septal complex at E 15, and the cerebral cortex at E 16. The caudal extension of the labeling descended at the ventrolateral margin of the spinal cord and reached lumbar levels at E 14. At E 17-E 18, [3H]citalopram binding emerged in the striatum, amygdaloid area, ventrobasal thalamus, paraventricular and periventricular hypothalamic nuclei, and substantia nigra. The overall spatiotemporal expression pattern of the serotonin transporter in the mouse agrees with data on the immunohistochemical localization of serotonin in the rat embryo. These results suggest that serotonergic fibers have the equipment to engage in transmitter reuptake long before synapse formation, and that transporter expression might represent a prerequesite for the developmental functions exerted by serotonin.

Animals↗

PubMed1996

Colocalisation of NADPH-diaphorase with neuropeptides in the ureterovesical ganglia of humans.

Neurones in the ureterovesical ganglion complex provide autonomic innervation to the pelvic ureter, the ureterovesical junction and the bladder trigone. We examined the distribution and peptide co-expression pattern of nitric oxide synthase (NOS) in the human ureterovesical ganglia by combining NADPH-diaphorase histochemistry with immunoreactivity for vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP). Less than 20% of nerve cells in the large ganglia of the ureterovesical complex were stained for NOS activity. In elderly individuals, ganglion cells regularly exhibited conspicuous morphological alterations suggestive of degenerative changes. Most of the NOS-positive cell bodies costained for VIP-immunoreactivity. A minority of NOS-expressing cells also reacted for NPY-immunoreactivity. CGRP-immunoreactivity was present in varicose terminal-like nerve fibres which were found to encircle NOS-containing perikarya. Occasionally, NOS-positive somata were surrounded by plexiform axon terminals which immunostained for VIP or NPY. We conclude that the passage of urine across the ureterovesical junction is under relaxatory control of a local nitric oxide/VIP(NPY) pathway which may be modulated by preganglionic efferent and/or primary afferent input.

Adult↗

PubMed1995

L-NNA inhibits the histochemical NADPH-d reaction in rat spinal cord neurons.

In nerve tissue the histochemical nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reaction is considered a suitable marker for nitric oxide synthase (NOS) activity. We have previously shown that the NOS-specific inhibitor L-nitroarginine (L-NNA) can block NADPH-d staining in intermediolateral (IML) neurons of the rat spinal cord: such a reaction might serve as a control for the presence of a NOS-related catalytic activity, i.e., L-NNA-dependent NO synthesis in these neurons. However, L-NNA inhibition of neuronal NADPH-d is inconsistent and is therefore disputed by others. This prompted us to reinvestigate the reaction conditions to provide a standardized protocol for inhibition experiments. In IML neurons of formaldehyde-fixed spinal cord tissue, inhibition of NADPH-d reaction was tested by preincubation of frozen sections with the flavin-binder diphenylene iodonium chloride (DPI, 10 microM-1 mM) which blocked the NADPH-d reaction in a concentration-dependent way, suggesting an inverse relationship of inhibitor concentration and final reaction product generated. Preincubation with the NOS-specific inhibitor L-NNA in glycine-NaOH buffer (pH 8.5-9.5) but not L-nitroarginine methyl ester (L-NAME) revealed a concentration-dependent blocking effect on neuronal NADPH-d comparable to the effects seen with DPI, suggesting the existence of a L-NNA sensitive NADPH-d activity. Blocking with L-NNA (100 microM-10 mM) was prevented by excess L-arginine (10-100 mM), suggesting competitive binding sites. NADPH-d staining was not inhibited by 7-nitro indazole, another NOS inhibitor. Thus, in formaldehyde-fixed nervous tissue both DPI and L-NNA inhibit the NOS-associated catalytic NADPH-d activity, thereby preventing NADPH-dependent conversion of nitroblue tetrazolium to formazan.

Animals↗

PubMed1995

Psychopharmacology of central serotonergic systems.

Serotonin neurons in the rostral and caudal brainstem raphe nuclear groups give rise to collateralized ascending and descending projections which provide modulatory input into most networks throughout the entire neuraxis. The rostral raphe system is interconnected with target forebrain areas through reciprocal limbic-midbrain loops, which suggests that serotonin has a role in the regulation of complex intelligent adaptive behavior. Serotonergic pathways sensitize brainstem and spinal cord central rhythmic pattern generators which organize repetitive autonomic and motor activities, e.g. oral-buccal and nutritive behaviors, facilitate tonically active motor neurons innervating antigravity muscles, and disfacilitate somatosensory information processing. Serotonin effects are mediated by multiple receptor subtypes with distinct pre- and postsynaptic localization and regional distribution pattern. They belong to the G protein superfamily, coupling to adenylate cyclase (5-HT1,4,5,6,7) or phospholipase C (5-HT2), and to the ligand-gated ion channel superfamily (5-HT3). Drugs acting at these receptors are known to modulate various aspects of cooperative social behavior and responding latency, i.e. impulsivity, in a variety of experimental models of anxiety and depression. The clinical efficacy of the so-called selective serotonin reuptake inhibitors (SSRIs) in disorders characterized by poor impulse control, e.g. bulimia nervosa, obsessive-compulsive disorder (OCD) and violent suicidal or homicidal behavior, may likewise be due to improved responding latency.

Brain↗

PubMed1995

[The role of serotonin in behavior modulation].

The central projection systems represent an expansive and important component of the brainstem reticular core which provide modulatory input into multiple target networks throughout the entire vertebrate neuraxis. Most of the afferent input into the cranial raphe originates within sensory uni- and polymodal, associative and limbic cortices suggesting that serotonin modulates preprocessed information. The serotonergic neurons discharge in a remarkably stable and tonic fashion during wakefulness. Some 5-HT neurons increase their discharge rate phasically in association with the activation of central rhythmic pattern generators involved in consummatory and grooming behaviour. In concert with enhancing motor functions, the serotonergic systems discretely deamplify sensory attentiveness and pain processing, thereby establishing an essential and protective filter mechanism against distracting and irritating noise effects of sensory afferent input level. In addition, serotonin restrains the latency to responding, i.e. impulsivity. These effects of serotonin are mediated by multiple receptor subtypes with distinct pre- and postsynaptic localisation and regional distribution pattern, acting via amplifying (5-HT2 receptors) or desamplifying (5-HT1 receptors) G-protein-dependent transduction mechanisms. The breakdown of these protective and adaptive functions of 5-HT in complex behaviour and in basic aspects of sensorimotor integration may have a pathogenetic role in disorders of impulse control (e.g. bulimia nervosa and OCD) which have been found to respond to high-dose, long-term treatment with selective serotonin reuptake inhibitors.

Animals↗

PubMed1994

Nitric oxide synthase-containing nerve fibres and neurones in the gall bladder and biliary pathways of the guinea-pig.

We investigated the distribution pattern of nitric oxide (NO) synthesizing nerve cell bodies and axons in the biliary system of the guinea-pig using immunohistochemistry for nitric oxide synthase (NOS). Nerve fibres staining for NOS were found to contact non-vascular smooth myocytes and to course beneath the epithelium. No perivascular NOS fibres were observed. The innervation density varied in different parts of the biliary tree. The lower portion of the common bile duct was more richly innervated than the remaining parts of the duct system. NOS-containing neurones encompassed a subpopulation of intramural ganglion cells. Sympathetic neurones in the coeliac ganglion were not stained. It is suggested that intrinsic NOergic neurones are involved in inhibitory motor control of the biliary musculature, including the sphincter of Oddi.

Amino Acid Oxidoreductases↗

PubMed1994

Nitric oxide synthase-containing nerve fibers and neurons in the genital tract of the female mouse.

Nitric oxide (NO) is generated intracellularly from L-arginine by the action of the enzyme nitric oxide synthase (NOS). The present investigation demonstrates immunoreactivity against NOS and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity in nerve cells and fibers of the reproductive system of the female mouse. The density of nerve fibers staining for NOS varied among different genital organs. The ovary and Fallopian tube were devoid of NOS-positive nerves. The uterine horns received sparse innervation by NOS-containing nerve fibers. The most abundant NOergic innervation was found in the uterine cervix and vagina, where the nerve fibers ran parallel to the smooth muscle bundles and beneath the epithelium; they also accompanied intramural blood vessels. The vaginal muscular wall contained single or groups of NOS-reactive nerve cells. Clusters of NOS-containing neurons were located in Frankenhäuser's ganglion at the cervico-vaginal junction. NO may therefore act as a transmitter in the nervous control of the female reproductive tract.

Amino Acid Oxidoreductases↗

PubMed1994

Nitric oxide--a novel autonomic neurotransmitter.

Considerable evidence suggests that nitric oxide (NO) acts as a nonadrenergic noncholinergic (NANC) transmitter at autonomic neuroeffector junctions. NO is generated enzymatically from L-arginine by a constitutive, cytosolic, Ca2+/calmodulin-activated NO synthase (NOS): NADPH- and tetrahydrobiopterin-dependent cytochrome P-450-type hemoprotein. Electrophysiological and pharmacological data indicate that NO fulfils most of the criteria for a neurotransmitter. It is released from axon terminals when invaded by action potentials and mimics the effect of nerve stimulation. The changes in the mechanical and/or electrical activity of smooth muscle preparations in response to transmural stimulation of NANC nerves are antagonized by inhibitors of NO synthesis or oxyhemoglobin, an NO scavenger. NO acts principally by stimulating soluble guanylate cyclase. Studies on the histochemical localization of NOS point to the involvement of the neural L-arginine-NO pathway in the regulation of vascular tone and of several aspects of respiratory, gastrointestinal, and genitourinary tract functions.

Animals↗

PubMed1994

Neurotrophy and regeneration in vivo.

Neural regeneration is a multistep event which appears to be controlled by neurotrophic factors such as neurotrophins and/or neurotrophic cytokines. Following traumatic, age- and/or disease-related responses, these molecules may be expressed and/or released by innervated target cells, neuron-ensheathing glial cells, recruited macrophages or by the neural somata themselves which altogether provide possible cues for neurotrophic strategies in vivo. In this respect, neurotrophic molecules may follow either paracrine, autocrine or even intracrine pathways in order to attenuate or even prevent neuronal degeneration. As neurotrophic molecules may have important functions as putative therapeutic agents for patients suffering from CNS disorders or from peripheral neuropathies, adequate and reliable animal lesion paradigms are of importance as in vivo assay systems. Axotomy models or selective neurotoxin-lesion models of anatomically well-defined neuron target connections are a first step towards assaying of neurotrophic actions in vivo. In lesioned central neural pathways, the existence of multineuronal networks, diffuse nuclear topography and a high degree of collateralization should be considered when studying regenerative potentials of trophic factors. Because of their simple organization and accessibility, peripheral neural pathways are particularly appealing as assay systems. As neurotrophic requirements and vulnerability vary among neural subsystems, in vivo lesion paradigms reveal pharmacological rather than physiological effects which have to be elucidated by more sophisticated experimental paradigms and molecular tools.

Animals↗

PubMed1993

Nitroxergic autonomic neurones in rat spinal cord.

We have used a polyclonal monospecific antibody to rat cerebellum nitric oxide synthase type I (NOS-I, 160 kD) in combination with reduced NADPH-diaphorase histochemical reaction (NADPH-d) to verify colocalization of both NOS protein and NOS enzymatic activity in the rat spinal cord autonomic system. Strong immunoreactivity (IR) of NOS-I was clearly detected in the four main thoracolumbar autonomic nuclei in spinal cord layers of Rexed's laminae VI, VII and X. In all labelled neurones, NOS-I-IR colocalized with NADPH-d activity, suggesting coexistence of brain-specific NOS-I-like protein and its associated enzyme activity. For these neurones the new term 'nitroxergic' (i.e. NO-generating) neurones appears to be justified. Spinal cord nitroxergic neurones are part of a NO-mediated signal transduction pathway for control of the sympathetic 'outflow' to various peripheral target organs.

Amino Acid Oxidoreductases↗

PubMed1992

Nitric oxide synthetase (NOS)-containing sympathoadrenal cholinergic neurons of the rat IML-cell column: evidence from histochemistry, immunohistochemistry, and retrograde labeling.

Nitric oxide synthetase (NOS) can be selectively stained in neurons by either NADPH-diaphorase (i.e., NOS)-histochemistry or immunohistochemistry with antibodies raised against NOS, which apparently label identical reactive sites (Hope, B.T., G.J. Michael, K.M. Knigge, and S.R. Vincent, Proc. Natl. Acad. Sci. USA 88:2811-2814, '91). We provide histochemical evidence for the existence of a neuron-specific NOS-activity in autonomic neurons of the thoracic spinal cord. Among the four main preganglionic cell clusters investigated at mid-thoracic levels, Th7-10, the intermediolateral (IML)-cell column was the most prominently stained cell group. The histochemical staining was absent in other spinal cord neurons and non-neuronal cells, e.g., GFAP-positive glial cells. Staining was completely blocked by N omega-nitro-L-arginine (L-NNA), a potent NOS-inhibitor for brain and peripheral autonomic neurons, but was still observed in the presence of another NOS-inhibitor, N omega-monomethyl-L-arginine (MeArg). The NOS-activity co-localized with nearly half of the ChAT-immunostained neurons located in the mid-thoracic IML-cell column as quantified by cell counts in single and double-stained tissue sections. We conclude that NOS-activity-containing neurons represent a distinct group among cholinergic IML-neurons, which suggests a more general function of this newly defined subpopulation of the spinal cord autonomic system. In vivo Fast blue retrograde labeling combined with histochemical staining and immunostaining revealed that sympathoadrenal projection neurons belong to the distinct NOS and ChAT-positive IML-cell group.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines↗

PubMed1992

Insulin-like growth factor-I counteracts bFGF-induced survival of nitric oxide synthase (NOS)-positive spinal cord neurons after target-lesion in vivo.

We have used nitric oxide synthase (NOS) histochemistry as a perikaryal viability marker to trace the retrograde reaction of spinal cord intermediolateral (IML) sympathoadrenal projection (SAP)-neurons to target-removal, i.e., selective adrenomedullectomy and local administration of either insulin-like growth factor-I (IGF-I), basic fibroblast growth factor (bFGF) or a combination of both. Counting of NOS-positive preganglionic spinal cord neurons 4 weeks post surgery indicated that more than 80% of stained neurons were lost from the IML-cell column. This percentage loss corresponds to the numerical loss of NOS-stained SAP-neurons labeled retrogradely with Fast-blue prior to adrenomedullectomy. Basic FGF-supplementation at the site of lesion resulted in maintenance of the majority of NOS-positive IML-neurons, a finding confirmed by the survival rate of Fast-blue prelabeled SAP-neurons. Thus, besides maintenance of the structural integrity of SAP-neurons, bFGF prevents loss of intracellular NOS-activity which may reflect unaltered cell metabolism (and function) of these neurons following target-removal in vivo. By contrast, IGF-I failed to alter the rate of disappearance of NOS-staining and labeling index of neurons within the IML-cell column postlesion, suggesting that IGF-I is not neurotrophic for SAP-neurons by itself. Combined treatment with both factors resulted in a more widespread loss of NOS-stained and Fast-blue-prelabeled SAP-neurons than registered after bFGF-only treatment. No co-trophic effect of bFGF and IGF-I was evident; rather, the pronounced bFGF-induced rescuing effect was significantly suppressed by exogenous IGF-I in vivo, supporting the idea that this or another molecule induced by the treatment enhances rather than prevents retrograde degeneration and neuronal death within the adult lesioned IML-adrenal pathway.

Adrenal Medulla↗

PubMed1992

Basic fibroblast growth factor prevents neuronal death and atrophy of retrogradely labeled preganglionic neurons in vivo.

We have used retrograde fluorescent tracing (fast blue) both before (prelabeling) and at time points after selective unilateral adrenomedullectomy in vivo (post-labeling) in order to investigate the survival and morphology of sympathoadrenal preganglionic (SAP) neurons located in the lower thoracic intermediolateral (IML) cell column of the adult rat spinal cord. By prelabeling with fast blue it was found that the majority (i.e., more than 85%) of the SAP neurons underwent degeneration and were lost from the IML cell column within 4 weeks after peripheral target lesion and administration of intramedullary gelfoam implants containing a nontrophic control protein cytochrome c. By contrast, atrophy and loss of SAP neurons was largely prevented by local treatment (intramedullary implants) with recombinant basic fibroblast growth factor (bFGF) as determined from counts of large and "healthy-looking" prelabeled neurons within the IML column ipsilateral to the lesioned (i.e., operated) side 4 weeks postimplantation. The time course of withdrawal of preganglionic axons from their lesioned target area was investigated by fast blue injections into intramedullary (control or bFGF) implants at weekly intervals postimplantation (postlabeling) and was documented by counting the number of healthy SAP neurons that retained the label. Without bFGF treatment, progressive numerical loss of SAP neurons was evident within 1 to 4 weeks postlesioning, indicative of pronounced retrograde cell degeneration. Retrograde cell degeneration was insignificant during the first 2 weeks postimplantation after early postlesion treatment with exogenous bFGF; it was apparently postponed to occur after 1 month. Implantation of gelfoam containing neutralizing anti-bFGF-antibodies resulted in accelerated retrograde axon degeneration implying that bFGF is an endogenous trophic factor for SAP neurons. The results are consistent with the idea that SAP neurons actually die following peripheral target lesion and are not supported from other trophic sources. However, these neurons can be prevented from disconnection-induced death by providing exogenous bFGF. Limited amounts of endogenous FGF may also become available to SAP axons by disintegration of nerve terminal-surrounding cells delaying the process of retrograde SAP neuron death.

Adrenal Glands↗

PubMed1992

Histochemistry of NADPH-diaphorase, a marker for neuronal nitric oxide synthase, in the peripheral autonomic nervous system of the mouse.

In order to identify possible sites of synthesis of nitric oxide in the peripheral nervous system, several mouse organs were investigated for the presence of NADPH-diaphorase activity. Diaphorase-positive neurons and fibers were localized in the tongue, submandibular salivary glands, gastrointestinal and biliary duct systems, lower urinary tract and pelvic ganglia. By thionin counterstaining it was found that a distinct subpopulation of neurons was labeled. The present study indicates that nitric oxide synthase may be present in intrinsic neurons of various organs, suggesting a widespread function of nitric oxide in the peripheral autonomic nervous system.

Amino Acid Oxidoreductases↗

PubMed1991

Olfactory bulb granule cell aggregates: morphological evidence for interperikaryal electrotonic coupling via gap junctions.

Anaxonic interneurons of the granule cell type in the mammalian main olfactory bulb (MOB) are characterized by prominent membrane specializations, which include reciprocal, interdendritic chemical and electrical synapses; however, the latter are thought to be restricted to the external plexiform layer (EPL) and connect granule-mitral- and granule-tufted-cell dendrites (Landis et al., 1974). The present study focuses on interperikaryal membrane specializations between tangentially oriented aggregates of granule microneurons in the lamina granularis interna (IGL). Both infraprimate (Rattus norvegicus, Gerbillus perpallidus) and primate species (Callithrix jacchus) were studied using the following methods: (1) transmission electron microscopy (TEM), (2) freeze-fracture analysis, (3) light and TEM immunohistochemistry using affinity-purified antibodies directed against the connexin-32 or connexin-43 carboxy tail fragment of the gap-junction protein (GJP), and (4) intracellular Lucifer yellow injections in fixed tissue (LYF technique). Freeze-fracture replicas of the MOB-IGL showed that adjacent granule cell perikarya have numerous particle aggregates on the cytoplasmic membrane; in terms of their structure and arrangement, such particles are characteristic of gap junctions. The existence of junctional membranes was substantiated by application of antibodies against GJP demonstrating punctate immunoreactivity, frequently confined to the interperikaryal plasmalemmae of granule cells in the IGL and their dendritic processes in the EPL. Upon TEM analysis, GJP-like immunoreactivity was additionally found in membranous organelles, including Golgi apparati and associated vesicular components. In order to test the permeability of identified membrane specializations, the LYF technique was used, which resulted in bright fluorescence of the perikaryal and dendritic components of the transsomatically injected neuron and staining of neighboring neurons with similar morphology. These findings imply that small molecules can diffuse across the interperikaryal membrane specializations. The existence of gap junctions between granule cell perikarya suggests that there is a significant, low-resistance electrical transmission between aggregated granule cells. This coupling might permit synchronization of neural discharge among small aggregates of these neurons. Gap junctions between granule cells may also serve signaling functions associated with the protracted period of granule cell development.

Animals↗