scholarly journals SPECIALIZED MEMBRANE JUNCTIONS BETWEEN NEURONS IN THE VERTEBRATE CEREBELLAR CORTEX

1972 ◽  
Vol 53 (2) ◽  
pp. 271-289 ◽  
Author(s):  
Constantino Sotelo ◽  
Rodolfo Llinás

"Gap" junctions, the morphological correlate for low-resistance junctions, are demonstrated between some mossy fiber terminals and granule cell dendrites in some lower vertebrate cerebella (gymnotid and frog). Most of the gap junctions (GJs) seen in the gymnotid-fish cerebellum exhibit an asymmetrical configuration, the electron-opaque cytoplasmic material underlying the junction being more extensive in the dendritic than in the axonal side. In the frog cerebellum, the GJs have a symmetrical distribution of such electron-opaque material. In both species the GJs are encountered at the same synaptic interface as the conventional synaptic zone (CSZ), constituting "mixed synapses" in a morphological sense. The axonal surface covered by CSZs is larger than that covered by GJs. In mammalian cerebellum, GJs are observed only in the molecular layer, between perikarya, dendrites, or perikarya and dendrites of the inhibitory interneurons. These GJs are intermixed with attachment plates and intermediary junctions interpreted as simply adhesive. In the mammalian cerebellum, a new type of junction which resembles the septate junctions (SJs) of invertebrate epithelia is observed between axonal branches forming the tip of the brush of basket fibers around the initial segment of the Purkinje cell axon. It is suggested that such junctions may be modified forms of septate junctions. The physiological implications of the possible existence of high-resistance cross-bridges between basket cell terminals, which may compartmentalize the extracellular space and thus regulate extracellular current flow, must be considered.

1972 ◽  
Vol 10 (3) ◽  
pp. 683-691
Author(s):  
N. E. FLOWER

The junctional complexes in the epithelia of insects of the order Dictyoptera have been investigated using the freeze-etch technique. As well as septate junctions, a new type of junction has been identified and the name ‘inverted gap junction’ proposed. The patch-like distribution of the inverted gap junctions basal to and often closely associated with septate junctions is very similar to the form of gap junctions and their relationship to tight junctions in vertebrates. This suggests that the inverted gap junctions, like normal gap junctions, could perform a communicating function between epithelial cells. The following features distinguish inverted gap junctions from normal gap junctions in freeze-etch preparations: (i) the arrays of particles and holes within inverted gap junctions appear on B- and A-type faces respectively, i.e. on the opposite faces to the particles and holes in gap junctions; (ii) the particles within inverted gap junctions appear to lie in rows which anastomose to form an irregular net, and not in an hexagonal array, as occurs in gap junctions.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Angela K Nietz ◽  
Jada H Vaden ◽  
Luke T Coddington ◽  
Linda Overstreet-Wadiche ◽  
Jacques I Wadiche

Golgi cells are the principal inhibitory neurons at the input stage of the cerebellum, providing feedforward and feedback inhibition through mossy fiber and parallel fiber synapses. In vivo studies have shown that Golgi cell activity is regulated by climbing fiber stimulation, yet there is little functional or anatomical evidence for synapses between climbing fibers and Golgi cells. Here, we show that glutamate released from climbing fibers activates ionotropic and metabotropic receptors on Golgi cells through spillover-mediated transmission. The interplay of excitatory and inhibitory conductances provides flexible control over Golgi cell spiking, allowing either excitation or a biphasic sequence of excitation and inhibition following single climbing fiber stimulation. Together with prior studies of spillover transmission to molecular layer interneurons, these results reveal that climbing fibers exert control over inhibition at both the input and output layers of the cerebellar cortex.


2000 ◽  
Vol 83 (4) ◽  
pp. 2421-2430 ◽  
Author(s):  
Yo Otsu ◽  
Eiichi Maru ◽  
Hisayuki Ohata ◽  
Ichiro Takashima ◽  
Riichi Kajiwara ◽  
...  

In the epileptic hippocampus, newly sprouted mossy fibers are considered to form recurrent excitatory connections to granule cells in the dentate gyrus and thereby increase seizure susceptibility. To study the effects of mossy fiber sprouting on neural activity in individual lamellae of the dentate gyrus, we used high-speed optical recording to record signals from voltage-sensitive dye in hippocampal slices prepared from kainate-treated epileptic rats (KA rats). In 14 of 24 slices from KA rats, hilar stimulation evoked a large depolarization in almost the entire molecular layer in which granule cell apical dendrites are located. The signals were identified as postsynaptic responses because of their dependence on extracellular Ca2+. The depolarization amplitude was largest in the inner molecular layer (the target area of sprouted mossy fibers) and declined with increasing distance from the granule cell layer. In the inner molecular layer, a good correlation was obtained between depolarization size and the density of mossy fiber terminals detected by Timm staining methods. Blockade of GABAergic inhibition by bicuculline enlarged the depolarization in granule cell dendrites. Our data indicate that mossy fiber sprouting results in a large and prolonged synaptic depolarization in an extensive dendritic area and that the enhanced GABAergic inhibition partly masks the synaptic depolarization. However, despite the large dendritic excitation induced by the sprouted mossy fibers, seizurelike activity of granule cells was never observed, even when GABAergic inhibition was blocked. Therefore, mossy fiber sprouting may not play a critical role in epileptogenesis.


1999 ◽  
Vol 81 (4) ◽  
pp. 1645-1660 ◽  
Author(s):  
Maxine M. Okazaki ◽  
Péter Molnár ◽  
J. Victor Nadler

Recurrent mossy fiber pathway in rat dentate gyrus: synaptic currents evoked in presence and absence of seizure-induced growth. A common feature of temporal lobe epilepsy and of animal models of epilepsy is the growth of hippocampal mossy fibers into the dentate molecular layer, where at least some of them innervate granule cells. Because the mossy fibers are axons of granule cells, the recurrent mossy fiber pathway provides monosynaptic excitatory feedback to these neurons that could facilitate seizure discharge. We used the pilocarpine model of temporal lobe epilepsy to study the synaptic responses evoked by activating this pathway. Whole cell patch-clamp recording demonstrated that antidromic stimulation of the mossy fibers evoked an excitatory postsynaptic current (EPSC) in ∼74% of granule cells from rats that had survived >10 wk after pilocarpine-induced status epilepticus. Recurrent mossy fiber growth was demonstrated with the Timm stain in all instances. In contrast, antidromic stimulation of the mossy fibers evoked an EPSC in only 5% of granule cells studied 4–6 days after status epilepticus, before recurrent mossy fiber growth became detectable. Notably, antidromic mossy fiber stimulation also evoked an EPSC in many granule cells from control rats. Clusters of mossy fiber-like Timm staining normally were present in the inner third of the dentate molecular layer at the level of the hippocampal formation from which slices were prepared, and several considerations suggested that the recorded EPSCs depended mainly on activation of recurrent mossy fibers rather than associational fibers. In both status epilepticus and control groups, the antidromically evoked EPSC was glutamatergic and involved the activation of both AMPA/kainate and N-methyl-d-aspartate (NMDA) receptors. EPSCs recorded in granule cells from rats with recurrent mossy fiber growth differed in three respects from those recorded in control granule cells: they were much more frequently evoked, a number of them were unusually large, and the NMDA component of the response was generally much more prominent. In contrast to the antidromically evoked EPSC, the EPSC evoked by stimulation of the perforant path appeared to be unaffected by a prior episode of status epilepticus. These results support the hypothesis that recurrent mossy fiber growth and synapse formation increases the excitatory drive to dentate granule cells and thus facilitates repetitive synchronous discharge. Activation of NMDA receptors in the recurrent pathway may contribute to seizure propagation under depolarizing conditions. Mossy fiber-granule cell synapses also are present in normal rats, where they may contribute to repetitive granule cell discharge in regions of the dentate gyrus where their numbers are significant.


1984 ◽  
Vol 51 (6) ◽  
pp. 1394-1408 ◽  
Author(s):  
L. T. Lee

In the siluroid teleost Ictalurus nebulosus, averaged evoked potentials and unit responses were recorded from various parts of the cerebellum following electrical stimulation applied to the telencephalon. Responses are most readily evoked in the cerebellum when area dorsalis pars centralis (Dc), a group of scattered large cells in the middle of the telencephalon, is stimulated. The configuration of the evoked field potentials differs according to the rate of stimulation. At a relatively low repetition rate, 0.5/s or lower, the response takes the shape of a positive wave, Pmol2, peaking at about 58 ms in the molecular layer. In the granular layer, the response is primarily a negative wave, Ngr1, followed by a slow positive deflection, Pgr3, with peak latencies of 52 and 130 ms, respectively. Ngr1 appears to be the result of summed mossy fiber-granule cell synaptic activations, with Pmol2 its concomitant passive source. No neuronal basis can be proposed for Pgr3. At higher rates of stimulation (greater than 2/S), the response to each shock is of longer latency and more complex. The stabilized waveform (i.e., after 5-9 cycles) is dominated by a surface-negative wave, Nmol, peaking at about 80 ms. The negative wave disappears at about 300 micron below the surface (slightly above the level where Purkinje cells are located) where it is replaced by a positive and negative sequence, P-Npur, peaking at about 80 and 160 ms, respectively. Both responses are bilaterally distributed but the ipsilateral responses are usually larger in amplitude and shorter in latency. Rostrocaudally, a latency gradient with longer rostral latencies is also found in both responses. To facilitate further comparative studies, the changes of peak latency and amplitude with stimulus strength of these two patterns of response were examined. Other dynamic characteristics of these two patterns of response were also examined and compared by stimulating with pairs and short trains of electric shocks. In discussing the functional implications of these findings, this telencephalocerebellar pathway appears to be a striocerebellar pathway.


Author(s):  
Rosita F. de Estable-Puig ◽  
Juan F. Estable-Puig

The granular layer of the cerebellar cortex situated between the molecular and medullary layers is built up mainly of the perikarya of small interneurons, the granule cells intermingled with part of their own processes, mossy fiber terminals, fibers of passage and other less numerous intrinsic cells. Ultrastructurally they are characterized by a nucleus which occupies most of the cell body and a rim of cytoplasm. The nucleus exhibits some aggregates of chromatin and in some cells a nucleolus. In the cytoplasm very scarce organelles are observed (Fig.l). Their main synaptic connections are found, first, at the cerebellar glomerulus where granule dendrites are seen in postsynaptic position towards mossy fiber rosettes. Desmosomic attachments are observed between granule dendrites. Second, at the level of the molecular layer where parallel fiber terminals (ramifications of the peripheral axon ) are seen apposing Purkinje dendrite spines.


1986 ◽  
Vol 84 (1) ◽  
pp. 1-17
Author(s):  
N.J. Lane ◽  
R. Dallai ◽  
P. Burighel ◽  
G.B. Martinucci

The intestinal tracts from seven different species of tunicates, some solitary, some colonial, were studied fine-structurally by freeze-fracture. These urochordates occupy an intermediate position phylogenetically between the vertebrates and the invertebrates. The various regions of their gut were isolated for examination and the junctional characteristics of each part investigated. All the species examined exhibited unequivocal vertebrate-like belts of tight-junctional networks at the luminal border of their intestinal cells. No septate junctions were observed. The tight junctions varied in the number of their component strands and the depth to which they extended basally, some becoming loose and fragmented towards that border. The junctions consisted of ridges or rows of intramembranous particles (IMPs) on the P face, with complementary, but offset, E face grooves into which IMPs sometimes fractured. Tracer studies show that punctate appositions, the thin-section correlate of these ridge/groove systems, are sites beyond which exogenous molecules do not penetrate. These junctions are therefore likely to represent permeability barriers as in the gut tract of higher chordates. Associated with these occluding zonular junctions are intermediate junctions, which exhibit no identifiable freeze-fracture profile, and macular gap junctions, characterized by a reduced intercellular cleft in thin section and by clustered arrays of P face particles in freeze-fractured replicas; these display complementary aggregates of E face pits. The diameters of these maculae are rarely very large, but in certain species (for example, Ciona), they are unusually small. In some tissues, notably those of Diplosoma and Botryllus, they are all of rather similar size, but very numerous. In yet others, such as Molgula, they are polygonal with angular outlines, as might be indicative of the uncoupled state. In many attributes, these various junctions are more similar to those found in the tissues of vertebrates, than to those in the invertebrates, which the adult zooid forms of these lowly chordates resemble anatomically.


2003 ◽  
Vol 90 (4) ◽  
pp. 2358-2366 ◽  
Author(s):  
Laura Lee Colgin ◽  
Enikö A. Kramár ◽  
Christine M. Gall ◽  
Gary Lynch

Application of the acetylcholinesterase inhibitor physostigmine to conventional hippocampal slices caused a significant reduction of field excitatory postsynaptic potentials (EPSPs) elicited by single pulse stimulation to the medial perforant path. Similar but smaller effects were obtained in the lateral perforant path and other excitatory pathways within hippocampus. The reductions were blocked by atropine, were not accompanied by evident changes in the EPSP waveform, and were eliminated by lesions to the cholinergic septo-hippocampal projections. Antidromic responses to mossy fiber stimulation, recorded in stratum granulosum, were not affected by the drug. However, paired-pulse facilitation was reliably increased, indicating that the depressed synaptic responses were secondary to reductions in transmitter release. The absence of cholinergic axo-axonic connections in the molecular layer suggests that physostigmine reduces presynaptic release by increasing retrograde signaling from the granule cells. In accord with this, an antagonist of the CB1 cannabinoid receptor eliminated the effects of physostigmine on synaptic responses, while an antagonist of the presynaptically located m2 muscarinic acetylcholine receptor did not. This is in contrast to previously reported effects involving application of cholinergic agonists, in which presynaptic inhibition likely results from direct activation of presynaptically located muscarinic receptors. In summary, it is proposed that the cholinergic inputs from the septum to the middle molecular layer modulate, via endocannabinoid release, the potency of the primary excitatory afferent of hippocampus.


1995 ◽  
Vol 82 (2) ◽  
pp. 220-227 ◽  
Author(s):  
Gary W. Mathern ◽  
James K. Pretorius ◽  
Thomas L. Babb

✓ The type of initial precipitating injury and the age at which it occurred in 20 patients with nonlesional temporal lobe epilepsy (TLE) were related to clinical features, presurgical neuroimaging, quantified hippocampal pathologies, and seizure outcomes. Clinical data, neuroimaging records, and seizure outcomes were abstracted from medical records and confirmed with patient and family contacts. Hippocampal neuron losses and mossy fiber reactive synaptogenesis were quantified independently. Results showed that the type of initial precipitating injury and the patient's age at which it occurred were related to the clinicopathological features of TLE. An initial precipitating injury occurred in 18 patients (90%), all of whom had mesial temporal sclerosis (MTS). Patients with a prolonged initial seizure or a nonseizure initial precipitating injury before age 5 years were significantly more likely to have unilateral hippocampal atrophy (p < 0.05) shown on magnetic resonance (MR) imaging, and had significantly greater inner molecular layer mossy fiber puncta densities (p < 0.001) than patients with nonprolonged childhood initial precipitating injuries and/or seizures after age 5 years. Furthermore, nonseizure injuries in patients before age 5 years had significantly longer latent periods (p < 0.05), and the patients did not respond to surgical treatment as well as other MTS patients. Those with an initial precipitating injury after age 5 years had MTS but showed significantly less inner molecular layer mossy fiber sprouting (p < 0.05) than patients whose injuries appeared before age 5 years. Patients without an initial precipitating injury (idiopathic TLE) had significantly fewer neuron losses (p < 0.05) and inner molecular layer mossy fiber puncta densities (p < 0.05) and had worse outcomes following en bloc temporal lobectomy compared to patients with MTS who had experienced initial precipitating injuries. Patients with unilateral hippocampal abnormalities on MR imaging did not show significant differences in neuron losses or aberrant mossy fiber puncta densities compared to patients without asymmetry. These results support the hypothesis that the type of initial precipitating injury and the age at which the injury occurred initiates and influences the pathophysiological process that eventually develops into MTS. These data support the notion that the pathophysiology of hippocampal damage and mossy fiber sprouting after an initial precipitating injury may be a progressive process.


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