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Results for “CEREBELLAR CORTEX”

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PubMed1980

Myelinated dendrites of Purkinje cells in deafferented cerebellar cortex.

Following chronical (30--60 days) isolation of cerebellar vermis in developing and in adult rats, partially myelinated primary and secondary dendrites of Purkinje cells and myelinated Golgi, basket and stellate cell bodies were observed. The dendritic myelin sheaths were not continuous with but developed independently of preexisting axonal myelin. Experiments on rats and cats have additionally revealed that this redundant myelinization of Purkinje dendrites and of interneuronal perikarya can be elicited also by selective destruction of the olivocerebellar (climbing fibre) afferents, indicating a direct influence of climbing fibre afferentation on myelinization processes in the cerebellar cortex.

Afferent Pathways↗

PubMed2003

Spatial patterns of the pathological changes in the cerebellar cortex in sporadic Creutzfeldt-Jakob disease (sCJD).

The spatial patterns of the vacuolation ("spongiform change"), surviving cells, and prion protein (PrP) deposition were studied in the various cell laminae of the cerebellar cortex in 11 cases of sporadic Creutzfeldt-Jakob disease (sCJD). Clustering of the histological features, with the clusters regularly distributed along the folia, was evident in all cell laminae. In the molecular layer, clusters of vacuoles coincided with the surviving Purkinje cells. In the granule cell layer, however, the spatial relationship between the vacuoles and surviving cells was more complex and varied between cases. PrP deposition was not spatially correlated with either the vacuoles or the surviving cells in any of the cerebellar laminae in the majority of cases. In some cases, there were spatial relationships between the histological features in the molecular and granule cell layers. The data suggest that degeneration of the cerebellar cortex in sCJD may occur in a topographic pattern consistent with the spread of prion pathology along anatomical pathways. The development of the vacuolation may be an early stage of the pathology in the cerebellum preceding the appearance of the PrP deposits. In addition, there is evidence that the pathological changes may spread across the different laminae of the cerebellar cortex.

Aged↗

PubMed2003

[Unipolar brush cells--a new type of excitatory interneurons of the cerebellar cortex and brainstem cochlear nuclei].

This review summarizes the literature data and the results of the authors' own investigations on morphology, neurochemical specialization, and spatial organization of unipolar brush neurons (UBN) in the cerebellar cortex and brainstem cochlear nuclei. UBN represent excitatory interneurons with a single dendrite that forms a compact brush-like branching in its terminal part. They are distributed non-uniformly in the granular layer of the cerebellar cortex and are localized predominantly in its vestibular areas. UBN synthesize glutamate, calretinin, contain metabo- and ionotropic glutamate receptors. Dendritic brush of UBN forms the giant synapses with the rosettes of glutamate- and cholinergic afferent mossy fibers. Axons of UBN form intracortical system of mossy fibers, which, by forming rosettes and glomeruli, make contacts with dendrites of similar cells and those of the granular cells. In the chain of inerneuronal communications, UBN may be regarded as the intermediate link, which amplifies the excitatory effect of the afferent mossy fibers upon granular cells of the cerebellar cortex and brainstem cochlear nuclei.

Animals↗

PubMed1983

Congruence of spatial organization of tactile projections to granule cell and Purkinje cell layers of cerebellar hemispheres of the albino rat: vertical organization of cerebellar cortex.

1. We compared the spatial pattern of shortest latency somatosensory (tactile) projections to the Purkinje cell (PC) layer and to the underlying granule cell (GC) layer in tactile areas of rat cerebellar cortex. Micro-mapping methods were used to sample single units in the PC layer and multiple units in the GC layer of both anesthetized and unanesthetized rats. Mechanical and electrical stimulation of the body surface were employed. Responsiveness of PCs to cutaneous stimulation was assessed by constructing histograms of simple spike activity and statistically comparing poststimulus activity to nonstimulated base-line PC activity. 2. We found that PCs respond to tactile stimulation with increases (7-10 ms) followed by decreases (8-15 ms) in simple spike activity. Increases in simple spike activity followed activation of the underlying GC layer by 1-4 ms, while decreases in simple spike activity were found 2-5 ms after GC layer activation. 3. PCs were found to have both excitatory and inhibitory receptive fields (RFs). Excitatory RFs were restricted to small areas of a single body part and for each PC were very similar or identical to the RFs of neurons in the immediately subjacent GC layer. Inhibitory PC RFs were larger, often containing more than one body part and for each PC, were only partially similar to the RFs of subjacent GCs. PC inhibitory RFs also often included body surfaces projecting to the nearby but not to the underlying GC layer. 4. Stimulation of a single peripheral locus resulted in small, distinct regions of PC layer excitation and inhibition. Areas of PC excitation overlie activated regions of the GC layer, while inhibited PCs overlie both activated and nonactivated GC regions. 5. We found PCs to be organized in groups or patches with respect to the specific body region that was capable of activating them (upper lip, lower lip, etc.). Adjacent patches of PCs often represented widely separated body parts. This pattern of PC layer activating RF projections was congruent with the pattern of excitatory RF projections to the underlying GC layer. 6. These results indicate that there is a vertical organization in GC-PC excitatory relations, while GC-induced PC inhibition is slightly more widely distributed. 7. Our finding that the patchlike activation of PCs is congruent with that of the underlying GC layer contrasts with the classical concept that PCs are activated by parallel fibers in a "beamlike" fashion from a patch of GCs. Thus, a reevaluation of the role of parallel fibers seems to us to be in order. 8. In conclusion, our results support the view that short-latency afferent tactile projections to both the GC and PC layers of cerebellar cortex are highly organized spatially. This specificity of body surface projections must be incorporated into modern views of the functional organization of cerebellar cortex.

Animals↗

PubMed1995

Light-microscopic distribution and parasagittal organisation of muscarinic receptors in rabbit cerebellar cortex.

Recent studies on the effects of intrafloccular injections of muscarinic agonists and antagonists on compensatory eye movements in rabbit, indicate that muscarinic receptors may play a modulatory role in the rabbit cerebellar circuitry. It was previously demonstrated by Neustadt et al. (1988), that muscarinic receptors in rabbit cerebellar cortex are distributed into alternating longitudinal zones of very high and very low receptor density. In the present study, the zonal and cellular distribution of muscarinic receptors in the rabbit cerebellar cortex is investigated in detail using in vitro ligand autoradiography with the non-selective high-affinity antagonist [3H]quinuclidinyl benzilate (QNB), and the M2-specific antagonist [3H]AF-DX384, and immunocytochemistry with a monoclonal antibody specific for the cloned m2 muscarinic receptor protein. [3H]QNB and [3H]AF-DX384 binding sites and m2-immunoreactivity had similar overall distributions: dense labeling occurred in the dendritic arbors of a subset of Purkinje cells that are organized into parasagittal bands. A high level of muscarinic receptor labeling was also observed in a thin substratum of the molecular layer immediately above the Purkinje cell layer of the vestibulo-cerebellar lobules, i.e. the nodulus, the ventral uvula and the flocculus. Labeling in this stratum was associated with densely packed fibres, which were putatively identified as parallel fibres. Also Golgi cells, which were localized in part in the molecular layer, and a subset of mossy fibre rosettes, primarily concentrated in lobule VI, were immunoreactive for the m2 receptor. The parasagittal band of labeled Purkinje cell dendrites were most prominent in the anterior lobe (lobules I-V), in crus 1 and 2, in the flocculus, the ventral paraflocculus and the rostral folium of the nodulus. In other lobules, only infrequent Purkinje cells contained muscarinic receptors. The parasagittal organisation of muscarinic receptors differed from that of zebrin I, a Purkinje cell-specific protein which is often used as a marker of parasagittal parcelation of the cerebellar cortex. In the anterior lobe, however, there was a partial correspondence between muscarinic receptor and zebrin I bands. In the flocculus the distribution of muscarinic-receptor-positive Purkinje cells was related to the distinct white matter compartments as revealed with acetylcholinesterase (AChE) histochemistry. Muscarinic receptor-containing Purkinje cells were located primarily in the floccular zone 1, which is implicated in the control of eye movements about a horizontal axis. In order to relate the distribution of muscarinic receptor labeling to that of cholinergic nerve terminals, [3H]QNB binding sites and sodium-dependent [3H]hemicholinium-3 binding were compared. Sodium-dependent [3H]hemicholinium-3 binding sites mainly occurred in the granule cell layer of the vestibulo-cerebellum, which corresponds well with the distribution of the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT). However, sodium-dependent [3H]hemicholinium binding complemented, rather than co-localized with, muscarinic receptors which were primarily distributed in the molecular layer of the lobules of the vestibulo-cerebellar lobules. Their functional significance is puzzling, since their distribution does not correspond to that of markers of cholinergic innervation.

Acetylcholinesterase↗

PubMed1995

Immunocytochemical localization of the heparin-binding growth-associated molecule (HB-GAM) in the developing and adult rat cerebellar cortex.

The heparin-binding, growth-associated molecule (HB-GAM) is a developmentally regulated protein that belongs to a new family of heparin-binding molecules, not related to the fibroblast growth factors (FGFs), with putative functions during cell growth and differentiation. In order to further study the functional role of HB-GAM we have used a polyclonal antiserum, raised against the purified protein to localize HB-GAM in the developing and adult rat cerebellar cortex. During postnatal development HB-GAM-like immunoreactivity (IR) was found to be present in all layers of the cerebellar cortex. IR was mainly associated with processes or extracellular structures but not with cell bodies. Throughout all the stages examined the molecular layer was clearly labeled, whereas staining in the internal granular layer was diffuse. IR in the external granular layer on postnatal day 1 and 8 was found to be associated with radially oriented fibres connecting the internal granular layer with the pial surface of the cerebellum. The intensity of this staining seemed to increase from day 1 to 8. Staining of corresponding areas with an antiserum against the glial fibrillary acidic protein (GFAP) suggested that the HB-GAM antiserum in the developing cerebellar cortex labels Bergmann glia fibres of Golgi epithelial cells. Because of the diffuse staining of the molecular layer in the adult rat it was not possible to distinguish whether radial fibres in the adult contained any HB-GAM IR. Golgi epithelial cells are considered as crucial for the migration of granular cells during the differentiation of the cerebellar cortex. We therefore speculate that the association of HB-GAM-like IR may be of functional relevance. The fact that molecules, such as tenascin, known to be involved in morphogenetic events show a similar spatiotemporal distribution pattern further underscores this hypothesis. HB-GAM, which possesses a classical signal sequence, might be release in the extracellular space and could mediate adhesion phenomena by binding to heparin-like molecules associated with the neuronal membrane. Therefore, it will be important to investigate whether specific antibodies against HB-GAM are able to interfere with normal cerebellar development in vitro and in vivo.

Animals↗

PubMed1986

Autoradiographic localization of ornithine decarboxylase in cerebellar cortex of the developing rat with [3H]alpha-difluoromethylornithine.

Ornithine decarboxylase was autoradiographically localized in the developing rat cerebellar cortex after intracisternal injection of [3H]alpha-difluoromethylornithine, a specific, irreversible inhibitor of the enzyme. At nine days of age, when cerebellar ornithine decarboxylase activity is maximal, autoradiographic grains were distributed over all layers of the cerebellar cortex and throughout the brain stem. Within cerebellar folia, the highest grain density was associated with the molecular layer, whereas the internal and external granule cell layers were less densely labeled. Enhancement of ornithine decarboxylase activity by intracisternally-administered isoproterenol correspondingly increased the autoradiographic grain density over each layer. Thus much of the polyamine biosynthetic capability needed to support neuronal and/or glial differentiation appears to be associated with the developing cell processes. The combination of [3H]alpha-difluoromethylornithine autoradiography with localized injection techniques provides a potentially powerful tool for the study of the involvement of polyamine biosynthesis in brain development.

Animals↗

PubMed1993

Optical imaging of parallel fiber activation in the rat cerebellar cortex: spatial effects of excitatory amino acids.

Using optical imaging, the effects of excitatory amino acids and their antagonists on the spatial pattern of activity evoked by the stimulation of parallel fibers in the cerebellar cortex of the anesthetized rat were examined. A vermal folium was stained with the stryrl voltage-sensitive dye RH-795 and imaged with a cooled charge-coupled service system during the activation of the parallel fibers with surface stimulation. Stimulation of the cerebellar cortex produced discrete "beams" of optical activity consistent with extracellular field recordings. The signal-to-noise ratio was excellent (> 10:1), reducing the number of stimuli, exposure time, and acquisition time needed to produce images. Extracellular field potential recordings were used to assay neuronal activity as well as the effects of the various excitatory amino acid agonists. Application of several glutamate receptor antagonists reversibly blocked the optical signals as well as the synaptic components of the extracellular field potentials. Neither N-methyl-D-aspartate nor its antagonist, (+/-)-2-amino-7-phosphonoheptanoic acid, had any affect on the optical signals or field potentials. These results indicate that the optical signal is not due to the evoked parallel fiber activity, but is generated mainly by postsynaptic targets and the parallel fiber synaptic action is primarily mediated by non-N-methyl-D-aspartate receptors. Other excitatory amino acid agonists had a differential effect on the optical response. Glutamate and kainate increased the "on beam" optical signal evoked by parallel fiber stimulation, in amplitude and width. In contrast, quisqualate always decreased the amplitude and width of the optical beam. Also, quisqualate produced an increase in fluorescence lateral to the optical beam, possibly due to an increase in "off beam" inhibitory activity. The changes in the extracellular field potentials were in agreement with the effects on the optical signals. Two possible mechanisms are proposed to account for the inhibitory effect of quisqualate. One is that quisqualate desensitizes Purkinje cell receptors, the other is that inhibitory interneurons in the cerebellar cortex are more preferentially excited with quisqualate application which in turn inhibits Purkinje cells both "on beam" and "off beam". In conclusion, voltage-sensitive dye optical signals evoked by stimulation of the cerebellar surface were imaged at high signal-to-noise levels using a cooled charge-coupled device system. Use of excitatory amino acid agonists and antagonists demonstrated that the optical signal was dependent on postsynaptic activity and confirmed that the parallel fiber postsynaptic action is primarily mediated by non-N-methyl-D-aspartate receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed2000

Serotonin-driven long-range inhibitory connections in the cerebellar cortex.

Disturbances of the serotoninergic neuromodulation in the cerebellar cortex have been involved in several types of ataxia, but the physiological action of serotonin in this structure remains poorly understood. We report that in slices of the rat cerebellar vermis, serotonin triggers the firing of an inhibitory interneuron presynaptic to Golgi cells. The Lugaro cell, a neglected interneuronal type, satisfies the expected criteria for this input, whereas basket cells, stellate cells, or Golgi cells do not. Lugaro cells are selectively excited by serotonin, and their firing behavior (sustained steady frequency in the 5-15 Hz range) resembles the pattern of occurrence of serotonin-evoked IPSCs in Golgi cells. Immunohistochemical stainings and single cell reconstructions show that Lugaro cell axons form a parasagittal plexus but also extend long transverse branches that run parallel to the parallel fibers and are partly myelinated. Electrophysiological data suggest that these transverse axons participate in synaptic contacts of the Lugaro cells with Golgi cells, and we calculated that in the intact cerebellum a given Lugaro cell contacts >100 Golgi cells. Serotonin modulation of Lugaro cells may constitute an intracortical switch involved in information patterning at the level of Golgi cells and granule cells populations, and particularly in synchronizations recorded along the transverse axis in vivo.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1975

Influence of morphine and naloxone on the release of noradrenaline from rat cerebellar cortex slices.

In slices of rat cerebellar cortex preincubated with (-)-3H-noradrenaline, the influence of morphine and naloxone on the efflux of tritium was investigated. The spontaneous outflow was not changed by 10(-5) M of either morphine or naloxone. On the other hand, morphine caused a concentration-dependent decrease of the overflow of tritium evoked by electrical field stimulation. Naloxone did not change the stimulation-induced overflow, but prevented its inhibition by morphine. It is concluded that morphine, through an action on opiate receptors located on cerebellar noradrenergic neurones, inhibits the secretion of the transmitter in response to nerve impulses.

Animals↗

PubMed2002

Ultrastructure of synaptic junctions in the cerebellar cortex in experimental valproate encephalopathy and after terminating chronic application of the antiepileptic.

The aim of the study was to analyse in TEM the evolution of changes in structural elements of synaptic junctions of the cerebellar cortex in rats in valproate encephalopathy induced by chronic 12-month administration of sodium valproate - VPA (once daily intragastrically, in a dose of 200 mg/kg b.w.) and after withdrawal of this antiepileptic for 1 and 3 months. After 9 and 12 months of the experiment, synaptic endings of both the symmetrical and asymmetrical synapses in the neuropil of the cerebellar cortex, especially in the molecular layer, showed signs of severe damage (mainly swelling) and even disintegration. They were mostly observed in axodendritic endings and axospinal endings on the dendritic spines of Purkinje cells, being manifested in the presence of large vacuolar structures, electron lucent areas and swollen mitochondria within the cytoplasm. A reduced number of axonal synaptic vesicles (with more type F vesicles preserved) could be seen. One and 3 months after the end of chronic application of VPA, the synaptic junctions did not show morphological exponents of the repair processes. The alterations observed in the synapticjunctions of the cerebellar cortex may suggest disorders in neurotransmission processes, such as exhaustion and damage caused by ischaemia due to damage to the blood-brain barrier induced by VPA and/or its toxic metabolites.

Animals↗

PubMed2000

PACAP acts as a neurotrophic factor during histogenesis of the rat cerebellar cortex.

During development of the rat cerebellum, PAC1 receptors are transiently expressed by neuroblasts of the external granule cell layer (EGL). We have previously shown that PACAP is a potent stimulator of granule cell survival in vitro. In the study reported in this paper, we have investigated the effect of PACAP on the development of the rat cerebellar cortex in vivo. PACAP induces a transient increase in the volume of the cerebellar cortex, with a maximum effect at postnatal day 12, which can be accounted for by an increase in the number of granule cells in the EGL, the molecular layer, and the internal granule cell layer (IGL). The effect of PACAP on the number of granule cells is blocked by the antagonist PACAP(6-38), which, by itself, produces a slight inhibition of the number of granule cells in the IGL. These data indicate that PACAP activates proliferation and/or inhibits programmed cell death of granule cells in the developing rat cerebellum. PACAP also stimulates neuronal migration from the EGL to the IGL. Thus, it appears that PACAP can act in vivo as a neurotrophic factor controlling histogenesis of the cerebellar cortex.

Animals↗

PubMed1988

Ontogenetic changes in laminar distribution of ornithine decarboxylase during development of cerebellar cortex: autoradiographic localization with [3H]alpha-difluoromethylornithine.

Ornithine decarboxylase is the first enzyme in the biosynthesis of the polyamines, which control macromolecule synthesis during cellular development. Polyamines appear to play a critical role in the development of the rat cerebellar cortex, since postnatal treatment with the specific irreversible ornithine decarboxylase inhibitor, alpha-difluoromethylornithine, arrests cell division and migration in this region. To determine whether the distribution of ornithine decarboxylase within the developing cerebellar cortex correlates with specific maturational events, [3H]alpha-difluoromethylornithine, a specific marker for ornithine decarboxylase activity, was localized autoradiographically in 3-13-day-old rats. The density of autoradiographic grains within the cerebellar cortex as a whole paralleled the postnatal rise and fall of biochemically determined ornithine decarboxylase activity. Superimposed on this pattern was a selective laminar distribution of label which indicated specific association of ornithine decarboxylase with cell replication, as shown by preferential labeling of the superficial (mitotic) zone of the external granule cell layer. In addition, ornithine decarboxylase activity was temporally associated with regions in which post-mitotic cells were undergoing migration, axonogenesis and dendritic arborization, as shown by the patterns obtained in deeper layers. In contrast, there was no evidence for an association between ornithine decarboxylase activity and synaptogenesis, gliogenesis or myelination. These results, in combination with previous biochemical and morphological data, support the view that the ornithine decarboxylase/polyamine system plays an important role in both mitotic and post-mitotic events within the nervous system.

Animals↗

PubMed1991

Development of cholinesterase histochemical staining in cerebellar cortex: transient expression of "nonspecific" cholinesterase in Purkinje cells of the nodulus and uvula.

Patterns of "nonspecific" cholinesterase (ChE) and acetylcholinesterase (AChE) activity were studied in developing rat cerebellar cortex by enzyme histochemistry and light and electron microscopy. Three types of ChE histochemical reaction product were observed in cerebellar cortex: (i) ChE is found in capillary endothelium throughout the cerebellum. Capillary ChE staining is present by the time of birth and continues into adulthood. (ii) ChE is found in radial glial fibers and their parent cell bodies, the Golgi epithelial cells. Radial glial fiber staining is mot intense during the first 3 weeks of postnatal life. (iii) ChE is found in Purkinje cells of the nodulus and ventral uvula. No ChE staining of Purkinje cells was seen in other parts of the cerebellum. ChE staining of Purkinje cells appears to be transient, first appearing at Postnatal Day 2 (P2), reaching peak intensity at P7-9, and decreasing to adult levels by P16. AChE activity displays a pattern markedly different from ChE, with staining in deep cerebellar nuclei, in putative mossy fiber terminals, and in Golgi neurons of cerebellar cortex. No evidence was found for transient AChE staining in Purkinje cells in any part of the cerebellum. The function of transiently expressed ChE activity in developing Purkinje neurons is unknown, but may be related to reorganization of cerebellar cortical circuitry associated with growth of mossy fiber afferents.

Acetylcholinesterase↗

PubMed1977

A computational model of cerebellar cortex and peripheral muscle.

A computational model, suitable for analytical or machine simulation studies, is developed for a specific cerebellar loop, the pathway from muscle fibre stretch receptors to the cerebellar cortex and back again. The model adheres to physiological data from the cat, and employs features from several existing models, including a single neuron model developed and tested earlier. Also included is a mechanical equivalent to an idealised muscle, in this case a rectangular array of muscle fibres which map 1-to-1 onto the array of compartments which form the cerebellar cortex. Much of the literature on cerebellar models is briefly reviewed, as are several key physiological experiments.

Animals↗

PubMed1986

Cellular localization of proenkephalin mRNA in rat brain: gene expression in the caudate-putamen and cerebellar cortex.

The cellular locations of proenkephalin mRNA have been determined for the caudate-putamen and cerebellar cortex of the rat brain by in situ hybridization. In the caudate-putamen, more than half of the neurons express the proenkephalin gene. Morphologically, they are medium-sized cells that may represent projection neurons. In the cerebellar cortex, proenkephalin mRNA is present in a subpopulation of neurons in the granule layer that appear to be Golgi cells--i.e., inhibitory interneurons. The presence of [Met]enkephalin, a pentapeptide derived from proenkephalin, in these two brain areas is consistent with a synthetic role for this mRNA and implicates proenkephalin gene expression in the control of motor function.

Animals↗

PubMed2005

In vivo calcium imaging of circuit activity in cerebellar cortex.

In vivo two-photon calcium imaging provides the opportunity to monitor activity in multiple components of neural circuitry at once. Here we report the use of bulk-loading of fluorescent calcium indicators to record from axons, dendrites, and neuronal cell bodies in cerebellar cortex in vivo. In cerebellar folium crus IIa of anesthetized rats, we imaged the labeled molecular layer and identified all major cellular structures: Purkinje cells, interneurons, parallel fibers, and Bergmann glia. Using extracellular stimuli we evoked calcium transients corresponding to parallel fiber beam activity. This beam activity triggered prolonged calcium transients in interneurons, consistent with in vitro evidence for synaptic activation of N-methyl-d-aspartate receptors via glutamate spillover. We also observed spontaneous calcium transients in Purkinje cell dendrites that were identified as climbing-fiber-evoked calcium spikes by their size, time course, and sensitivity to AMPA receptor antagonist. Two-photon calcium imaging of bulk-loaded cerebellar cortex is thus well suited to optically monitor synaptic processing in the intact cerebellum.

Animals↗

PubMed2001

Role of calcium, glutamate neurotransmission, and nitric oxide in spreading acidification and depression in the cerebellar cortex.

This study investigated the mechanisms underlying the recently reported fast spreading acidification and transient depression in the cerebellar cortex in vivo. Spreading acidification was evoked by surface stimulation in the rat and mouse cerebellar cortex stained with the pH-sensitive dye neutral red and monitored using epifluorescent imaging. The probability of evoking spreading acidification was dependent on stimulation parameters; greater frequency and/or greater amplitude were more effective. Although activation of the parallel fibers defined the geometry of the spread, their activation alone was not sufficient, because blocking synaptic transmission with low Ca(2+) prevented spreading acidification. Increased postsynaptic excitability was also a major factor. Application of either AMPA or metabotropic glutamate receptor antagonists reduced the likelihood of evoking spreading acidification, but stronger stimulation intensities were still effective. Conversely, superfusion with GABA receptor antagonists decreased the threshold for evoking spreading acidification. Blocking nitric oxide synthase (NOS) increased the threshold for spreading acidification, and nitric oxide donors lowered the threshold. However, spreading acidification could be evoked in neuronal NOS-deficient mice (B6;129S-Nos1(tm1plh)). The depression in cortical excitability that accompanies spreading acidification occurred in the presence of AMPA and metabotropic glutamate receptor antagonists and NOS inhibitors. These findings suggest that spreading acidification is dependent on extracellular Ca(2+) and glutamate neurotransmission with a contribution from both AMPA and metabotropic glutamate receptors and is modulated by nitric oxide. Therefore, spreading acidification involves both presynaptic and postsynaptic mechanisms. We hypothesize that a regenerative process, i.e., a nonpassive process, is operative that uses the cortical architecture to account for the high speed of propagation.

Acids↗