Properties of the slow excitatory postsynaptic potential in mammalian sympathetic ganglia neurons

Slow EPSPs evoked in the neurons of the rabbit isolated superior cervical ganglion were studied using intracellular microelectrodes. Two types of EPSPs occurring in different neurons were found. The type I slow EPSPs showed an increase during hyperpolarization of the membrane and a decrease during its depolarization. Input resistance of the neurons during the response either decreased or remained unchanged. The type II slow EPSPs were increased by depolarization and decreased by hyperpolarization with the reversal potential -78.9 +/- 3.6 mV. Depolarization evoked by acetylcholine or carbocholine was followed by an increase in the input resistance in 53% of neurons with reversal potential -83.2 +/- 6.7 mV. It is concluded that in the first group of the neurons the nature of the slow EPSP is similar to that of ordinary EPSP. The main component underlying the ionic mechanism of slow EPSP in the other group of the neurons is a decrease in potassium conductance of the membrane.     

Modulation of action potential during the late slow excitatory postsynaptic potential in bullfrog sympathetic ganglia

The spike peak and after-hyperpolarization of the action potential of bullfrog sympathetic ganglion cells were depressed during the late slow excitatory postsynaptic potential (EPSP). These changes in the action potential were mimicked by luteinizing hormone-releasing hormone (LH-RH), a neurotransmitter candidate for the late show EPSP. LH-RH (5 μM) suppressed the voltage-dependent K⁺ currents, both the delayed rectifier K⁺ current (I_K1) and the M current (I_K2). It is suggested that the depression of the after-hyperpolarization of the action potential during the late slow EPSP may be due to suppression of I_K1 and I_K2.     

Multiple conductance change associated with the slow excitatory potential in mammalian sympathetic neurons

When the membrane potential was manually clamped, the non-cholinergic excitatory potential was associated with either a sustained increase, an initial decrease followed by a prolonged increase or no apparent change in neuronal input resistance. In the majority of neurons studied, the amplitude of non-cholinergic depolarization was augmented upon conditioning hyperpolarization, whereas it was attenuated in a low Na solution. The results are consistent with the suggestion that the non-cholinergic depolarization may be generated by a change of multiple conductances that may include G_Na activation and G_K inactivation.     

Evidence of slow IPSP in mammalian prevertebral ganglia

A short train of nerve stimulation evoked in a portion of neurons of the guinea pig inferior mesenteric ganglia a slow hyperpolarization (slow IPSP) which persisted when the preceding orthodromic spikes were reduced to subthreshold EPSPs by curare, was reversibly abolished in a low Ca solution, and was not blocked by atropine; furthermore, the post-tetanic hyperpolarization induced by direct intracellular stimulation was generally smaller than the slow IPSP evoked by nerve stimulation. The slow IPSP was often associated with a fall in membrane resistance and its amplitude decreased with membrane hyperpolarization. The results indicate that the slow hyperpolarization is a synaptic potential, and differs from the slow IPSP observed in mammalian and amphibian paravertebral ganglionic neurons in that it is atropine insensitive.     

Vasopressin-mediated slow EPSPs in a mammalian sympathetic ganglion

Vasopressin is one of numerous neuropeptides contained in sympathetic ganglia, but whose function remains unresolved. In this report, we present electrophysiological evidence that arginine-vasopressin (AVP) is a neurotransmitter in guinea pig inferior mesenteric ganglion (IMG). AVP superfused over the IMG, in vitro, produced in a population of neurons a membrane depolarization accompanied by a resistance increase, both of which were blocked by a specific V1 receptor antagonist. Moreover, slow excitatory postsynaptic potentials (EPSPs) elicited by repetitive nerve stimulation were attenuated in 75% of cells tested in the presence of excess AVP, and occasionally in the presence of the antagonist. Thus, AVP joins substance P as a putative transmitter of slow potentials in the guinea pig IMG.     

Cholinergic excitatory synaptic potentials of neurones in mammalian lumbar paravertebral ganglia

Synaptic potentials and the electrophysiological properties of 201 cells in the 4th lumbar paravertebral ganglia of the rabbit were studied in vitro using intracellular electrophysiological recording techniques. Cells had a mean transmembrane potential of 55.1 +/- 0.8 mV, a mean input resistance of 37.0 +/- 6.6 M omega (range 29.9-61.1) and a mean membrane time constant of 6.0 +/- 0.6 ms. Synaptic potentials in ganglionic neurones were evoked by electrical stimulation of the rami communicantes, inferior lumbar splanchnic nerves and the paravertebral chain from segments both above and below the L4 ganglion. Synaptic responses consisted of a fast, hexamethonium-sensitive component and, following short periods of higher frequency stimulation, a slow, long lasting, pirenzepine and atropine-sensitive depolarization (slow-EPSP). No phenomenon corresponding to a late slow-EPSP was observed and, under our recording conditions no cells exhibited non-cholinergic slow excitatory or slow inhibitory postsynaptic potentials. It is concluded that fast excitatory synaptic events were mediated by nicotinic receptors whereas slow excitatory synaptic events were mediated by muscarinic m1 receptors. McNeil-A-343, a muscarinic agonist, produced membrane depolarization, a decrease in membrane input conductance and in some cells a repetitive discharge of action potentials. In 60% of cells tested substance P produced a depolarization of the membrane potential with an associated decrease in membrane input conductance.     

The basal ganglia network mediates the planning of movement amplitude

This study addresses the hypothesis that the basal ganglia (BG) are involved specifically in the planning of movement amplitude (or covariates). Although often advanced, based on observations that Parkinson's disease (PD) patients exhibit hypokinesia in the absence of significant directional errors, this hypothesis has been challenged by a recent alternative, that parkinsonian hypometria could be caused by dysfunction of on-line feedback loops. To re-evaluate this issue, we conducted two successive experiments. In the first experiment we assumed that if BG are involved in extent planning then PD patients (who exhibit a major dysfunction within the BG network) should exhibit a preserved ability to use a direction precue with respect to normals, but an impaired ability to use an amplitude precue. Results were compatible with this prediction. Because this evidence did not prove conclusively that the BG is involved in amplitude planning (functional deficits are not restricted to the BG network in PD), a second experiment was conducted using positron emission tomography (PET). We hypothesized that if the BG is important for planning movement amplitude, a task requiring increased amplitude planning should produce increased activation in the BG network. In agreement with this prediction, we observed enhanced activation of BG structures under a precue condition that emphasized extent planning in comparison with conditions that emphasized direction planning or no planning. Considered together, our results are consistent with the idea that BG is directly involved in the planning of movement amplitude or of factors that covary with that parameter.     

Tachykinins produce fast and slow depolarizations in sympathetic neurons of rat coeliac-superior mesenteric ganglia

The actions of mammalian tachykinins on neurons of rat coeliac-superior mesenteric ganglia (C-SMG) were examined using intracellular recording in isolated preparations. Application of substance P, neurokinin A and neurokinin B produced fast and slow depolarizations in the ganglion cells. The two responses were clearly distinguishable in their electrophysiological characteristics. The results suggest that different receptor mechanisms are involved in fast and slow depolarizing actions of tachykinins in rat C-SMG cells.     

Serotonin as a neurotransmitter in cerebral arteries

Evidence is presented for the existence of serotoninergic nerves in rabbit verterbral artery: the neurogenic vasoconstrictor response in isolated vessels was resistant to adrenoceptor and cholinoceptor blockede but was blocked by ketanserin, a serotonin (5-HT) antagonist; vertebral arteries contained high levels of 5-HT (over 0.5 μg/g wet weight) and its metabolite, 5-hydroxyindoleacetic acid (over 0.6 μg/g wet weight); and a 5-HT-immunoreactive nerve plexus was demonstrated. The possible role of these nerves is discussed.     

Oestradiol Modulation of Serotonin Reuptake Transporter and Serotonin Metabolism in the Brain of Monkeys

Serotonin (5-hydroxytryptamine; 5-HT) is an important brain neurotransmitter that is implicated in mental and neurodegenerative diseases and is modulated by ovarian hormones. Nevertheless, the effect of oestrogens on 5-HT neurotransmission in the primate caudate nucleus, putamen and nucleus accumbens, which are major components of the basal ganglia, and the anterior cerebral cortex, mainly the frontal and cingulate gyrus, is not well documented. The present study evaluated 5-HT reuptake transporter (SERT) and 5-HT metabolism in these brain regions in response to 1-month treatment with 17β-oestradiol in short-term (1 month) ovariectomised (OVX) monkeys (Macaca fascicularis). SERT-specific binding was measured by autoradiography using the radioligand [³H]citalopram. Biogenic amine concentrations were quantified by high-performance liquid chromatography. 17β-Oestradiol increased SERT in the superior frontal cortex and in the anterior cingulate cortex, in the nucleus accumbens, and in subregions of the caudate nucleus of OVX monkeys. 17β-Oestradiol left [³H]citalopram-specific binding unchanged in the putamen, as well as the dorsal and medial raphe nucleus. 17β-Oestradiol treatment decreased striatal concentrations of the precursor of 5-HT, 5-hydroxytryptophan, and increased 5-HT, dopamine and 3-methoxytyramine concentrations in the nucleus accumbens, caudate nucleus and putamen, whereas the concentrations of the metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid and homovanillic acid remained unchanged. No effect of 17β-oestradiol treatment was observed for biogenic amine concentrations in the cortical regions. A significant positive correlation was observed between [³H]citalopram-specific binding and 5-HT concentrations in the caudate nucleus, putamen and nucleus accumbens, suggesting their link. These results have translational value for women with low oestrogen, such as those in surgical menopause or perimenopause.     

Evoked slow muscarinic acetylcholinergic synaptic potentials in rat hippocampal interneurons

The hippocampus receives an extensive cholinergic input from the medial septal nucleus that ramifies throughout all layers and plays a pivotal modulatory role in cognitive function. Although the pharmacological effects of exogenous application of cholinergic agonists have been extensively studied in hippocampal neurons, much less is known about the effects of synaptically released acetylcholine (ACh). In this respect, most studies have focused on the cholinergic afferent input to pyramidal neurons that produces a characteristically slow depolarizing synaptic response mediated by activation of muscarinic ACh receptors (mAChRs). Here we report that cholinergic afferent stimulation also elicits atropine-sensitive synaptic potentials in hippocampal CA1 interneurons but, in contrast to synaptic responses in pyramidal neurons, these are highly diverse in waveform, although can still be classified into five distinct subtypes. The most common response type (i) 64% of cells) consisted of a slow sustained membrane potential depolarization. The other 36% of responses could be subdivided into responses comprising of (ii) a biphasic membrane potential change in which an initial slow hyperpolarization subsequently transforms into a slow depolarization (20%), (iii) a pure, slow hyperpolarization (13%), and (iv) an oscillatory response persisting for several seconds (2%). Interestingly, there were also interneurons totally insensitive to both synaptic and pharmacological cholinergic challenge. Morphological investigation of recorded cells revealed no obvious correlation between responsiveness to cholinergic afferent stimulation and dendritic and axonal arborization. The current study suggests that synaptic release of ACh results in a complex and differential mAChR-mediated modulation of cellular excitability within the hippocampal interneuron population.     

Restless legs syndrome is a common feature of adult celiac disease

Restless legs syndrome (RLS) is a common neurological condition, frequently idiopathic, sometimes associated with specific disorders such as iron deficiency. We investigated RLS prevalence in celiac disease (CD), an autoimmune disease characterized by several features such as malabsorption‐related iron deficiency anemia and peripheral neuropathy. We screened a population of 100 adult CD patients for CD features, iron metabolism, clinical and neurological conditions, and enrolled 100 age‐ and sex‐matched controls in the general population. RLS was ascertained in CD patients and controls by both the presence of the four essential International RLS Study Group diagnostic criteria and neurological examination. The International RLS Study Group rating scale was used to measure RLS severity. We found a 31% prevalence of RLS in the CD population that was significantly higher than the prevalence in the control population (4%; P < 0.001). The average severity of RLS in CD population was moderate (17 ± 6.5). In the CD population, no significant correlation was found between RLS and either gluten‐free diet or iron metabolism, despite hemoglobin levels were significantly lower in CD patients with RLS than without RLS (P = 0.003). We found no correlation between RLS and other possible causes of secondary RLS, including signs of peripheral neuropathy, pregnancy, end‐stage renal disease, and pharmacological treatments.Our study broadens the spectrum of neurological disorders associated with CD and indicates that RLS should be sought for in all patients with CD. © 2010 Movement Disorder Society     

Neurofilament immunoreactivity in developing rat autonomic and sensory ganglia

Immunoreactivity to neurofilament (NF) antiserum appears early in the development of both the central and peripheral nervous systems of the rat fetus. In 10 somite embryos, positive cell bodies are present in the ventromedial part of anterior rhombencephalic and mesencephalic neural tube. From there the appearance of immunoreactivity spreads cranially to the prosencephalic anlage before closure of the anterior neuropore and caudally following the sequence of neural tube closure. Immunoreactivity increases rapidly in axon bundles of central and peripheral systems, but in immature cell bodies of sensory ganglia the NF material only forms a ring around the nucleus. At 16 days of gestation, some cell bodies are progressively loaded with NF-immunoreactive material as a thick perinuclear network first and then in more excentrically located aggregates. This category of neurons is mainly observed in the distal part of the trigeminal ganglion, in petrous and nodose ganglia and in cervical dorsal root ganglia. In adult ganglia large cell bodies and some small ones present high NF immunoreactivity. In autonomic cell bodies (in superior cervical ganglion and in parasympathetic cranial ganglia) the immunoreactive material only forms a perinuclear ring slowly transformed into a loose perinuciear meshwork at the end of gestation. Intensely reactive nerve fibers are observed in cranial sensory as well as in sympathetic and parasympathetic ganglia and nerves. No positive cell bodies and only a few NF-immunoreactive nerves are observed in the carotid bodies. The NF immunoreactivity is better visualized on sections of fresh frozen material, treated with acetone, than in fixed specimens.These results are compared to previous observations reported for other species and for developing dorsal root ganglia. This immunostaining may be used to detect differentiation of peripheral sensory and autonomic neurons under experimental conditions. The uneven distribution of NF immunoreactivity in sensory neurons from stage 16 days of gestation as specific for precise subpopulations of neurons is discussed.     

Long-term effects of striatal lesions on c-Fos immunoreactivity in the pedunculopontine nucleus

The basal ganglia are a group of subcortical nuclei classically thought to be involved in the control of movement, and they have reciprocal connections with the cortex, thalamus and structures in the brainstem. Recent findings suggest that the basal ganglia interact with structures involved in the control of the sleep-waking cycle. The pedunculopontine tegmental nucleus (PPN) maintains a close relationship with the basal ganglia and is intimately involved in the regulation of wakefulness and REM sleep. This study evaluated changes in activity of PPN neurons following striatal kainic acid-induced lesions. Rats were injected in the anterodorsal striatum with either kainic acid or vehicle and allowed to recover for 7 or 30 days. The results showed an increase in the number of c-Fos+ cells in the PPN 30 days but not 7 days after the striatal lesion, when motor hyperactivity was no longer detected. In addition, we found a significant correlation between the ventricular brain ratio, as an indicator of lesion size, and the number of c-Fos+ cells in the PPN. Furthermore, the spatial distribution of cell types suggested that most c-Fos+ cells in the PPN were not cholinergic. These results provide new insights into the functional relationship between the basal ganglia and the PPN and suggest that the striatum, through its indirect influence on the PPN, may contribute to the regulation of wakefulness and cortical activation.     

Neurological disorders in 166 patients with basal ganglia calcification: a statistical evaluation

Summary Patients investigated at our institute during the last decade included 166 (1.2%) who showed uni- orbilateral basal ganglia calcification on computed tomography. We tested the significance of this neuroradiological observation by statistical comparison of these patients' clinical disorders with the findings in a random sample of 622 patients without basal ganglia calcification. The odds for the most common neurological disturbances were similar in patients with and without basal ganglia calcification. After adjustment for differences in age and brain atrophy there was no evidence of a significantly increased risk of dementia (odds ratio 1.1), cerebral infarction (1.4), epilepsy (0.9), vertigo (1.6), headache (1.8), or alcoholism (0.9), which represented the most common diagnoses. We conclude that basal ganglia calcification cannot be considered as a clinically relevant neuroradiological finding in the majority of cases and that it should not be used as an explanation for frequently observed neurological disturbances.     

Exogenous silver in dorsal root ganglia,peripheral nerve,enteric ganglia,and adrenal medulla

Summary Following intraperitoneal (i.p.) or oral administration of silver salts, the anatomic distribution of silver in the peripheral nervous system (PNS) has been studied. The structures examined were dorsal root ganglia, peripheral nerve (N. ischiadicus), enteric ganglia, and adrenal medulla.Four days after an i.p. injection of silver lactate, silver deposits were found in these structures. The silver content remained stable during the observation period (45 days).The localization of silver deposits in the orally treated animals was independent of the administered silver salt (silver nitrate or silver lactate).The silver deposits in neurons and chromaffin cells were located in the cytoplasm. In all organs silver was present in large amounts in connective tissue membranes, macrophage-like cells, vascular basal laminae, and supporting cells. Satellite cells of the dorsal root ganglia were always heavily stained, white less stain was present in Schwann cells of the peripheral nerves.Intracellular deposits were invariably located in lysosomes, whereas extracellular grains were found in connective tissue fibers and basement membranes.     

Macro-aneurysm in the basal ganglia region

A 59-year-old female patient suddenly developed vomiting and gait disturbances followed by decreasing consciousness. CT scans revealed a hemorrhage within the left basal ganglia region with rupture into the ventricles and consecutive hydrocephalus. On angiography an aneurysm in the region of the caput nuclei caudati was shown to be the source of the bleeding. On repeat-angiography 4 months later the aneurysm was no longer visualized, probably due to thrombosis. This is an extraordinary case of a basal ganglia aneurysm comparable with the aneurysms of Willis' circle, but located in a region where generally microaneurysms — mostly combined with hypertension or moyamoya disease can be found.     

Event-related potential activity in the basal ganglia differentiates rewards from nonrewards: response to commentary

We recently demonstrated that the feedback negativity may be better understood as a reward-related positivity that is absent on nonreward trials, and source localization revealed that this reward response may reflect activity in the striatum. In a commentary on our report, Cohen et al. argue against this latter finding, claiming it is unlikely that the striatum contributes to the scalp-recorded event-related potential. We disagree with the line of reasoning presented by Cohen et al., and we respond here to each of their points. Based on all the available evidence, we argue that the striatum is a plausible generator of a reward-related response observed at the scalp, and this possibility warrants further investigation.     

Neurological symptoms in patients with biopsy proven celiac disease

In celiac disease (CD), the gut is the typical manifestation site but atypical neurological presentations are thought to occur in 6 to 10% with cerebellar ataxia being the most frequent symptom. Most studies in this field are focused on patients under primary neurological care. To exclude such an observation bias, patients with biopsy proven celiac disease were screened for neurological disease. A total of 72 patients with biopsy proven celiac disease (CD) (mean age 51 ± 15 years, mean disease duration 8 ± 11 years) were recruited through advertisements. All participants adhered to a gluten‐free diet. Patients were interviewed following a standard questionnaire and examined clinically for neurological symptoms. Medical history revealed neurological disorders such as migraine (28%), carpal tunnel syndrome (20%), vestibular dysfunction (8%), seizures (6%), and myelitis (3%). Interestingly, 35% of patients with CD reported of a history of psychiatric disease including depression, personality changes, or even psychosis. Physical examination yielded stance and gait problems in about one third of patients that could be attributed to afferent ataxia in 26%, vestibular dysfunction in 6%, and cerebellar ataxia in 6%. Other motor features such as basal ganglia symptoms, pyramidal tract signs, tics, and myoclonus were infrequent. 35% of patients with CD showed deep sensory loss and reduced ankle reflexes in 14%. Gait disturbances in CD do not only result from cerebellar ataxia but also from proprioceptive or vestibular impairment. Neurological problems may even develop despite strict adherence to a gluten‐free diet. © 2009 Movement Disorder Society