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The Journal of Physiology Mar 2005Whole-cell patch recordings were made from parasympathetic preganglionic neurones (P-PGNs) and unidentified intermediolateral (IML) neurones in thick slices of the lower...
Whole-cell patch recordings were made from parasympathetic preganglionic neurones (P-PGNs) and unidentified intermediolateral (IML) neurones in thick slices of the lower lumbar and sacral spinal cord of 14- to 21-day-old rats. The P-PGNs and IML neurones examined were similar in terms of soma sizes, input resistance and capacitance, and displayed a sag conductance as well as rebound firing. In the absence of drugs, the neurones responded with either tonic or adapting firing to depolarizing current steps. However, in the presence of the group I metabotropic glutamate receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG), almost half of the neurones displayed accelerating firing rates during the constant current injection, followed by a sustained after-discharge. In the presence of TTX, plateau potentials were observed. The firing changes and plateaux were blocked by nifedipine, an L-type Ca2+ channel blocker, and (S)-(-)-Bay K8644 was able to produce these firing changes and plateaux in the absence of DHPG, demonstrating the involvement of an L-type Ca2+ conductance. Ca2+-activated nonspecific cationic conductances also appear to contribute to the firing changes. A few neurones displayed membrane oscillations and burst firing in the presence of DHPG. The results suggest that the firing characteristics of both P-PGNs and other neurones likely to be involved in caudal spinal reflex control are not static but, rather, quite dynamic and under metabotropic glutamate receptor modulatory control. Such changes in firing patterns may be involved in normal pelvic parasympathetic reflex function during micturition, defaecation and sexual reflexes, and may contribute to the abnormal output patterns seen with loss of descending brainstem input and visceral or perineal sensory disturbances.
Topics: Animals; Autonomic Fibers, Preganglionic; Calcium Channels; Female; Ganglia, Parasympathetic; Male; Membrane Potentials; Neurons; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate; Spinal Cord
PubMed: 15618277
DOI: 10.1113/jphysiol.2004.076802 -
ENeuro Apr 2024Neuromodulation of the peripheral nervous system (PNS) by electrical stimulation may augment autonomic function after injury or in neurodegenerative disorders. Nerve...
Neuromodulation of the peripheral nervous system (PNS) by electrical stimulation may augment autonomic function after injury or in neurodegenerative disorders. Nerve fiber size, myelination, and distance between individual fibers and the stimulation electrode may influence response thresholds to electrical stimulation. However, information on the spatial distribution of nerve fibers within the PNS is sparse. We developed a new two-dimensional (2D) morphological mapping tool to assess spatial heterogeneity and clustering of nerve fibers. The L6-S3 ventral roots (VRs) in rhesus macaques were used as a model system to map preganglionic parasympathetic, γ-motor, and α-motor fibers. Random and ground truth distributions of nerve fiber centroids were determined for each VR by light microscopy. The proposed tool allows for nonbinary determinations of fiber heterogeneity by defining the minimum distance between nerve fibers for cluster inclusion and comparisons with random fiber distributions for each VR. There was extensive variability in the relative composition of nerve fiber types and degree of 2D fiber heterogeneity between different L6-S3 VR levels within and across different animals. There was a positive correlation between the proportion of autonomic fibers and the degree of nerve fiber clustering. Nerve fiber cluster heterogeneity between VRs may contribute to varied functional outcomes from neuromodulation.
Topics: Animals; Macaca mulatta; Spinal Nerve Roots; Autonomic Pathways; Cluster Analysis
PubMed: 38548331
DOI: 10.1523/ENEURO.0009-23.2024 -
Journal of Neurophysiology Dec 2021Barrington's nucleus (Bar), which controls micturition behavior through downstream projections to the spinal cord, contains two types of projection neurons, Bar and Bar,...
Barrington's nucleus (Bar), which controls micturition behavior through downstream projections to the spinal cord, contains two types of projection neurons, Bar and Bar, that have different functions and target different spinal circuitry. Both types of neurons project to the L-S spinal intermediolateral (IML) nucleus, whereas Bar neurons also project to the dorsal commissural nucleus (DCN). To obtain more information about the spinal circuits targeted by Bar, we used patch-clamp recording in spinal slices from adult mice in combination with optogenetic stimulation of Bar terminals. Recording of opto-evoked excitatory postsynaptic currents (oEPSCs) in 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine, 4-chlorobenzenesulfonate (DiI)-labeled lumbosacral preganglionic neurons (LS-PGNs) revealed that both Bar neuronal populations make strong glutamatergic monosynaptic connections with LS-PGNs, whereas Bar neurons also elicited smaller-amplitude glutamatergic polysynaptic oEPSCs or polysynaptic opto-evoked inhibitory postsynaptic currents (oIPSCs) in some LS-PGNs. Optical stimulation of Bar and Bar terminals also elicited monosynaptic oEPSCs and polysynaptic oIPSCs in sacral DCN neurons, some of which must include interneurons projecting to either the IML or ventral horn. Application of capsaicin increased opto-evoked firing during repetitive stimulation of Bar terminals through the modulation of spontaneous postsynaptic currents in LS-PGNs. In conclusion, our experiments have provided insights into the synaptic mechanisms underlying the integration of inputs from Bar to autonomic circuitry in the lumbosacral spinal cord that may control micturition. Photostimulation of Bar or Bar axons in the adult mouse spinal cord elicits excitatory or inhibitory postsynaptic responses in multiple cell types related to the autonomic nervous system including preganglionic neurons (PGNs) in the lumbosacral intermediolateral nucleus and interneurons in the lumbosacral dorsal commissure nucleus. Integration of excitatory inputs from Bar and from visceral primary afferents in PGNs may be important in the regulation of micturition behavior.
Topics: Animals; Autonomic Fibers, Preganglionic; Autonomic Nervous System; Barrington's Nucleus; Electrophysiological Phenomena; Excitatory Postsynaptic Potentials; Female; Male; Mice; Optogenetics; Patch-Clamp Techniques; Spinal Cord
PubMed: 34731061
DOI: 10.1152/jn.00026.2021 -
Acta Neurobiologiae Experimentalis 1996The activity of preganglionic sympathetic neurones largely depends on synaptic excitation from antecedent reticulospinal neurones located in the rostral ventrolateral... (Review)
Review
The activity of preganglionic sympathetic neurones largely depends on synaptic excitation from antecedent reticulospinal neurones located in the rostral ventrolateral medulla (RVLM). Our study, conducted in anaesthetized rats, showed that all RVLM pre-sympathetic neurones display a substantial synaptic noise and their action potentials are usually preceded by fast EPSPs. No evidence was found for presence of gradual depolarizations (autodepolarizations) between individual spikes. Therefore our results are consistent with the "network" hypothesis for the generation of sympathetic vasomotor tone. Axons of some pre-sympathetic neurones intracellularly labelled with Neurobiotin or Lucifer Yellow had collaterals arborizing in several medullary regions. Thus these neurones have synaptic inputs not only to preganglionic sympathetic neurones, but also to other, yet unidentified cells in the brainstem. Finally, our results show that anatomically adjacent RVLM pre-sympathetic and Bötzinger respiratory neurones from two functionally distinct neuronal subpopulations, and that some pre-sympathetic neurones have an adrenergic phenotype.
Topics: Animals; Autonomic Fibers, Preganglionic; Electrophysiology; Medulla Oblongata; Neurons; Rats; Sympathetic Nervous System
PubMed: 8787198
DOI: 10.55782/ane-1996-1141 -
Frontiers in Cellular Neuroscience 2017Functional properties of lamina X neurons in the spinal cord remain unknown despite the established role of this area for somatosensory integration, visceral...
Functional properties of lamina X neurons in the spinal cord remain unknown despite the established role of this area for somatosensory integration, visceral nociception, autonomic regulation and motoneuron output modulation. Investigations of neuronal functioning in the lamina X have been hampered by technical challenges. Here we introduce an spinal cord preparation with both dorsal and ventral roots still attached for functional studies of the lamina X neurons and their connectivity using an oblique LED illumination for resolved visualization of lamina X neurons in a thick tissue. With the elaborated approach, we demonstrate electrophysiological characteristics of lamina X neurons by their membrane properties, firing pattern discharge and fiber innervation (either afferent or efferent). The tissue preparation has been also probed using Ca imaging with fluorescent Ca dyes (membrane-impermeable or -permeable) to demonstrate the depolarization-induced changes in intracellular calcium concentration in lamina X neurons. Finally, we performed visualization of subpopulations of lamina X neurons stained by retrograde labeling with aminostilbamidine dye to identify sympathetic preganglionic and projection neurons in the lamina X. Thus, the elaborated approach provides a reliable tool for investigation of functional properties and connectivity in specific neuronal subpopulations, boosting research of lamina X of the spinal cord.
PubMed: 29163053
DOI: 10.3389/fncel.2017.00342 -
Journal of Clinical Medicine Nov 2021Spinocerebellar ataxia type 1 (SCA-ATXN1) is an autosomal dominant, neurodegenerative disease, caused by CAG repeat expansion in the ataxin-1 gene (). In isolated...
Spinocerebellar ataxia type 1 (SCA-ATXN1) is an autosomal dominant, neurodegenerative disease, caused by CAG repeat expansion in the ataxin-1 gene (). In isolated reports of patients with neurological signs [symptomatic patients (SP)], macular abnormalities have been described. However, no reports exist about macular anomalies in SCA1 subjects carrying the mutation without neurological signs [not symptomatic carriers (NSC)]. Therefore, the main aim of our work was to evaluate whether the macular functional and morphological abnormalities could be detectable in SP, genetically confirmed and with neurological signs, as well as in SCA-ATXN1-NSC, harboring pathogenic CAG expansion in In addition, we investigated whether the macular involvement could be associated or not to an impairment of RGCs and of their fibers and of the neural conduction along the visual pathways. Herein, nine SCA-ATXN1 subjects (6 SP and 3 NSC) underwent the following examinations: visual acuity and chromatic test assessments, fundus oculi (FO) examination, macular and peripapillary retinal nerve fiber layer thickness (RNFL-T) analysis by Spectral domain-Optical Coherence Tomography (Sd-OCT) acquisition, multifocal electroretinogram (mfERG), pattern reversal electroretinogram (PERG) and visual evoked potentials (VEP) recordings. In four eyes of two SP, visual acuity reduction and chromatic abnormalities were observed; in three of them FO changes associated with macular thinning and outer retinal defects were also detected. In three NSC eyes, slight FO abnormalities were associated with qualitative macular morphological changes. By contrast, abnormal mfERG responses (exclusively from foveal and parafoveal areas) were detected in all SP and NSC (18 eyes). No abnormalities of PERG values, RNFL-T, and VEP responses were found, but in one SP, presenting abnormal papillo-macular bundle neural conduction. Results from our SCA-ATXN1 cohort suggest that a macular dysfunction, detectable by mfERG recordings, may occur in the overt disorder, and unexpectedly in the stage of the disease in which there is still an absence of neurological signs. In NSC, an exclusive dysfunction of preganglionic macular elements can be observed, and this is associated with both normal RGCs function and neural conduction along the visual pathways.
PubMed: 34830553
DOI: 10.3390/jcm10225271 -
Brain Research Bulletin 1994After complete cat spinal cord transection, a collagen matrix was used to bridge the gap. Vascular supply was increased to the transection site with an omental pedicle.... (Review)
Review
After complete cat spinal cord transection, a collagen matrix was used to bridge the gap. Vascular supply was increased to the transection site with an omental pedicle. Before hardening, either 4-aminopyridine, laminin, glia maturation factor, or lipid angiogenic factor were mixed into the collagen. Surgically reconstructed animals were compared to transection-only controls and observed for 90 days. Fluoro-Gold was injected distal to the transection site on day 75. Immunocytochemical examination of brain and spinal cord tissue was done on day 90. Examination revealed supraspinal catecholaminergic fibers present in the collagen bridge and distal cord tissue only in cats with surgical reconstruction. Fluoro-Gold particles were found localized in locus coeruleus and other noradrenergic pontine neurons. Distal to the transection, double immunostaining with synaptophysin and tyrosine hydroxylase or dopamine-beta-hydroxylase revealed dot-like deposits closely apposed to preganglionic sympathetic neurons suggestive of synaptic connectivity to these targets. Results indicate that considerable outgrowth of specific supraspinal fibers can be induced following spinal transection and reconstruction, and that such fibers may be extending and contacting appropriate distal target tissue in the cord.
Topics: Animals; Cats; Female; Locus Coeruleus; Nerve Fibers; Nerve Regeneration; Spinal Cord; Spinal Cord Injuries
PubMed: 7859097
DOI: 10.1016/0361-9230(94)90153-8 -
The Journal of Comparative Neurology Mar 2008Urocortin is a novel neurotransmitter that appears to play a role in eating and drinking behavior. Most urocortin-positive (urocortin(+)) neurons in rodents are found in... (Comparative Study)
Comparative Study
Urocortin is a novel neurotransmitter that appears to play a role in eating and drinking behavior. Most urocortin-positive (urocortin(+)) neurons in rodents are found in the cytoarchitecturally defined Edinger-Westphal nucleus (EW). However, the EW is traditionally described as the source of the preganglionic parasympathetic outflow to the ciliary ganglion. We examined the distribution of urocortin(+) cells and motoneurons by use of immunohistochemical staining for this peptide and for choline acetyltransferase (ChAT) in macaque monkeys, in which most preganglionic motoneurons inhabit the EW, and in cats, in which most do not. In both species, lack of overt double labeling indicated that the ChAT(+) and urocortin(+) cells are separate populations. In the monkey, most nonoculomotor ChAT(+) neurons were found within the EW. In contrast, urocortin(+) cells were distributed mainly between the oculomotor nuclei and in the supraoculomotor area. In the cat, most nonoculomotor ChAT(+) cells were located in the supraoculomotor area and anteromedian nucleus. Few were present in the cat EW. Instead, this nucleus was filled with urocortin(+) cells. These results highlight the fact the term EW has come to indicate different nuclei in different species. Consequently, we have adopted the identifiers preganglionic (EW(PG)) and urocortin-containing (EW(U)) to designate the cytoarchitecturally defined EW nuclei in monkeys and cats, respectively. Furthermore, we propose a new open-ended nomenclature for the perioculomotor (pIII) cells groups that have distinctive projections and neurochemical signatures. This will allow more effective scientific discourse on the connections and function of groups such as the periculomotor urocortin (pIII(U)) and preganglionic (pIII(PG)) populations.
Topics: Animals; Autonomic Fibers, Preganglionic; Cats; Choline O-Acetyltransferase; Cholinergic Fibers; Female; Macaca fascicularis; Macaca mulatta; Male; Mesencephalon; Neurons; Parasympathetic Nervous System; Species Specificity; Terminology as Topic; Urocortins
PubMed: 18186029
DOI: 10.1002/cne.21514 -
The Journal of Comparative Neurology Nov 2013Accumulating evidence demonstrates that acetylcholine can directly modulate immune function in peripheral tissues including the spleen and gastrointestinal tract....
Accumulating evidence demonstrates that acetylcholine can directly modulate immune function in peripheral tissues including the spleen and gastrointestinal tract. However, the anatomical relationships between the peripheral cholinergic system and immune cells located in these lymphoid tissues remain unclear due to inherent technical difficulties with currently available neuroanatomical methods. In this study, mice with specific expression of the tdTomato fluorescent protein in choline acetyltransferase (ChAT)-expressing cells were used to label preganglionic and postganglionic cholinergic neurons and their projections to lymphoid tissues. Notably, our anatomical observations revealed an abundant innervation in the intestinal lamina propria of the entire gastrointestinal tract principally originating from cholinergic enteric neurons. The aforementioned innervation frequently approached macrophages, plasma cells, and lymphocytes located in the lamina propria and, to a lesser extent, lymphocytes in the interfollicular areas of Peyer's patches. In addition to the above innervation, we observed labeled epithelial cells in the gallbladder and lower intestines, as well as Microfold cells and T-cells within Peyer's patches. In contrast, we found only a sparse innervation in the spleen consisting of neuronal fibers of spinal origin present around arterioles and in lymphocyte-containing areas of the white pulp. Lastly, a small population of ChAT-expressing lymphocytes was identified in the spleen including both T- and B-cells. In summary, this study describes the variety of cholinergic neuronal and nonneuronal cells in a position to modulate gastrointestinal and splenic immunity in the mouse.
Topics: Acetylcholine; Animals; Antigens, CD; Autonomic Denervation; Choline O-Acetyltransferase; Gastrointestinal Tract; Intestinal Mucosa; Luminescent Proteins; Lymph Nodes; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neuroglia; Neurons; Peyer's Patches; Spleen
PubMed: 23749724
DOI: 10.1002/cne.23376 -
Acta Neuropathologica Mar 2017Detection of α-synuclein lesions in peripheral tissues is a feature of human synucleinopathies of likely pathogenetic relevance and bearing important clinical...
Detection of α-synuclein lesions in peripheral tissues is a feature of human synucleinopathies of likely pathogenetic relevance and bearing important clinical implications. Experiments were carried out to elucidate the relationship between α-synuclein accumulation in the brain and in peripheral organs, and to identify potential pathways involved in long-distance protein transfer. Results of this in vivo study revealed a route-specific transmission of α-synuclein from the rat brain to the stomach. Following targeted midbrain overexpression of human α-synuclein, the exogenous protein was capable of reaching the gastric wall where it was accumulated into preganglionic vagal terminals. This brain-to-stomach connection likely involved intra- and inter-neuronal transfer of non-fibrillar α-synuclein that first reached the medulla oblongata, then gained access into cholinergic neurons of the dorsal motor nucleus of the vagus nerve and finally traveled via efferent fibers of these neurons contained within the vagus nerve. Data also showed a particular propensity of vagal motor neurons and efferents to accrue α-synuclein and deliver it to peripheral tissues; indeed, following its midbrain overexpression, human α-synuclein was detected within gastric nerve endings of visceromotor but not viscerosensory vagal projections. Thus, the dorsal motor nucleus of the vagus nerve represents a key relay center for central-to-peripheral α-synuclein transmission, and efferent vagal fibers may act as unique conduits for protein transfer. The presence of α-synuclein in peripheral tissues could reflect, at least in some synucleinopathy patients, an ongoing pathological process that originates within the brain and, from there, reaches distant organs innervated by motor vagal projections.
Topics: Animals; Autonomic Fibers, Preganglionic; Brain; Choline O-Acetyltransferase; Female; Gastric Mucosa; Green Fluorescent Proteins; Humans; Neurons; Nodose Ganglion; RNA, Messenger; Rats; Rats, Sprague-Dawley; Time Factors; Transduction, Genetic; Vagus Nerve; alpha-Synuclein
PubMed: 28012041
DOI: 10.1007/s00401-016-1661-y