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Brain Research Jun 2018There is mounting evidence underscoring a role for the urothelium in urinary bladder sensation. Previous functional studies have identified bladder primary afferents...
There is mounting evidence underscoring a role for the urothelium in urinary bladder sensation. Previous functional studies have identified bladder primary afferents with mechanosensitive properties suggesting urothelial innervation and/or communication. The current study identifies a group of urothelium-innervating afferent neurons in rat, and characterizes and compares the properties of these and non-urothelial afferent neuron populations. Lumbosacral (LS) primary afferent neurons were retrogradely labeled using intraparenchymal (IPar) microinjection or intravesical (IVes) infusion of tracer into the bladder. Using these techniques, separate populations of neurons were differentiated by dorsal root ganglion (DRG) somata labeling and dye distribution within the bladder. IPar- and IVes-labeled neurons accounted for 85.0% and 14.4% of labeled L6-S1 neurons (P < .001), respectively, with only 0.6% of neurons labeled by both techniques. Following IVes labeling, dye was contained only within the periurothelial bladder region in contrast to non-urothelial distribution of dye after IPar labeling. Electrophysiological characterization by in situ patch-clamp recordings from whole-mount DRG preparations indicated no significant difference in passive or active membrane properties of IPar and IVes DRG neurons. However, calcium imaging of isolated neurons indicates that a greater proportion of IPar- than IVes-labeled neurons express functional TRPA1 (45.7% versus 25.6%, respectively; P < .05). This study demonstrates that two anatomically distinct groups of LS bladder afferents can be identified in rat. Further studies of urothelial afferents and the phenotypic differences between non-/urothelial afferents may have important implications for normal and pathophysiological bladder sensory processing.
Topics: Animals; Calcium; Female; Ganglia, Spinal; Isothiocyanates; Lumbar Vertebrae; Membrane Potentials; Neuroanatomical Tract-Tracing Techniques; Neurons, Afferent; Patch-Clamp Techniques; Peripheral Nervous System Agents; Random Allocation; Rats, Sprague-Dawley; Sacrum; TRPA1 Cation Channel; Urinary Bladder; Urothelium
PubMed: 29291392
DOI: 10.1016/j.brainres.2017.12.023 -
Journal of Neurophysiology Apr 2001Electrical stimulation of vagal afferents or cardiopulmonary sympathetic afferent fibers excites C(1)--C(2) spinal neurons. The purposes of this study were to compare...
Electrical stimulation of vagal afferents or cardiopulmonary sympathetic afferent fibers excites C(1)--C(2) spinal neurons. The purposes of this study were to compare the responses of superficial (depth <0.35 mm) and deeper C(1)--C(2) spinal neurons to noxious chemical stimulation of cardiac afferents and determine the relative contribution of vagal and sympathetic afferent pathways for transmission of noxious cardiac afferent input to C(1)--C(2) neurons. Extracellular potentials of single C(1)--C(2) neurons were recorded in pentobarbital anesthetized and paralyzed male rats. A catheter was placed in the pericardial sac to administer a mixture of algogenic chemicals (0.2 ml) that contained adenosine (10(-3) M), bradykinin, histamine, serotonin, and prostaglandin E(2) (10(-5) M each). Intrapericardial chemicals changed the activity of 20/106 (19%) C(1)--C(2) spinal neurons in the superficial laminae, whereas 76/147 (52%) deeper neurons responded to cardiac noxious input (P < 0.01). Of 96 neurons responsive to cardiac inputs, 48 (50%) were excited (E), 41 (43%) were inhibited (I), and 7 were excited/inhibited (E-I) by intrapericardial chemicals. E or I neurons responsive to intrapericardial chemicals were subdivided into two groups: short-lasting (SL) and long-lasting (LL) response patterns. In superficial gray matter, excitatory responses to cardiac inputs were more likely to be LL-E than SL-E neurons. Mechanical stimulation of the somatic field from the head, neck, and shoulder areas excited 85 of 95 (89%) C(1)--C(2) spinal neurons that responded to intrapericardial chemicals; 31 neurons were classified as wide dynamic range, 49 were high threshold, 5 responded only to joint movement, and no neuron was classified as low threshold. For superficial neurons, 53% had small somatic fields and 21% had bilateral fields. In contrast, 31% of the deeper neurons had small somatic fields and 46% had bilateral fields. Ipsilateral cervical vagotomy interrupted cardiac noxious input to 8/30 (6 E, 2 I) neurons; sequential transection of the contralateral cervical vagus nerve (bilateral vagotomy) eliminated the responses to intrapericardial chemicals in 4/22 (3 E, 1 I) neurons. Spinal transection at C(6)--C(7) segments to interrupt effects of sympathetic afferent input abolished responses to cardiac input in 10/10 (7 E, 3 I) neurons that still responded after bilateral vagotomy. Results of this study support the concept that C(1)-C(2) superficial and deeper spinal neurons play a role in integrating cardiac noxious inputs that travel in both the cervical vagal and/or thoracic sympathetic afferent nerves.
Topics: Afferent Pathways; Animals; Cervical Vertebrae; Denervation; Heart; Male; Neurons, Afferent; Nociceptors; Pericardium; Rats; Rats, Sprague-Dawley; Spinal Cord; Stimulation, Chemical; Vagotomy
PubMed: 11287476
DOI: 10.1152/jn.2001.85.4.1522 -
The Journal of Neuroscience : the... May 2023Dexterous object manipulation depends critically on information about forces normal and tangential to the fingerpads, and also on torque associated with object...
Dexterous object manipulation depends critically on information about forces normal and tangential to the fingerpads, and also on torque associated with object orientation at grip surfaces. We investigated how torque information is encoded by human tactile afferents in the fingerpads and compared them to 97 afferents recorded in monkeys ( = 3; 2 females) in our previous study. Human data included slowly-adapting Type-II (SA-II) afferents, which are absent in the glabrous skin of monkeys. Torques of different magnitudes (3.5-7.5 mNm) were applied in clockwise and anticlockwise directions to a standard central site on the fingerpads of 34 human subjects (19 females). Torques were superimposed on a 2, 3, or 4 N background normal force. Unitary recordings were made from fast-adapting Type-I (FA-I, = 39), and slowly-adapting Type-I (SA-I, = 31) and Type-II (SA-II, = 13) afferents supplying the fingerpads via microelectrodes inserted into the median nerve. All three afferent types encoded torque magnitude and direction, with torque sensitivity being higher with smaller normal forces. SA-I afferent responses to static torque were inferior to dynamic stimuli in humans, while in monkeys the opposite was true. In humans this might be compensated by the addition of sustained SA-II afferent input, and their capacity to increase or decrease firing rates with direction of rotation. We conclude that the discrimination capacity of individual afferents of each type was inferior in humans than monkeys which could be because of differences in fingertip tissue compliance and skin friction. We investigated how individual human tactile nerve fibers encode rotational forces (torques) and compared them to their monkey counterparts. Human hands, but not monkey hands, are innervated by a tactile neuron type (SA-II afferents) specialized to encode directional skin strain yet, so far, torque encoding has only been studied in monkeys. We find that human SA-I afferents were generally less sensitive and less able to discriminate torque magnitude and direction than their monkey counterparts, especially during the static phase of torque loading. However, this shortfall in humans could be compensated by SA-II afferent input. This indicates that variation in afferent types might complement each other signaling different stimulus features possibly providing computational advantage to discriminate stimuli.
Topics: Female; Humans; Torque; Touch; Fingers; Skin; Hand; Mechanoreceptors; Neurons, Afferent
PubMed: 37142429
DOI: 10.1523/JNEUROSCI.1305-22.2023 -
Current Biology : CB Apr 2003The mechanism that allows a sensory neuron to extend its terminal branches along the appropriate fascicle within the CNS turns out to be the same as that which... (Review)
Review
The mechanism that allows a sensory neuron to extend its terminal branches along the appropriate fascicle within the CNS turns out to be the same as that which positioned the fascicle earlier on, and the gene that controls this position is the same as that which determined the neuron's identity.
Topics: Animals; Axons; Central Nervous System; Drosophila; Drosophila Proteins; Larva; Neurons, Afferent; Receptors, Immunologic
PubMed: 12676102
DOI: 10.1016/s0960-9822(03)00196-9 -
The Journal of Physiology Jan 2017Using high-speed videos time-locked with whole-animal electrical recordings, simultaneous measurement of behavioural kinematics and field potential parameters of C-start...
KEY POINTS
Using high-speed videos time-locked with whole-animal electrical recordings, simultaneous measurement of behavioural kinematics and field potential parameters of C-start startle responses allowed for discrimination between short-latency and long-latency C-starts (SLCs vs. LLCs) in larval zebrafish. Apart from their latencies, SLC kinematics and SLC field potential parameters were intensity independent. Increasing stimulus intensity increased the probability of evoking an SLC and decreased mean SLC latencies while increasing their precision; subtraction of field potential latencies from SLC latencies revealed a fixed time delay between the two measurements that was intensity independent. The latency and the precision in the latency of the SLC field potentials were linearly correlated to the latencies and precision of the first evoked action potentials (spikes) in hair-cell afferent neurons of the lateral line. Together, these findings indicate that first spike latency (FSL) is a fast encoding mechanism that can serve to precisely initiate startle responses when speed is critical for survival.
ABSTRACT
Vertebrates rely on fast sensory encoding for rapid and precise initiation of startle responses. In afferent sensory neurons, trains of action potentials (spikes) encode stimulus intensity within the onset time of the first evoked spike (first spike latency; FSL) and the number of evoked spikes. For speed of initiation of startle responses, FSL would be the more advantageous mechanism to encode the intensity of a threat. However, the intensity dependence of FSL and spike number and whether either determines the precision of startle response initiation is not known. Here, we examined short-latency startle responses (SLCs) in larval zebrafish and tested the hypothesis that first spike latencies and their precision (jitter) determine the onset time and precision of SLCs. We evoked startle responses via activation of Channelrhodopsin (ChR2) expressed in ear and lateral line hair cells and acquired high-speed videos of head-fixed larvae while simultaneously recording underlying field potentials. This method allowed for discrimination between primary SLCs and less frequent, long-latency startle responses (LLCs). Quantification of SLC kinematics and field potential parameters revealed that, apart from their latencies, they were intensity independent. We found that increasing stimulus intensity decreased SLC latencies while increasing their precision, which was significantly correlated with corresponding changes in field potential latencies and their precision. Single afferent neuron recordings from the lateral line revealed a similar intensity-dependent decrease in first spike latencies and their jitter, which could account for the intensity-dependent changes in timing and precision of startle response latencies.
Topics: Animals; Animals, Genetically Modified; Behavior, Animal; Female; Hair Cells, Auditory; Larva; Male; Neurons, Afferent; Reaction Time; Reflex, Startle; Rhodopsin; Zebrafish
PubMed: 27228964
DOI: 10.1113/JP272466 -
Neuron May 2001
Review
Topics: Animals; Brain; Drosophila; Mammals; Neurons, Afferent; Odorants; Olfactory Mucosa; Smell
PubMed: 11394992
DOI: 10.1016/s0896-6273(01)00309-9 -
Progress in Neurobiology Nov 2008Insights into the biological basis for mammalian taste quality coding began with electrophysiological recordings from "taste" nerves and this technique continues to... (Review)
Review
Insights into the biological basis for mammalian taste quality coding began with electrophysiological recordings from "taste" nerves and this technique continues to produce essential information today. Chorda tympani (geniculate ganglion) neurons, which are particularly involved in taste quality discrimination, are specialists or generalists. Specialists respond to stimuli characterized by a single taste quality as defined by behavioral cross-generalization in conditioned taste tests. Generalists respond to electrolytes that elicit multiple aversive qualities. Na(+)-salt (N) specialists in rodents and sweet-stimulus (S) specialists in multiple orders of mammals are well characterized. Specialists are associated with species' nutritional needs and their activation is known to be malleable by internal physiological conditions and contaminated external caloric sources. S specialists, associated with the heterodimeric G-protein coupled receptor T1R, and N specialists, associated with the epithelial sodium channel ENaC, are consistent with labeled line coding from taste bud to afferent neuron. Yet, S-specialist neurons and behavior are less specific than T1R2-3 in encompassing glutamate and E generalist neurons are much less specific than a candidate, PDK TRP channel, sour receptor in encompassing salts and bitter stimuli. Specialist labeled lines for nutrients and generalist patterns for aversive electrolytes may be transmitting taste information to the brain side by side. However, specific roles of generalists in taste quality coding may be resolved by selecting stimuli and stimulus levels found in natural situations. T2Rs, participating in reflexes via the glossopharynygeal nerve, became highly diversified in mammalian phylogenesis as they evolved to deal with dangerous substances within specific environmental niches. Establishing the information afferent neurons traffic to the brain about natural taste stimuli imbedded in dynamic complex mixtures will ultimately "crack taste codes."
Topics: Animals; Humans; Nerve Net; Receptors, Cell Surface; Sensory Receptor Cells; Stimulation, Chemical; Taste
PubMed: 18824076
DOI: 10.1016/j.pneurobio.2008.09.003 -
Developmental Neurobiology Mar 2021Recent work has shown that neuregulin-4 (NRG4) is a physiological regulator of the growth of sympathetic axons and CNS dendrites in the developing nervous system. Here,...
Recent work has shown that neuregulin-4 (NRG4) is a physiological regulator of the growth of sympathetic axons and CNS dendrites in the developing nervous system. Here, we have investigated whether NRG4 plays a role in sensory axon growth and the establishment of cutaneous sensory innervation. Imaging early nerve fibers in the well-characterized cutaneous trigeminal territory, the brachial plexus, and thorax revealed very marked and highly significant decreases in nerve fiber length and branching density in Nrg4 embryos compared with Nrg4 littermates. NRG4 promoted neurotrophin-independent sensory axon growth from correspondingly early trigeminal ganglion and DRG neurons in culture but not from enteroceptive nodose ganglion neurons. High levels of Nrg4 mRNA were detected in cutaneous tissues but not in sensory ganglia. Our findings suggest that NRG4 is an important target-derived factor that participates in the establishment of early cutaneous sensory innervation.
Topics: Axons; Nerve Growth Factors; Neuregulins; Neurons; Neurons, Afferent
PubMed: 33369884
DOI: 10.1002/dneu.22803 -
Developmental Biology Nov 2006Signals from target tissues play critical roles in the functional differentiation of neuronal cells, and in their subsequent adaptations to peripheral changes in the... (Review)
Review
Signals from target tissues play critical roles in the functional differentiation of neuronal cells, and in their subsequent adaptations to peripheral changes in the adult. Sensory neurons in the dorsal root ganglia (DRG) provide an excellent model system for the study of signals that regulate the development of neuronal diversity. DRG have been well characterized and contain both neurons that convey information from muscles about limb position, as well as other neurons that provide sensations from skin about pain information. Sensory neurons involved in pain sensation can be distinguished physiologically and antigenically, and one hallmark characteristic is that these neurons contain neuropeptides important for their functions. The transforming growth factor (TGF) beta family member activin A has recently been implicated in neural development and response to injury. During sensory neuron development, peripheral target tissues containing activin or activin itself can regulate pain neuropeptide expression. Long after development has ceased, skin target tissues retain the capacity to signal neurons about changes or injury, to functionally refine synapses. This review focuses on the role of activin as a target-derived differentiative factor in neural development that has additional roles in response to cutaneous injuries in the adult.
Topics: Activins; Animals; Ganglia, Spinal; Humans; Neurons; Neurons, Afferent; Neuropeptides; Nociceptors; Pain; Perception; Signal Transduction; Skin
PubMed: 16973148
DOI: 10.1016/j.ydbio.2006.08.026 -
Biophysical Journal Apr 2017Membrane mechanics is an important biological factor regulating many cellular functions including cell motility, intercellular and intracellular signaling, gene...
Membrane mechanics is an important biological factor regulating many cellular functions including cell motility, intercellular and intracellular signaling, gene expression, and membrane ion channel activity. Primary afferent neurons transduce sensory information about temperature, touch, and pain. These sensory functions may be profoundly affected by the states of primary afferent neuron mechanics. However, membrane mechanics of primary afferent neurons is largely unknown. In this study, we established the optical trapping technique for determining membrane mechanics of cultured primary afferent neurons of the dorsal root ganglia (DRG). We further determined the roles of cytoskeleton and membrane lipids in DRG neuron mechanics. We found that DRG neurons had a plasma membrane tension of ∼54 pN/μm, and the tension was significantly decreased to ∼29 pN/μm by cytochalasin D treatment to disrupt actin cytoskeleton and increased to ∼79 pN/μm by methyl-β-cyclodextrin treatment to sequester membrane cholesterol. DRG neuron membrane stiffness was not significantly affected by the cytoskeleton disruption but was significantly increased after cholesterol sequestration. Our findings elucidate membrane mechanical properties of primary afferent neurons, which provide, to our knowledge, a new perspective on their sensory functions.
Topics: Actins; Animals; Cell Membrane; Cells, Cultured; Cytochalasin D; Cytoskeleton; Elasticity; Female; Ganglia, Spinal; Membrane Lipids; Microscopy, Electron, Scanning; Neurons, Afferent; Optical Tweezers; Peripheral Nervous System Agents; Rats, Sprague-Dawley; beta-Cyclodextrins
PubMed: 28445756
DOI: 10.1016/j.bpj.2017.02.040