Biochemical and morphological characterization of sympathetic neurons grown in a chemically-defined medium

Previous studies have demonstrated that individual neurons from neonatal rat superior cervical ganglion express a mixed adrenergic-cholinergic phenotype when grown under certain tissue culture conditions.^{9,14,15,29,30} The expression of this phenotype is critically influenced by a number of undefined components present in the culture medium.^18,23,33 In the present study, we have examined whether superior cervical ganglion neurons grown on a chemically defined serum-free medium similarly develop dual transmitter expression, or if under these conditions, neurons express only those properties characteristic of their adrenergic heritage. To address this issue, we established that superior cervical ganglion neurons could be maintained in culture for extended periods on the defined medium described by Bottenstein & Sato⁴ in the absence of supporting cells. We then studied the biochemical, immunocytochemical and ultrastructural characteristics of these neurons. We found that in defined medium, superior cervical ganglion neurons continued to express, in a modified form, certain of their expected adrenergic properties, including the development of tyrosine hydroxylase and dopamine-β-hydroxylase activities, stores of endogenous norepinephrine, synaptic vesicles with dense cores and tyrosine hydroxy lase-immunoreactive staining properties. Superior cervical ganglion neurons grown on a defined medium did not, however, acquire cholinergic traits in culture. In this paper we show that choline acetyltransferase activity did not reach detectable levels; the companion paper¹³ documents that cholinergic synapses were not formed.We conclude that superior cervical ganglion neurons, grown under serum-free culture conditions, develop certain properties characteristic of adrenergic neurons and do not express a mixed adrenergic cholinergic phenotype. A companion paper¹³ describes the electrophysiological properties of these neurons and demonstrates the frequent occurrence of electrotonic synapses in these cultures.     

Adenosine triphosphate-evoked currents in cultured dorsal root ganglion neurons obtained from rat embryos: desensitization kinetics and modulation of glutamate release

Sensory neurons express purinergic P2X receptors on their central and peripheral terminals as well as their cell bodies. ATP activation of these receptors drives action potential firing and glutamate release with potentially important consequences for sensory function. Here we show ATP-gated currents activated in cultured embryonic dorsal root ganglion neurons have heterogeneity of time-courses comparable to those observed in different subpopulations of acutely dissociated adult dorsal root ganglion neurons. The distribution of time-courses across the population of cultured neurons is strongly influenced by culture conditions. Heterogeneity in ATP current kinetics occurs even though immunocytochemical staining reveals a relatively homogeneous and widespread expression of the P2X2 and P2X3 subunits. We show that the time-courses of ATP-gated currents recorded at the cell bodies are mirrored by the time-courses of transmitter release from the dorsal root ganglion nerve terminals, indicating similar P2X receptor properties on the soma and their associated terminals.Our results illustrate a functional heterogeneity of P2X receptor-mediated currents that is strongly influenced by external factors. This heterogeneity in current kinetics may have implications for neuronal function as it constrains the time-course of ATP-mediated modulation of neurotransmitter release at sensory nerve terminals.     

AMPA receptor-PDZ interactions in facilitation of spinal sensory synapses.

Silent synapses form between some primary sensory afferents and dorsal horn neurons in the spinal cord. Molecular mechanisms for activation or conversion of silent synapses to conducting synapses are unknown. Serotonin can trigger activation of silent synapses in dorsal horn neurons by recruiting AMPA receptors. AMPA-receptor subunits GluR2 and GluR3 interact via their cytoplasmic C termini with PDZ-domain-containing proteins such as GRIP (glutamate receptor interacting protein), but the functional significance of these interactions is unclear. Here we demonstrate that protein interactions involving the GluR2/3 C terminus are important for serotonin-induced activation of silent synapses in the spinal cord. Furthermore, PKC is a necessary and sufficient trigger for this activation. These results implicate AMPA receptor-PDZ interactions in mechanisms underlying sensory synaptic potentiation and provide insights into the pathogenesis of chronic pain.     

Rapid and modifiable neurotransmitter receptor dynamics at a neuronal synapse in vivo

Synaptic plasticity underlies the adaptability of the mammalian brain, but has been difficult to study in living animals. Here we imaged the synapses between pre- and postganglionic neurons in the mouse submandibular ganglion in vivo, focusing on the mechanisms that maintain and regulate neurotransmitter receptor density at postsynaptic sites. Normally, synaptic receptor densities were maintained by rapid exchange of receptors with nonsynaptic regions (over minutes) and by continual turnover of cell surface receptors (over hours). However, after ganglion cell axons were crushed, synaptic receptors showed greater lateral mobility and there was a precipitous decline in insertion. These changes led to near-complete loss of synaptic receptors and synaptic depression. Disappearance of postsynaptic spines and presynaptic terminals followed this acute synaptic depression. Therefore, neurotransmitter receptor dynamism associated with rapid changes in synaptic efficacy precedes long-lasting structural changes in synaptic connectivity.     

Enkephalin and substance P modulate synaptic properties of chick ciliary ganglion neurons in cell culture

Since enkephalin- and substance P-like immunoreactive materials have been identified in preganglionic terminals of the avian ciliary ganglion, we tested the effects of enkephalin and substance P directly on chick ciliary ganglion neurons in dissociated cell culture. Under these conditions the neurons form cholinergic synapses with each other that are spontaneously active. Both peptides modulate properties of membrane components associated with synaptic transmission between the neurons. Enkephalin causes a 60% reduction in the mean amplitude of the excitatory synaptic potentials, and the effect appears to be presynaptic in origin: enkephalin does not alter acetylcholine sensitivity on the neurons, but does inhibit Ca2+ influx as reflected by a 38% shortening of the Ca2+ component of the action potential. Both the reduction in synaptic potential amplitude and the shortening of the Ca2+ action potential produced by enkephalin are blocked by naloxone. Substance P, on the other hand, has no effect on Ca2+ action potentials but does reduce the time course of acetylcholine responses in the neurons by a mechanism consistent with enhanced receptor desensitization. Decay of the acetylcholine voltage response in the absence of substance P is described by a single exponential process with a time constant of 4-5 s. Coapplication of acetylcholine and substance P results in a second exponential decay process with a time constant of about 1 s that appears after a 200-400 ms lag period. Preincubation with substance P alone does not decrease the peak voltage response or shorten the lag, suggesting that either agonist or activated receptor is necessary for the substance P effect. These findings suggest modulatory roles for the peptides in ganglionic transmission.     

Connecting the ear to the brain: Molecular mechanisms of auditory circuit assembly

Our sense of hearing depends on precisely organized circuits that allow us to sense, perceive, and respond to complex sounds in our environment, from music and language to simple warning signals. Auditory processing begins in the cochlea of the inner ear, where sounds are detected by sensory hair cells and then transmitted to the central nervous system by spiral ganglion neurons, which faithfully preserve the frequency, intensity, and timing of each stimulus. During the assembly of auditory circuits, spiral ganglion neurons establish precise connections that link hair cells in the cochlea to target neurons in the auditory brainstem, develop specific firing properties, and elaborate unusual synapses both in the periphery and in the CNS. Understanding how spiral ganglion neurons acquire these unique properties is a key goal in auditory neuroscience, as these neurons represent the sole input of auditory information to the brain. In addition, the best currently available treatment for many forms of deafness is the cochlear implant, which compensates for lost hair cell function by directly stimulating the auditory nerve. Historically, studies of the auditory system have lagged behind other sensory systems due to the small size and inaccessibility of the inner ear. With the advent of new molecular genetic tools, this gap is narrowing. Here, we summarize recent insights into the cellular and molecular cues that guide the development of spiral ganglion neurons, from their origin in the proneurosensory domain of the otic vesicle to the formation of specialized synapses that ensure rapid and reliable transmission of sound information from the ear to the brain.     

Postnatal rat sympathetic neurons in culture. II. Synaptic transmission by postnatal neurons.

1. It was shown in the preceding paper that postnatally derived rat superior cervical ganglion neurons (SCGN) will grow in dissociated cell culture and form functional synaptic connections with each other. In this report, synaptic transmission by the postnatal SCGN is detailed. 2. Synaptic interactions between SCGN were blocked by the nicotinic cholinergic antagonist hexamathonium (C-6), indicating that acetylcholine was the transmitter substance used by these neurons. This was found to be the case even for neurons taken from 12.5-wk-old animals. 3. In a few cases, the beta-adrenergic blocking agent, propranolol, was found to block synaptic potentials, suggesting that a catecholamine might be involved in the transmission process. The possible mechanisms of this involvement are discussed. 4. SCGN taken from up to 10-wk-old rats were able to form functional synaptic contacts with cocultured skeletal muscle cells. These interactions were sensitive to low external Ca2+ and to 1--2 microM d-tubocurarine (d-TC). 5. It is concluded that even adult SCGN retain a certain amount of neurotransmitter "plasticity" when grown under appropriate culture conditions. From the data on the neuron-neuron and SCGN-skeletal muscle interactions, it is suggested that a matching of presynaptic transmitter with postsynaptic receptor is a sufficient condition for the formation of functional nerve-target interactions.     

Acute destruction of the synaptic ribbon reveals a role for the ribbon in vesicle priming

In vision, balance and hearing, sensory receptor cells translate sensory stimuli into electrical signals whose amplitude is graded with stimulus intensity. The output synapses of these sensory neurons must provide fast signaling to follow rapidly changing stimuli while also transmitting graded information covering a wide range of stimulus intensity and must be able to sustain this signaling for long time periods. To meet these demands, specialized machinery for transmitter release, the synaptic ribbon, has evolved at the synaptic outputs of these neurons. We found that acute disruption of synaptic ribbons by photodamage to the ribbon markedly reduced both sustained and transient components of neurotransmitter release in mouse bipolar cells and salamander cones without affecting the ultrastructure of the ribbon or its ability to localize synaptic vesicles to the active zone. Our results indicate that ribbons mediate both slow and fast signaling at sensory synapses and support an additional role for the synaptic ribbon in priming vesicles for exocytosis at active zones.     

Pattern generation in caudal-lumbar and sacrococcygeal segments of the neonatal rat spinal cord

Glutamate is the major excitatory amino acid neurotransmitter in the CNS, including the neocortex, hippocampus, and spinal cord. Normal synaptic transmission is mainly mediated by glutamate AMPA and/or kainate receptors. Glutamate N-methyl-D-aspartate (NMDA) receptors are normally inactive and only activated when a sufficient postsynaptic depolarization is induced by the activity. Here we show that in sensory synapses of adult mouse, some synaptic responses (26.3% of a total of 38 experiments) between primary afferent fibers and dorsal horn neurons are almost completely mediated by NMDA receptors. Dorsal root stimulation did not elicit any detectable AMPA/kainate receptor-mediated responses in these synapses. Unlike young spinal cord, serotonin alone did not produce any long-lasting synaptic enhancement in adult spinal dorsal horn neurons. However, co-application of the adenylyl cyclase activator forskolin and serotonin (5-HT) produced long-lasting enhancement, including the recruitment of functional AMPA receptor-mediated responses. Calcium-sensitive, calmodulin-regulated adenylyl cyclases (AC1, AC8) are required for the enhancement. Furthermore the thresholds for generating action potential responses were decreased, and, in many cases, co-application of forskolin and 5-HT led to the generation of action potentials by previously subthreshold stimulation of primary afferent fibers in the presence of the NMDA receptor blocker 2-amino-5-phosphonovaleric acid. Our results suggest that pure NMDA synapses exist on sensory neurons in adult spinal cord and that they may contribute to functional sensory transmission. The synergistic recruitment of functional AMPA responses by 5-HT and forskolin provides a new cellular mechanism for glutamatergic synapses in mammalian spinal cord.     

Developmental switch in the polarity of experience-dependent synaptic changes in layer 6 of mouse visual cortex

Layer 6 (L6) of primary sensory cortices is distinct from other layers in that it provides a major cortical input to primary sensory thalamic nuclei. L6 pyramidal neurons in the primary visual cortex (V1) send projections to the lateral geniculate nucleus (LGN), as well as to the thalamic reticular nucleus and higher order thalamic nuclei. Although L6 neurons are proposed to modulate the activity of thalamic relay neurons, how sensory experience regulates L6 neurons is largely unknown. Several days of visual deprivation homeostatically adjusts excitatory synapses in L4 and L2/3 of V1 depending on the developmental age. For instance, L4 exhibits an early critical period during which visual deprivation homeostatically scales up excitatory synaptic transmission. On the other hand, homeostatic changes in L2/3 excitatory synapses are delayed and persist into adulthood. In the present study we examined how visual deprivation affects excitatory synapses on L6 pyramidal neurons. We found that L6 pyramidal neurons homeostatically increase the strength of excitatory synapses following 2 days of dark exposure (DE), which was readily reversed by 1 day of light exposure. This effect was restricted to an early critical period, similar to that reported for L4 neurons. However, at a later developmental age, a longer duration of DE (1 wk) decreased the strength of excitatory synapses, which reversed to normal levels with light exposure. These changes are opposite to what is predicted from the homeostatic plasticity theory. Our results suggest that L6 neurons differentially adjust their excitatory synaptic strength to visual deprivation depending on the age of the animals.     

The dorsal unpaired median neurons of the locust metathoracic ganglion: neuronal structure and diversity, and synapse distribution

Summary Dorsal unpaired median (DUM) neurons are bilaterally symmetrical. A single primary neurite arises from the soma and runs anteriorly through the neuropil before dividing into two lateral neurites which pass to the nerve roots on each side of the ganglion. The primary neurite runs in one of two tracts, one of which lies further from the surface of the ganglion than the other. The primary neurites in the deeper tract belong to DUM1, DUM5 and DUM3,4,5 neurons, and those in the more superficial tract, to DUM3, DUM3,4 and DUM3,4,5 neurons. Previous studies have shown that in the developing embryonic nervous system the primary neurites of DUM neurons can also be observed to lie in one of two tracts, but these do not appear to correspond to those seen in the adult. The results described here differ further from those of other investigations of adult and embryonic locusts in that no DUM4,5 neurons were seen, but DUM3,4 neurons, not found in previous studies, were frequently stained. The secondary neurites of DUM neurons characteristically give rise to fine 0.2–0.5 m diameter processes which may run for hundreds of microns through the neuropil with very little branching. The problems this may pose for signal transmission along such processes is discussed. Presynaptic processes of several types make inputs on to spines on the lateral neurites of DUM neurons and on to branches from secondary neurites. Output synapses were rarely observed and were found only on lateral neurite spines. It therefore appears unlikely that the DUM neurons examined play a major central role within the metathoracic ganglion. A novel structure, with the appearance of a presynaptic density but which was not associated with synaptic vesicles, was found in certain regions of the neurons.     

Peripheral projections of the chick primary sensory neurons expressing gamma-aminobutyric acid immunoreactivity.

The expression of gamma-aminobutyric acid was studied in sensory neurons and peripheral target tissues of the chick dorsal root ganglia by combining immunocytochemistry and electron microscopy. In the chick embryos, the first immunoreaction was observed at embryonic day 12 in 1.4% of ganglion cell bodies. The intensity of immunostaining gradually increased during development and the percentage of immunostained neurons reached an average of 7.3% after hatching. These immunostained cell bodies could be identified as sensory neurons belonging either to some large neurons of the A1 subclass or to a few small neurons of the B1 subclass. The other neuronal cell bodies, corresponding to the A2 and B2 subclasses, as well as the satellite and glial cells were apparently devoid of any gamma-aminobutyric acid immunostaining. Among the peripheral tissues innervated by the primary sensory neurons, the nerve endings of Achilles' tendon and the paravertebral autonomic ganglia appeared devoid of immunoreactivity. In contrast, immunoreactivity was found within nerve endings located in some neuromuscular spindles of the skeletal muscles and within some Herbst's corpuscles in the subcutaneous tissue of the skin. Thus, the present results provide evidence that gamma-aminobutyric acid may be expressed by neuronal cell bodies belonging to two subclasses of primary sensory neurons and could be a putative neurotransmitter involved in the peripheral sensory innervation of, at least in part, skin and skeletal muscles.     

Apoptosis of inner hair cells caused by laser ablation of their spiral ganglion neurons in cultures of the mouse organ of Corti

Laser beam ablation of spiral ganglion neurons was performed in seven organotypic cultures of the newborn mouse cochlea between 5 and 8 days in vitro, with a recovery period of from 18 hours to 3 days. Direct somatic injury (laser or mechanical) inflicted on hair cells does not necessarily cause their death; many of them survive, repair damage and re-establish their neurosensory connections. By contrast, laser irradiation and ablation of their afferent spiral ganglion neurons causes a most spectacular degeneration of sensory cells within 18-48 hours after the insult. Ultrastructurally, the degenerated hair cells-characteristically the inner hair cells-display "dark-cell vacuolar degeneration" that combines the signs of apoptotic death (the peripheral condensation of nuclear chromatin and nuclear pyknosis) with signs of cell edema, vacuolization and necrosis. The ultimate condensation of the cytoplasm gives the dead cells a jet black appearance. The irradiated spiral ganglion neurons die displaying similar pathological characteristics. The extent and locus of inner hair cell degeneration correspond to that of ablated spiral ganglion neurons: ultimately the ablation of one neuron causes degeneration of a single inner hair cell within the closest radial segment of the afferent innervation. The elimination of spiral ganglion neurons by mechanical means does not affect hair cell survival.It is inferred that the laser pulse acts as a stimulus depolarizing the neuronal membrane of the spiral ganglion neurons and their radial fibers and causing the excitotoxic death of their synaptic sensory cells through excessive stimulation of the glutamatergic receptors. Reciprocal pre-and postsynaptic synapses between the afferent dendrites and inner hair cells in culture could possibly serve as entryways of the stimulus. The pathogenesis of this apparent transsynaptically-induced apoptotic death of inner hair cells will be further examined in culture.     

Vesicular Glutamate Transporter Immunoreactivity in the Periodontal Ligament of the Rat Incisor

The distribution of three vesicular glutamate transporter (VGluT) isoforms, VGluT1, VGluT2, and VGluT3, were investigated in the trigeminal ganglion of the periodontal ligament in the rat incisor—a receptive field of trigeminal ganglion neurons. In the trigeminal ganglion, mRNAs for all VGluT isoforms were detected and proteins were observed in the cytoplasm of trigeminal ganglion cells. VGluT1 immunoreactions were localized within the cytoplasm for all sizes of trigeminal neurons, although predominately in medium–large trigeminal neurons. Double‐labeling showed that most VGluT1 contained both VGluT2 and VGluT3. In the periodontal ligament of the incisor, the Ruffini endings, principal periodontal mechanoreceptors, displayed VGluT1 and VGluT2 immunoreactivities. However, lacked immunoreactions for VGluT3. At the electron microscopic level, VGluT1 immunoreactions were localized around the vesicle membranes at the axon terminal of Ruffini endings. The present results indicate that VGluT is expressed in the sensory nerve endings where apparent synapses are not present. Thus, glutamate in the sensory nerve endings is thought to be used in metabotropic functions. This is because glutamate is a general metabolic substrate, and/or acts as a neurotransmitter as proposed in muscle spindles. Anat Rec, 2012. © 2011 Wiley Periodicals, Inc.     

Signaling mechanisms of down-regulation of voltage-activated Ca2+ channels by transient receptor potential vanilloid type 1 stimulation with olvanil in primary sensory neurons

Olvanil ((N-vanillyl)-9-oleamide), a non-pungent transient receptor potential vanilloid type 1 agonist, desensitizes nociceptors and alleviates pain. But its molecular targets and signaling mechanisms are little known. Calcium influx through voltage-activated Ca(2+) channels plays an important role in neurotransmitter release and synaptic transmission. Here we determined the effect of olvanil on voltage-activated Ca(2+) channel currents and the signaling pathways in primary sensory neurons. Whole-cell voltage-clamp recordings were performed in acutely isolated rat dorsal root ganglion neurons. Olvanil (1 microM) elicited a delayed but sustained inward current, and caused a profound inhibition (approximately 60%) of N-, P/Q-, L-, and R-type voltage-activated Ca(2+) channel current. Pretreatment with a specific transient receptor potential vanilloid type 1 antagonist or intracellular application of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid abolished the inhibitory effect of olvanil on voltage-activated Ca(2+) channel current. Calmodulin antagonists (ophiobolin-A and calmodulin inhibitory peptide) largely blocked the effect of olvanil and capsaicin on voltage-activated Ca(2+) channel current. Furthermore, calcineurin (protein phosphatase 2B) inhibitors (deltamethrin and FK-506) eliminated the effect of olvanil on voltage-activated Ca(2+) channel current. Notably, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, calmodulin antagonists, and calcineurin inhibitors each alone significantly increased the amplitude of voltage-activated Ca(2+) channel current. In addition, double immunofluorescence labeling revealed that olvanil induced a rapid internalization of Ca(V)2.2 immunoreactivity from the membrane surface of dorsal root ganglion neurons. Collectively, this study suggests that stimulation of non-pungent transient receptor potential vanilloid type 1 inhibits voltage-activated Ca(2+) channels through a biochemical pathway involving intracellular Ca(2+)-calmodulin and calcineurin in nociceptive neurons. This new information is important for our understanding of the signaling mechanisms of desensitization of nociceptors by transient receptor potential vanilloid type 1 analogues and the feedback regulation of intracellular Ca(2+) and voltage-activated Ca(2+) channels in nociceptive sensory neurons.     

Presence of neuronal nitric oxide synthase in autonomic and sensory ganglion neurons innervating the lacrimal glands of the cat: an immunofluorescent and retrograde tracer double-labeling study

It is generally considered that parasympathetic postganglionic nerve fibers innervating the lacrimal gland (LG) arise from the pterygopalatine ganglion (PPG), while sympathetic and sensory innervations arise from the superior cervical ganglion (SCG) and trigeminal ganglion (TG), respectively. Recently, we reported for the first time that the parasympathetic innervation of the cat LG was also provided by the otic ganglion (OG) and ciliary ganglion (CG), and that the sensory innervation was also provided by the superior vagal ganglion (SVG) and superior glossopharyngeal ganglion (SGG). To determine if nitric oxide (NO) is a neurotransmitter of the autonomic and sensory neurons innervating the LG, we injected the cholera toxin B subunit (CTB) as a retrograde tracer into the cat LG, and used double-labeling fluorescent immunohistochemistry for CTB and nitric oxide synthase (NOS). We found that NOS-/CTB-immunofluorescent double-labeled perikarya were localized in the PPG, OG, TG, SVG and SGG, but not in the CG and SCG. The highest numbers of NOS-/CTB-immunofluorescent double-labeled neurons were found in the PPG and TG. In addition, we examined the presence of nitrergic nerve fibers in the LG using NADPH-d histochemistry and found that a large amount of NADPH-d-stained nerve fibers were distributed around the glandular acini and in the walls of glandular ducts and blood vessels. This study provides the first direct evidence showing that NO may act as a neurotransmitter or modulator involved in the parasympathetic and sensory regulation of lacrimal secretion and blood circulation, but may not be implicated in the sympathetic control of LG activities, and that nitrergic nerve fibers in the LG arise mainly from parasympathetic postganglionic neurons in the PPG and sensory neurons in the TG. The present results suggest that NO plays an important role in the regulation of LG activities.     

Distinct properties of corticothalamic and primary sensory synapses to thalamic neurons

An unique synaptic feature of thalamic relay neurons is that, in addition to receiving primary sensory synapses, they receive massive feedback synapses originating from the cerebral cortex (corticothalamic synapses). These two synapses are both glutamatergic and coordinate the firing responses of thalamic neurons. It has been revealed in the past decade that various glutamate receptors are involved in synaptic responses in the thalamus. However, differences in the compositions of glutamate receptors between corticothalamic and primary sensory synapses have not been fully determined. This update article aims to provide an overview of the differences in the synaptic properties, including the compositions of glutamate receptors, between primary sensory and corticothalamic synapses in the ventrobasal nucleus of the somatosensory thalamus, and then elucidate how these differences in the two synapses influence the firing properties of thalamic neurons.     

Distinct properties of corticothalamic and primary sensory synapses to thalamic neurons

An unique synaptic feature of thalamic relay neurons is that, in addition to receiving primary sensory synapses, they receive massive feedback synapses originating from the cerebral cortex (corticothalamic synapses). These two synapses are both glutamatergic and coordinate the firing responses of thalamic neurons. It has been revealed in the past decade that various glutamate receptors are involved in synaptic responses in the thalamus. However, differences in the compositions of glutamate receptors between corticothalamic and primary sensory synapses have not been fully determined. This update article aims to provide an overview of the differences in the synaptic properties, including the compositions of glutamate receptors, between primary sensory and corticothalamic synapses in the ventrobasal nucleus of the somatosensory thalamus, and then elucidate how these differences in the two synapses influence the firing properties of thalamic neurons.     

Properties of primary sensory (lemniscal) synapses in the ventrobasal thalamus and the relay of high-frequency sensory inputs

The main role of the thalamus is to relay sensory inputs to the neocortex. In the primary somatosensory thalamus (ventrobasal thalamus), sensory inputs deliver tactile information through the medial lemniscus tract. The transmission of sensory information through this pathway is affected by behavioral state. For instance, the relay of high-frequency somatosensory inputs through the thalamus is suppressed during anesthesia or quiescent states but allowed during behaviorally activated states. This change may be due to the effects of modulators on the efficacy of lemniscal synapses. Here I show that lemniscal synapses of adult rodents studied in vitro produce large amplitude-highly secure unitary excitatory postsynaptic potentials (EPSPs), which depress in response to repetitive stimulation at frequencies >2 Hz. Acetylcholine and norepinephrine, which are important thalamic modulators, have no effect on the efficacy of lemniscal EPSPs but reduce evoked inhibitory postsynaptic potentials and corticothalamic EPSPs. Although acetylcholine and norepinephrine do not affect lemniscal synapses, the postsynaptic depolarization they produce on thalamocortical neurons serves to warrant the relay of lemniscal inputs at high-frequency rates by bringing the depressed lemniscal EPSPs close to firing threshold. In conclusion, acetylcholine and norepinephrine released during activated states selectively enhance sensory transmission through the lemniscal pathway by depolarizing thalamocortical neurons and simultaneously depressing the other afferent pathways.     

Expression of leukemia inhibitory factor receptor mRNA in sensory dorsal root ganglion and spinal motor neurons of the neonatal rat

Previous studies have shown that the application of leukemia inhibitory factor to the proximal nerve stump prevents the degeneration of axotomized sensory neurons in the dorsal root ganglion and motor neurons in the spinal cord of newborn rats. This study investigated the expression of leukemia inhibitory factor receptor mRNA in these neurons using in situ hybridization. Leukemia inhibitory factor receptor mRNA was detected both in sensory neurons within the dorsal root ganglion and motor neurons of the cervical spinal cord. Twenty-four hours after axotomy these neurons continue to express leukemia inhibitory factor receptor mRNA. This pattern of leukemia inhibitory factor receptor expression provides a mechanism by which endogenous and exogenous leukemia inhibitory factor could act on injured sensory and motor neurons.