Noradrenalin enhances the activity of cochlear nucleus neurons in the rat

The cochlear nucleus of rats is heavily innervated by noradrenergic fibres from the locus coeruleus. The physiological meaning of this innervation is poorly understood. Therefore, iontophoretically applied noradrenalin was tested on single neurons of the cochlear nucleus in urethane-anaesthetized rats. Iontophoresis of noradrenalin had a dual effect. During application noradrenalin led to moderate inhibition of tone-evoked activity in 37% of the tested neurons. In contrast, approximately 20-30 s after the onset of iontophoresis a long-lasting increase in discharge activity was found in most neurons. Data from iontophoresis of the alpha1-receptor agonist phenylephrine and the alpha2-receptor agonist clonidine suggest that the fast moderate inhibition is mediated by alpha2-receptors while the pronounced long-lasting elevated neuronal firing is mediated by alpha1-receptors. However, these data do not exclude the possibility that part of the response to noradrenalin is also mediated by beta-receptors. Electrical stimulation of the locus coeruleus resulted in an increase in discharge activity comparable with iontophoresis of noradrenalin or phenylephrine. Thus, activation of the locus coeruleus predominantly increases spontaneous and tone-evoked neuronal firing in the cochlear nucleus of the rat. This alpha-receptor-mediated enhanced discharge activity may serve to increase the sensitivity of acoustic processing mechanisms or to lower the threshold for short-latency acoustic reflexes.     

Membrane currents influencing action potential latency in granule neurons of the rat cochlear nucleus

Granule cells are the most numerous neurons in the cochlear nucleus, but, because of their small size, little information on their membrane properties and ionic currents is available. We used an in vitro slice preparation of the rat ventral cochlear nucleus to make whole-cell recordings from these cells. Under current clamp, some granule neurons fired spontaneous action potentials and all generated a train of action potentials on depolarization (threshold current, 10-35 pA). Hyperpolarization increased the latency to the first action potential evoked during a subsequent depolarization. We examined which voltage-gated currents might underlie this latency shift. In addition to a fast inward Na+ current, depolarization activated two outward potassium currents. A transient current was rapidly inactivated by membrane potentials positive to -60 mV, while a second, more slowly inactivating current was observed following the decay of the transient current. No hyperpolarization-activated conductances were observed in these cells. Modelling of the currents suggests that removal of inactivation on hyperpolarization accounts for the increased action potential latency in granule cells. Such a mechanism could account for the 'pauser'-type firing patterns of the fusiform cells which receive a prominent projection from the granule cells in the dorsal cochlear nucleus.     

Degeneration of the dendritic arbor as an index of neurotoxicity in identified catecholamine neurons in rat brain slices

The effect of trace element combination, Béres Drop Plus (BDP) on the immune response of rats following single treatment with cytostatic drug (5-fluorouracil, 5-FU) was tested. Animals were treated with 5-FU and SRBC simultaneously, but separately. Rats were pretreated with BDP for 21 days. The body and spleen weight, furthermore the number of spleen cells and antibody producing cells were determined. The antibody titres in blood serum were also measured. The immune system of rats, 5 days following the 5-FU treatment, showed considerable regeneration. Pretreatment of rats with BDP had a beneficial effect on all parameters investigated.     

Choline acetyltransferase in cochlear root neurons

Cochlear root neurons are a distinct group of cells located in the auditory nerve root in small rodents. Their transmitter is still unknown. Some of our preparations showed immunoreactivity of somata of cochlear root neurons with both polyclonal and monoclonal antibodies against choline acetyltransferase (ChAT) which, despite their very weak histochemical reaction for acetylcholinesterase (AChE), suggested that cochlear root neurons might be cholinergic. To test this, we used a radiometric assay to measure ChAT activities of rat auditory nerve root samples containing cochlear root neurons and of adjacent samples not containing them. There was no significant difference between the low mean ChAT activities of these two groups of samples. Thus, cochlear root neurons are not likely to be cholinergic.     

Ultrastructural and immunocytochemical characterization of neurons in the rat ventral cochlear nucleus projecting to the inferior colliculus

Medium to large-giant multipolar neurons in the rat ventral cochlear nucleus were retrograde labelled after injection of the tracer Wheat Germ Agglutinin conjugated to Horse Radish Peroxidase into the contralateral cochlear nucleus. Light microscopy immunocytochemistry showed that 42.45% of these retrograde labelled neurons, generally strongly labelled with the tracer, were markedly glycine immunopositive, and that 57.55%, usually weakly retrograde labelled neurons, were immunonegative or weakly positive for glycine. These commissural neurons were generally GABA negative and variably immunopositive for glutamate. About 1/3rd of the commissural neurons had variably developed a rough endoplasmic reticulum whilst axo-somatic boutons covered 20-40% of the cell body. These cells were recognized as multipolar neurons of type I. Most of them were weakly glycine positive or even negative and a few appeared glycinergic. A little less than the remaining 2/3rds of the whole commissural population in the postero-ventral cochlear nucleus presented a surface which was 65-85% covered with synaptic boutons, among which some also appeared labelled. These cells were recognized as multipolar neurons of type II. Many microtubules and neurofilaments were present, free ribosomes being more numerous around Nissl bodies with short cisternae. A few low retrograde labelled type II were weakly or non glycinergic. A small number of large to giant neurons type II, strongly retrograde labelled, appeared to be glycine positive, consistently GABA negative and variably glutamate positive. A very small proportion of retrograde labelled neurons appeared having the characteristics of globular bushy neurons. Their weak labelling, however, suggests that they project by collaterals or thin axons to the contralateral cochlear nucleus. Spherical bushy cells in the rat anteroventral cochlear nucleus lack the nuclear capping of rough endoplasmic reticulum observed in the cat, and none was labelled after injection into the contralateral cochlear nucleus. Globular and spherical neurons were variably glutamate positive but glycine and GABA negative. In conclusion, the present study suggests that commissural neurons include a small number of strongly labelled large to giant glycinergic and presumably inhibitory type II and, less frequently type I. A large group of less heavily labelled commissural neurons of type I and II contain low levels or no glycine, which is probably used for metabolic purposes rather than as a neurotransmitter. This suggests that these neurons are presumably excitatory.     

Properties of cochlear nucleus neurons in primary culture

Dissociated primary cell cultures were derived from the cochlear nuclei (CN) of postnatal rats using standard techniques. Cultured cells differentiated morphologically, but their dendritic profiles were generally less specialized than those of CN cells in vivo. Physiologically, cultured cells could be divided into three classes: tonic, phasic and non-spiking cells, which differed in many of their fundamental biophysical properties. The percentage of cultured cells that spiked repetitively increased over time to a maximum of 85% at 6 days. However, the percentage of cells that produced action potentials decreased with time in culture, from 91% during the first 8 days to less than 40% after 9 days. CN cells were successfully cultured in both serum-supplemented and serum-free (Neurobasal) media. More neurons survived at low plating densities in Neurobasal than in medium containing serum, although neuronal survival was similar at higher densities. Few neurons raised in the serum-free medium were spontaneously active; other response properties were similar to those of cells grown in the presence of serum. Although differentiation of CN cells in culture did not completely mirror the in vivo developmental pattern, these experiments demonstrate that primary culture represents a viable method for the in vitro study of CN neurons.     

Degeneration in vivo of rat hippocampal neurons by wild-type Alzheimer amyloid precursor protein overexpressed by adenovirus-mediated gene transfer

In an attempt to elucidate the pathological implications of intracellular accumulation of the amyloid precursor protein (APP) in postmitotic neurons in vivo, we transferred APP695 cDNA into rat hippocampal neurons by using a replication-defective adenovirus vector. We first improved the efficiency of adenovirus-mediated gene transfer into neurons in vivo by using hypertonic mannitol. When a beta-galactosidase-expressing recombinant adenovirus suspended in 1 M mannitol was injected into a dorsal hippocampal region, a number of neurons in remote areas were positively stained, presumably owing to increased retrograde transport of the virus. When an APP695-expressing adenovirus was injected into the same site, part of the infected neurons in the hippocampal formation underwent severe degeneration in a few days, whereas astrocytes near the injection site showed no apparent degeneration. These degenerating neurons accumulated different epitopes of APP, and beta/A4 protein (Abeta)-immunoreactive materials were undetected in the extracellular space. A small number of degenerating neurons showed nuclear DNA fragmentation. Electron microscopic examinations demonstrated that degenerating neurons had shrunken perikarya along with synaptic abnormalities. Microglial cells/macrophages were often found in close proximity to degenerating neurons, and in some cases they phagocytosed these neurons. These results suggest that intracellular accumulation of wild-type APP695 causes a specific type of neuronal degeneration in vivo in the absence of extracellular Abeta deposition.     

Membrane properties of mouse dorsal cochlear nucleus neurons in vitro

Intracellular recordings were made from neurons of the mouse dorsal cochlear nucleus (DCN) in vitro using current clamp techniques in the presence or absence of different ion channel blocking drugs. Four electrophysiologically distinct cell groups were identified in the DCN. The groups were characterized on the basis of their spontaneous firing properties, the shape of the action potential (AP) and the pattern of firing, the shape of the current-voltage (I/V) relationship and the effects of channel blocking agents. By comparison with known histology, three of the four DCN groups were postulated to be cartwheel-like, fusiform-like, or tuberculoventral-like cells. The fourth group was postulated to be a stellate-like as it had similar properties to the spike train (stellate) cell of the AVCN. DCN stellate-like cells were spontaneously active, the action potentials (APs) were always followed by a large, brief hyperpolarization and the cells had linear current voltage relationships. The fusiform-like cells were spontaneously active and spontaneous IPSPs were also observed. The I/V relationship was linear for these cells. Tuberculoventral-like cells were not spontaneously active, but APs could be elicited by inward current injection. The I/V relationships for tuberculoventral-like cells were linear. Cartwheel-like cells were spontaneously active. These cells were characterized by the distinctive shape of their APs which were single, large amplitude, short duration APs sometimes followed by a series of complexes consisting of small, long duration APs. Cartwheel-like cells were the only cell type in the DCN which had non-linear I/V relationships. All cells in the DCN had APs which were abolished by tetrodotoxin. Different calcium dependent channels play a role in the formation of both the fast single AP and the slow complex AP in the cartwheel-like cells since all APs were abolished by the use of high concentrations of verapamil. Verapamil dramatically increased the duration of APs in fusiform-like cells and had no effect on tuberculoventral-like cells. In both tuberculoventral-like cells and cartwheel-like cells, 4-aminopyridine (4AP) depolarized the cells and all APs were abolished. Tetraethylammonium chloride (TEA) had a similar effect in cartwheel-like cells. In stellate-like, tuberculoventral-like and fusiform-like cells, the hyperpolarization which followed the AP was abolished by TEA. The AP duration in these cells was also increased by TEA. 4AP had a similar effect in stellate-like and fusiform-like cells. The data for DCN suggest that electrophysiological properties can be used to distinguish and identify neurons.     

Changes of NADPH-diaphorase activity in the lumbosacral intermediolateral neurons of the rat after pelvic axotomy

Patients with peripheral arterial disease are often perceived to suffer from a disorder whose pathogenesis and symptoms are not amenable to drug therapies. This clinical misperception remains prevalent despite an abundance of data suggesting that diverse pharmacotherapies may modulate the natural history of this disease. Patients with chronic limb arterial occlusive disease suffer from a disease that is characterized by: (1) a prolonged asymptomatic state that can be identified by simple physical examination and confirmed by measurement of the ankle brachial index; (2) a multi-year period of symptomatic claudication; and (3) a variable rate of progression to critical limb ischemia or acute arterial occlusion. This stage-dependent disease progression is mediated via the dynamic, but as yet incompletely understood, interaction of factors that elicit endothelial dysfunction, atherogenesis, and thrombosis. Current data suggest that each of these contributory disease processes can be modulated by extant pharmacotherapies. Additionally, many novel pharmacotherapeutic agents that are currently under investigation may further improve the ability of clinicians to modulate these fundamental biologic processes. Pharmacologic therapies should be targeted to decrease the rate of limb arterial disease progression, to improve limiting symptoms, and to prolong life. Symptoms of claudication can be objectively assessed via both exercise testing and disease-specific questionnaires. The presence of lower extremity atherosclerotic disease is predictive of the presence of coronary heart disease and a foreshortened five-year survival. Current data suggest that clinical investigations should be able to effectively stratify this relative risk via use of both clinical variables (e.g., age, diabetes mellitus, tobacco use, etc.) or by measurement of the ankle brachial index (ABI). The role of the physician is to decrease suffering and to prolong life. Judicious administration of medical therapies can play a critical role in helping the vascular practitioner accomplish these goals.     

Biphasic response of spinal GABAergic neurons after a lumbar rhizotomy in the adult rat

The expression of gamma-aminobutyric acid (GABA) and of the isoforms of the enzyme involved in its synthesis, glutamic acid decarboxylase (GAD), is modified in several rat brain structures in different injury models. The aim of the present work was to determine whether such plasticity of the GABAergic system also occurred in the deafferented adult rat spinal cord, a model where a major reorganization of neural circuits takes place. GABAergic expression following unilateral dorsal rhizotomy was studied by means of non-radioactive in situ hybridization to detect GAD67 mRNA and by immunohistochemistry to detect GAD67 protein and GABA. Three days following rhizotomy the number of GAD67 mRNA-expressing neurons was decreased in the superficial layers of the deafferented horn, while GABA immunostaining of axonal fibres located in this region was highly increased. Seven days after lesion, on the other hand, many GAD67 mRNA-expression neurons were bilaterally detected in deep dorsal and ventral layers, this expression being correlated with the increased detection of GAD67 immunostained somata and with the reduction of GABA immunostaining of axons. GABA immunostaining was frequently found to be associated with reactive astrocytes that exhibited intense immunostaining for glial fibrillary acidic protein (GFAP) but remained GAD67 negative. These results indicate that degeneration of afferent terminals induces a biphasic response of GABAergic spinal neurons located in the dorsal horn and show that many spinal neurons located in deeper regions re-express GAD67, suggesting a possible participation of the local GABAergic system in the reorganization of disturbed spinal networks.     

Computer simulation of shared input among projection neurons in the dorsal cochlear nucleus

Computer simulations of a network model of an isofrequency patch of the dorsal cochlear nucleus (DCN) were run to explore possible mechanisms for the level-dependent features observed in the cross-correlograms of pairs of type IV units in the cat and nominal type IV units in the gerbil DCN. The computer model is based on the conceptual model (of a cat) that suggests two sources of shared input to DCN's projection neurons (type IV units): excitatory input for auditory nerves and inhibitory input from interneurons (type II units). Use of tonal stimuli is thought to cause competition between these sources resulting in the decorrelation of type IV unit activities at low levels. In the model, P-cells (projection neurons), representing type IV units, receive inhibitory input from I-cells (interneurons), representing type II units. Both sets of model neurons receive a simulated excitatory auditory nerve (AN) input from same-CF AN fibers, where the AN input is modeled as a dead-time modified Poisson process whose intensity is given by a computationally tractable discharge rate versus sound pressure level function. Subthreshold behavior of each model neuron is governed by a set of normalized state equations. The computer mode has previously been shown to reproduce the major response properties of both type IV and type II units (e.g., rate-level curves and peri-stimulus time histograms) and the level-dependence of the functional type II-type IV inhibitory interaction. This model is adapted for the gerbil by simulating a reduced population of I-cells. Simulations were carried out for several auditory nerve input levels, and cross-correlograms were computed from the activities of pairs of P-cells for a complete (cat model) and reduced (gerbil model) population of I-cells. The resultant correlograms show central mounds (CMs), indicative of either shared excitatory or inhibitory input, for both spontaneous and tone-evoked driven activities. Similar to experimental results, CM amplitudes are a non-monotonic function of level and CM widths decrease as a function of level. These results are consistent with the hypothesis that shared excitatory input correlates the spontaneous activities of type IV units adn shared inhibitory input correlates their driven activities. The results also suggest that the decorrelation of the activities of type IV units can result from a reduced effectiveness of the AN input as a function of increasing level. Thus, competition between the excitatory and inhibitory inputs is not required.     

Does the organ of Corti attempt to differentiate new hair cells after antibiotic intoxication in rat pups?

In the adult mammalian cochlea, post-injury hair cell losses are considered to be irreversible. Recent studies in cochlear explants of embryonic rodents show that the organ of Corti can replace lost hair cells after injury. We have investigated this topic in vivo during the period of cochlear development. Rat pups were treated with a daily subcutaneous injection of 500 mg/kg amikacin for eight consecutive days between postnatal day 9 (PND 9) and PND 16. During this period the organ of Corti is not fully mature, but hair cells are hyper-sensitive to aminoglycoside antibiotics. Scanning and transmission electron microscopy was used to evaluate morphological changes in the organs of Corti during the treatment and at different post-treatment periods, up until PND 90. A massive loss in outer and inner hair cells was observed at least as early as PND 14. A prominent feature in the apical part of cochleas at PND 21 and 35 was the transient presence of small atypical cells in the region of pre-existing outer hair cells. These atypical cells had tufts of microvilli reminiscent of nascent stereociliary bundles. A second striking observation was the replacement of degenerating inner hair cells by pear-shaped supporting cells throughout the cochlea. These cells were covered with long microvilli, and their basal pole was contacted by both afferent and efferent fibers, as in the early stages of inner hair cell maturation. At PND 55 and 90, these features were not clearly observed due to further cytological changes in the organ of Corti. It is possible that an attempt at hair cell neodifferentiation could occur in vivo after an amikacin treatment in the rat during the period of cochlear hyper-sensitivity to antibiotic.     

Degeneration of axons in the brainstem of the chinchilla after auditory overstimulation

The patterns of axonal degeneration following acoustic overstimulation of the cochlea were traced in the brainstem of adult chinchillas. The Nauta-Rasmussen method for axonal degeneration was used following survivals of 1-32 days after a 105 min exposure to an octave-band noise with a center frequency of 4 kHz and a sound pressure level of 108 dB. Hair-cell and myelinated nerve-fiber loss were assessed in the cochlea. The cochleotopic pattern of terminal degeneration in the ventral cochlear nucleus correlated with the sites of myelinated fiber and inner-hair-cell loss: this correlation was less rigorous with outer-hair-cell loss, especially in the dorsal cochlear nucleus. These results are consistent with a dystrophic process with a slow time course depending on hair-cell loss and/or direct cochlear nerve-fiber damage. However, in a number of cases with no damage in the apical cochlea, fine fiber degeneration occurred with a faster course in low-frequency regions in the dorsal cochlear nucleus and, transynaptically, in a non-cochleotopic pattern in the superior olive and inferior colliculus. These findings suggest that neuronal hyperactivity plays a role in the central degeneration following acoustic overstimulation, possibly by an excitotoxic process.     

Lysosomal changes in rat spinal ganglia neurons after prolonged treatment with cisplatin

We performed morphometric and ultrastructural studies to determine the morphological response of rat spinal ganglion sensory neurons to prolonged administration of cisplatin up to a total dose of 18 mg/kg. We quantitated the different types of lysosomal system (LS) bodies present (primary and secondary lysosomes, lipofuscin granules) as well as multivesicular bodies in treated and control animals. Five rats were examined per group. This ultrastructural study on cisplatin-induced changes in LS of spinal ganglia neurons shows that the total area and total number of LS structures are significantly increased by cisplatin treatment. The main specific changes were increase in number of small-size lysosomes and increase in number of polymeric lipofuscin granules. Other alterations observed were presence of nucleolar segregation, patches of neurofilaments and deposits of osmiophilic material in the perikaryon and axon hillock, all indicating that sensory neurons are a major target of cisplatin.     

Characterization of apoptosis in cultured rat sympathetic neurons after nerve growth factor withdrawal

Sympathetic neurons depend on nerve growth factor (NGF) for their survival both in vivo and in vitro. In culture, the neurons die after NGF withdrawal by an autonomous cell death program but whether these neurons die by apoptosis is under debate. Using vital DNA stains and in situ nick translation, we show here that extensive chromatin condensation and DNA fragmentation occur before plasma membrane breakdown during the death of NGF-deprived rat sympathetic neurons in culture. Furthermore, kinetic analysis of chromatin condensation events within the cell population is consistent with a model which postulates that after NGF deprivation nearly all of the neurons die in this manner. Although the dying neurons display membrane blebbing, cell fragmentation into apoptotic bodies does not occur. Apoptotic events proceed rapidly at around the time neurons become committed to die, regardless of neuronal culture age. However the duration of NGF deprivation required to commit neurons to die, and the rate at which apoptosis occurs, increase with culture age. Thus, within the first week of culture, apoptosis is the predominant form of cell death in sympathetic neurons.     

Speech perception in children after cochlear implantation

Impaired endothelium-dependent vasodilation has been reported to play an important role in the pathogenesis of cardiovascular diseases such as coronary artery disease (CAD) and congestive heart failure (CHF). However, the precise mechanism of endothelial dysfunction has not been elucidated in these conditions. To evaluate the role of oxidative stress in endothelial dysfunction, the effect of antioxidant ascorbic acid on brachial flow-mediated, endothelium-dependent vasodilation during reactive hyperemia and nitroglycerin-induced endothelium-independent vasodilation was examined with high resolution ultrasound in 12 patients with CHF caused by idiopathic dilated cardiomyopathy without established coronary atherosclerosis and in 10 patients with CAD. Flow-mediated vasodilation in CHF (4.4+/-0.5%) and CAD (4.0 - 0.8%) was significantly (p <0.05) attenuated compared with that in 10 control subjects (9.6+/-0.9%). However, nitroglycerin-induced vasodilation was similar in 3 groups (13.7+/-1.3% in control, 13.9+/-1.1% in CHF, 12.7+/-1.4% in CAD). Ascorbic acid could significantly improve flow-mediated vasodilation only in patients with CAD (9.1+/-0.9%) but not with CHF (5.6+/-0.6%), and had no influence on nitroglycerin-induced vasodilation (13.6+/-1.1% in CHF, 14.0+/-1.3% in CAD). These results suggest that, in brachial circulation, augmented oxidative stress mainly leads to endothelial dysfunction in CAD but not in CHF caused by idiopathic dilated cardiomyopathy.     

Effects of somatosensory and parallel-fiber stimulation on neurons in dorsal cochlear nucleus

1. Single units and evoked potentials were recorded in the dorsal cochlear nucleus (DCN) of paralyzed decerebrate cats in response to electrical stimulation at two sites: 1) in the somatosensory dorsal column nuclei (together called MSN below for medullary somatosensory nuclei), which activates mossy-fiber inputs to granule cells in superficial DCN, and 2) on the free surface of the DCN, which activates granule cell axons (parallel fibers) directly. The goal was to evaluate hypotheses about synaptic interactions in the cerebellum-like circuitry of the superficial DCN. A four-pulse facilitation paradigm was used (50-ms interpulse interval); this allows identification of three components of the responses of DCN principal cells (type IV units) to these stimuli. The latencies of the response components were compared with the latency of the evoked potential in DCN, which signals the arrival of the parallel fiber volley at the recording site. 2. The first component is a short-latency inhibitory response; this component is seen only with MSN stimulation and is seen almost exclusively in units also showing the second component, the transient excitatory response. The short-latency inhibitory component precedes the evoked potential. No satisfactory explanation for the short-latency component can be given at present; it most likely reflects a fast-conducting inhibitory input that arrives at the type IV unit before the slowly conducting parallel fibers. 3. The second component is a transient excitatory response; this component is seen with both MSN and parallel fiber stimulation; it is weak and appears to be masked easily by the inhibitory response components. The excitatory component occurs at the same latency as the evoked potential and probably reflects direct excitation of principal cells by granule cell axons. The excitatory component is seen in about half the type IV units for both stimulating sites. With MSN stimulation, the lack of excitation in some units suggests a heterogeneity of cochlear granule cells, with some carrying somatosensory information and some not carrying this information; with parallel fiber stimulation, excitation probably requires the stimulating and recording electrodes to be lined up on the same "beam" of parallel fibers. 4. The third component is a long-lasting inhibitory response that is observed in virtually all type IV units with both MSN and parallel-fiber stimulation; its latency is longer than the evoked potential. Evidence suggests that it is produced by inhibitory input from cartwheel cells. The appearance of this inhibitory component in almost all type IV units can be accounted for by the considerable spread of cartwheel-cell axons in the direction perpendicular to the parallel fibers. 5. The evoked potential and all three components of the unit response vary systematically in size over the four pulses of the electrical stimulus. These results can be accounted for by two phenomena: 1) a facilitation of the granule cell synapses on all cell types that produces a steadily growing response through the four pulses, resembles presynaptic facilitation, and is seen with both MSN and parallel-fiber stimulation; and 2) a strong reduction in the granule cell response between the first and second pulse for MSN stimulation only. This reduction probably occurs presynaptically in the glomerulus or in the granule cell itself and could reflect inhibitory inputs. 6. The response components described above are seen in type IV units recorded in both the fusiform-cell and deep layers of the DCN; this suggests that both pyramidal and giant cells are activated similarly. The simplest interpretation is that both principal cell types are activated by the cerebellum-like circuitry in superficial DCN. Alternatively, because giant cells appear to make limited contact with the granule-cell circuits of superficial DCN, this finding may suggest the existence of currently undescribed granule cell circuits in deep DCN that are si     

Facilitation of acoustic responses of cartwheel neurons of the cat dorsal cochlear nucleus

Responses to clicks were increased in cartwheel cells of the dorsal cochlear nucleus of cats after pairing presentations of the clicks with local iontophoretic delivery of glutamate. The cells were identified by bursting discharges, and were recorded intracellularly in vivo. The findings indicate that inhibitory interneurons such as cartwheel cells can participate in complex adaptive acoustic signal processing. Each cell displayed doublet discharges of > 800 Hz. In 70% of the cells, some of the doublet discharges reached rates > 1000 Hz.     

Trimethyltin intoxication induces marked changes in neuropeptide expression in the rat hippocampus

Stenosis of vessels proximal to the renal artery is an unusual cause of allograft ischemia. We report four patients who had such 'suprarenal' arterial stenoses leading to graft dysfunction that was reversed with revascularization. We additionally review the existing literature on this entity, outline the etiologies of such stenoses, as well as discuss the surgical and non-surgical therapeutic options in patients with this uncommon cause of allograft dysfunction.